Process for hydrocyanation of terminal alkynes
10947186 · 2021-03-16
Assignee
Inventors
Cpc classification
C07B43/00
CHEMISTRY; METALLURGY
C07C253/12
CHEMISTRY; METALLURGY
C07C255/06
CHEMISTRY; METALLURGY
B01J31/2409
PERFORMING OPERATIONS; TRANSPORTING
C07C255/34
CHEMISTRY; METALLURGY
C07C255/31
CHEMISTRY; METALLURGY
C07C253/12
CHEMISTRY; METALLURGY
C07C255/06
CHEMISTRY; METALLURGY
C07C255/31
CHEMISTRY; METALLURGY
C07D333/24
CHEMISTRY; METALLURGY
C07C255/34
CHEMISTRY; METALLURGY
International classification
C07C253/12
CHEMISTRY; METALLURGY
Abstract
The present invention refers to a process for a Rh-catalyzed Anti-Markovnikov hydrocyanation of terminal alkynes which process discloses, for the first time, the highly stereo- and regio-selective hydrocyanation of terminal alkynes to furnish E-configured alkenyl nitriles and the catalyst used in the present process.
Claims
1. A process for hydrocyanation of terminal alkynes comprising reacting a terminal alkyne (I) with at least one CN source selected from the group consisting of HCN and cyanohydrine (II) in the presence of a Rh-complex to obtain an E-alkenyl nitrile (III): ##STR00071## wherein R is i) a straight chain, branched chain or cyclic aliphatic C.sub.1 to C.sub.20 hydrocarbon, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.5 to C.sub.20-heteroaryl, each hydrocarbon optionally being substituted by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.5 to C.sub.20-heteroaryl or heterosubstituents; or ii) SiR.sup.IR.sup.IIR.sup.III, wherein R.sup.I, R.sup.II, and R.sup.III may be same or different and each stands for a straight chain, branched chain or cyclic aliphatic C.sub.1 to C.sub.20 hydrocarbon, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, C.sub.5 to C.sub.20-heteroaryl, (C.sub.1-C.sub.6)-alkyl-C.sub.5 to C.sub.20-heteroaryl, each hydrocarbon optionally being substituted by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.5 to C.sub.20-heteroaryl or heterosubstituents; wherein R.sub.1 and R.sub.2 may be same or different and each stands for a straight chain, branched chain or cyclic aliphatic C.sub.1 to C.sub.20 hydrocarbon, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.5 to C.sub.20-heteroaryl, each hydrocarbon optionally being substituted by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.5 to C.sub.20-heteroaryl or heterosubstituents; wherein cat Rh.sup.I stands for a Tp-Rhodium complex with a mono- or bidentate phosphine, and wherein solvent stands for an organic solvent.
2. Process for hydrocyanation of terminal alkynes according to claim 1, wherein R is a straight chain, branched chain or cyclic aliphatic C.sub.1 to C.sub.20 hydrocarbon, optionally having one or more unsaturated bonds, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, each hydrocarbon optionally being substituted by one or more heterosubstituents.
3. Process for hydrocyanation of terminal alkynes according to claim 1, wherein R.sub.1 and R.sub.2 may be same or different and each stands for is a straight chain, branched chain or cyclic aliphatic C.sub.1 to C.sub.20 hydrocarbon, optionally having one or more unsaturated bonds, C.sub.6 to C.sub.20 aryl, (C.sub.1-C.sub.6)-alkyl-C.sub.6 to C.sub.20-aryl, each hydrocarbon optionally being substituted by one or more heterosubstituents.
4. Process for hydrocyanation of terminal alkynes according to claim 1, wherein cat Rh.sup.I stands for a Tp-Rhodium complex with a bidentate phosphine whereby the residues of the Tp ((tris(1-pyrazolyl)borate anion) and/or the bidentate phosphine ligand are optionally substituted with electro-donating substituent(s).
5. Tp-Rhodium complex with a bidentate phosphine ligand whereby the residues of the Tp ((tris(1-pyrazolyl)borate anion) and/or the bidentate phosphine ligand are optionally substituted with electro-donating substituent(s).
6. Tp-Rhodium complex with a mono- or bidentate phosphine ligand whereby the mono- or bidentate phosphine ligand is selected from dppf (1,1-bis(diphenylphosphino)ferrocene), dppm (1-bis(diphenylphosphino)methane), dppe (bis(diphenylphosphino)ethan), xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene), PCy.sub.3 (tricyclohexylphosphine), PPh.sub.3 (triphenylphosphine), BINAP (2,2 bis(diphenylphosphino)-1,1-binaphthyl), and DPE-phos (bis[2-(diphenylphosphino) phenyl]ether.
7. Tp-Rhodium complex with a bidentate phosphine ligand according to claim 6, which is selected from TpRh(dppf) or TpRh(dpe-phos).
Description
EXPERIMENTAL PART
(1) As shown in the Experimental part, functional groups including esters, halides, ketones, alcohols, trimethylsilyl, pinacolborate, phenols and amides are tolerated in the reaction (Table 1). Both electron-poor and -rich arylacetylenes are suitable substrates. Substitution in the ortho-position of the arenes did not hinder efficient hydrocyanation (2l, 2o). Unprotected anilines yielded less than 5% yield as essayed by GC-MS and NMR spectroscopy, possibly due to amine protonation; however, protected amines as well as amides are tolerated (2h, 2j). Alcohols are also tolerated (2n, 2p). Furthermore, heterocycles such as thiophene (2r) and pyridine (2u) are suitable substrates for the hydrocyanation reaction. Preparation on 1 mmol scale of 2n worked smoothly to give slightly higher yield of product. Within the limits of detection, all products were obtained with complete stereoselectivity, and with complete preference for anti-Markovnikov addition over Markovnikov addition as judged by GC-MS. For example, the inventors have established that in the synthesis of 2g no other volatile compounds, especially no isomer of 2g, are formed.
(2) TABLE-US-00001 TABLE 1 Rh(I)-Catalyzed Anti-Markovnikov Hydrocyanation of Aromatic Terminal Alkynes with Acetone Cyanohydrin.sup.a,b
(3) In addition to hydrocyanation of arylacetylenes, both alkyl- and silyl-substituted alkynes participated in selective hydrocyanation upon modification of the ancillary ligand (DPE-phos instead of dppf) (Table 3). Anti-Markovnikov selectivity was observed here as well, albeit in lower magnitude than what was observed for the aromatic alkynes (4:1-20:1). Both, the alkynyl substituent size and electronic properties influence the regioselectivity. Higher anti-Markovnikov selectivity was obtained with substrates bearing bulkier substituents (5b vs 5c, 5f), and with conjugated enynes (5d vs 5e), which possibly may be explained by faster formation of Rh-vinylidene intermediates (vide infra). Silyl protected acetylene gave product in >20:1 regioselectivity (5g).
(4) TABLE-US-00002 TABLE 3 Rh(I)-Catalyzed Anti-Markovnikov Hydrocyanation of Aliphatic Terminal Alkynes with Acetone Cyanohydrin.sup.a,b
(5) To gain preliminary insight into the mechanism, the inventors observed the formation of the active catalyst TpRh(dppf) upon reaction of dppf and TpRh(COD), which itself was made from commercial [Rh(COD)Cl]2 and KTp..sup.10 Hydrocyanation with TpRh(dppf) as catalyst afforded nearly identical results as compared to the reactions, in which the active catalyst was prepared in situ from TpRh(COD) and dppf (Scheme 2).
(6) ##STR00033##
(7) As detailed above, the present invention refers to a process for the straightforward synthesis of substituted trans acrylonitriles through Rh-catalyzed anti-Markovnikov addition of HCN to terminal alkynes. Mixing of commercially available phenylacetylene, acetone cyanohydrin, dppf and TpRh(COD) (Tp=(tris(1-pyrazolyl)borohydride)) in MeCN and heating at 110 C. afforded the desired cinnamonitrile (2a) in 88% yield, without the formation, within limits of detection, of the Z-isomer or the Markovnikov product (Table 1). Nearly identical results were obtained by using TpRh(C.sub.2H.sub.4).sub.2 instead of TpRh(COD) as catalyst precursor. Because the inventors could prepare TpRh(COD) in higher yield than TpRh(C.sub.2H.sub.4).sub.2, they have opted to use the COD complex in their investigations. The choice of ancillary ligands is crucial for a productive and selective reaction: The Tp ligand is essential; even Tp* (tris(3,5-dimethylpyrazolyl)borohydride)) and Bp (bis(1-pyrazolyl)borohydride) were ineffective. Bidentate diphosphines performed better than monodentate phosphines, the best of which provided only 8% of product. Among the bidentate ligands evaluated, dppf performed best. A reaction temperature of 110 C. is required; no product formed below 70 C.
(8) The invention is further illustrated by the following General Procedures and Examples. The Preparation Examples 1 refer to the preparation of various terminal alkynes which were then reacted to the trans acrylonitriles in the Inventive Examples 2(a-u) and 5.
(9) General Procedure of Hydrocyanation of Arylacetylenes
(10) Under Ar atmosphere, an oven-dried 10 mL vial was charged with TpRh(COD) (31.5 mg, 75.0 mol, 7.50 mol %), dppf (41.5 mg, 75.0 mol, 7.50 mol %) and MeCN (5.0 mL, c=0.2 M). Alkyne (1.00 mmol, 1.00 equiv) and acetone cyanohydrin (85.0 mg, 97.5 L, 1.00 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel to afford the corresponding hydrocyanated alkene.
(11) In situ generation of the catalyst through combination of commercially available [Rh(COD)Cl]2 (3.75 mol), KTp (15 mol), and dppf (7.5 mol) can also be used for productive hydrocyanation. However, the inventors observed that in situ catalyst generation afforded products in lower yield than the use of TpRh(COD) complex. For example, hydrocyanation of phenylacetylene afforded product in 45% yield with the catalyst prepared in situ, while xx % were obtained with TpRh(COD) as precatalyst. For a straightforward synthesis of TpRh(COD) (6), vide infra.
(12) The inventors appreciate that, generally, for practical use, many scientists prefer not to use a glovebox. The transformation, as reported in this general procedure, can be carried out conveniently without the use of a glovebox. For simplicity, in the inventors' own research, the inventors have opted to execute the transformation for most compounds by using a glovebox. Control experiments showed that yields were within error of measurement if the reaction was carried out using a glovebox or not.
(13) General Procedure of Hydrocyanation of Alkylacetylenes
(14) Under Ar atmosphere, an oven-dried 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), DPE-phos (8.0 mg, 15 mol, 7.5 mol %) and MeCN (1.0 mL, c=0.2 M). Alkyne (0.200 mmol, 1.00 equiv.) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv.) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel to afford the corresponding hydrocyanated alkene.
(15) Isomer Analysis
(16) ##STR00034##
(17) The inventors evaluated the selectivity of Markovnikov vs. anti Markovnikov addition, and Z vs. E addition selectivity by GC-MS. To establish that the inventors have chosen an appropriate method to identify the isomers, the inventors provide here a detailed analysis that unambiguously established that for compound 2g, within limits of detection, no other isomers could be detected during or after the reaction. The inventors further show that the isomers are neither destroyed during the reaction, which excludes a reaction with lower selectivity, followed by destruction of the undesired isomers.
(18) Upon complete (>95%) conversion of alkyne 1g, product 2g was isolated in 62% yield. Independent synthesis of Markovnikov isomer 2ga (synthesis, see below) and Z isomer 2gb (synthesis, see below), allowed us to determine the content of 2ga and 2gb during hydrocyanation and after completion to form 2g. GC-MS analysis showed different retention times for all three isomers, respectively: 2g: 5.07 min; 2ga: 4.50 min; 2gb: 4.75 min. No other isomer could be identified, no other product than 2g could be identified by GC MS. GC-MS of the reaction mixture of hydrocyanation of 4-fluorophenylacetylene after 6 h showed a single product peak of the desired product.
2-(4-Fluorophenyl)acrylonitrile (2ga)
(19) ##STR00035##
(20) According to a literature procedure.sup.2, in an anhydrous, argon-filled glovebox, a 20 mL vial was charged with Ni(COD).sub.2 (13.8 mg, 50.0 mol, 5.00 mol %), P(OPh).sub.4 (80.6 mg, 100 mol, 10.0 mol %) and toluene (10.0 mL, c=0.2 M). 4-Fluorophenylacetylene (244 mg, 2.00 mmol, 1.00 equiv.) and acetone cyanohydrin (340 mg, 380 L, 4.00 mmol, 2.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (120 C.). The reaction mixture was then stirred at 120 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:20 (v/v) to afford 14.7 mg (5%) of the title compound as pale yellow crystals.
(21) Rf=0.40 (EtOAc/hexanes 1:10 (v/v)).
(22) NMR Spectroscopy:
(23) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.60-7.58 (m, 2H), 7.14-7.10 (m, 2H), 6.27 (s, 1H), 6.09 (d, J=12 Hz, 1H).
(24) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 156.3 (d, J=242 Hz), 128.7, 128.0 (d, J=8.5 Hz), 127.0 (d, J=2.6 Hz), 122.1, 117.6, 116.3 (d, J=22.3 Hz).
(25) .sup.19F NMR (471 MHz, CDCl.sub.3, 23 C., ): 110.5.
(26) HRMS-FIA (m/z): calc'd for C.sub.9H.sub.6NF [M].sup.+, 147.0479; found: 147.0480.
(Z)-3-(4-Fluorophenyl)acrylonitrile (2gb)
(27) ##STR00036##
(28) According to a literature procedure, to a solution of N-(p-tolylsulfonyl) imine (275 mg, 1.00 mmol, 1.00 equiv.) in acetonitrile (4.0 mL, c=0.25 M) under nitrogen at room temperature was added the nitrile-stabilized phosphonium ylide (361 mg, 1.20 mmol, 1.20 equiv). The mixture was stirred at room temperature for 24 h. The resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:20 (v/v) to afford 14.7 mg (10%) of the title compound as pale yellow crystals.
(29) Rf=0.40 (EtOAc/hexanes 1:10 (v/v)).
(30) NMR Spectroscopy:
(31) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.84-7.81 (m, 2H), 7.15-7.12 (m, 2H), 7.09 (d, J=12 Hz, 1H), 5.43 (d, J=12 Hz, 1H).
(32) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 164.1 (d, J=252 Hz), 147.5 (d, J=1.8 Hz), 131.3 (d, J=7.2 Hz), 130.0 (d, J=3.75 Hz), 117.4, 116.3 (d, J=21.8 Hz), 95.1 (d, J=1.75 Hz).
(33) .sup.19F NMR (471 MHz, CDCl.sub.3, 23 C., ): 107.7.
(34) HRMS-FIA (m/z): calc'd for C.sub.9H.sub.6NF [M].sup.+, 147.0479; found: 147.0481.
(35) ##STR00037##
(36) GC-MS of the hydrocyanation of 4-fluorophenylacetylene with 2ga and 2gb spiking at the beginning of the reaction. The other isomers are not destroyed during the reaction.
(37) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 4-Fluorophenylacethlene (24.0 mg, 23.5 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv), 2-(4-fluorophenyl)acrylonitrile (29.4 mg, 0.200 mmol, 1.00 equiv.) and (Z)-3-(4-fluorophenyl)acrylonitrile (14.7 mg, 0.100 mmol, 1.00 equiv.) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 17.6 mg (60%) title compound as colorless solid. The Markovnikov isomer 2ga and Z isomer 2gb have been found on GC-MS without obvious decomposition. 2ga (26.5 mg, 0.190 mmol) and Z isomer 2gb (14.5 mg, 0.100 mmol) were recovered by flash column chromatography on silica gel.
4-Ethynylbenzamide (1h)
(38) ##STR00038##
(39) Under argon, an oven-dried 25-mL flask was charged with 4-bromobenzamide (0.40 g, 2.0 mmol, 1.0 equiv), Et.sub.3N/THF (2.0 mL, 10:1 (v/v), c=1.0 M), to which PdCl.sub.2(PPh.sub.3).sub.2 (70 mg, 0.10 mmol, 5.0 mol %) and CuI (19 mg, 0.10 mmol, 5.0 mol %) were added. The resulting yellow heterogeneous mixture was cooled to 0 C. in an ice-water bath and stirred at 0 C. for 30 min. Trimethylsilylacetylene (0.39 g, 0.56 mL, 4.0 mmol, 2.0 equiv) was then added within 1 min. Subsequently, the flask was moved from the ice-water bath and heated at 90 C. for 12 h. After cooling to 23 C., the volatiles were evaporated under reduced pressure. The dark oil obtained was diluted by 2.0 mL water and extracted with hexane/Et.sub.2O 10:1 (v/v; 25 mL). The organic phase was collected, dried with Na.sub.2SO.sub.4 and then concentrated under reduced pressure. MeOH (2.0 mL) and K.sub.2CO.sub.3 (0.28 g, 2.0 mmol, 1.0 equiv) were added to the residue, and the resulting mixture was stirred at 23 C. for 2 h. The volatiles were then evaporated under reduced pressure, and the resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:3 (v/v) to afford 154 mg (53%) title product as off-white powder.
(40) Rf=0.25 (EtOAc/hexanes 3:1 (v/v)).
(41) NMR Spectroscopy:
(42) .sup.1H NMR (500 MHz, DMSO-d.sub.6, 23 C., ): 8.10 (br. s, 1H), 7.93-7.91 (m, 2H), 7.60-7.59 (m, 2H), 7.52 (br. s, 1H), 4.38 (s, 1H).
(43) .sup.13C NMR (125 MHz, DMSO-d.sub.6, 23 C., ): 167.1, 134.4, 131.6, 127.8, 124.5, 83.0, 82.7.
(9H-Fluoren-9-yl)-methyl (4-ethynylphenyl)carbamate (1j)
(44) ##STR00039##
(45) Under argon, an oven-dried 20-mL vial was charged 4-alkynylaniline (0.29 g, 2.5 mmol, 1.0 equiv) and anhydrous pyridine (8.0 mL, c=3.2 M). After the reaction mixture was cooled in an ice-water bath (0 C.) for 10 min, FmocCl (0.65 g, 2.5 mmol, 1.0 equiv) was added dropwise within 1 min. The reaction mixture was stirred at 0 C. for 1 h and then at 23 C. for 12 h. The resulting mixture was then acidified with HCl aqueous solution (1.5 mL, c=1.0 M) to pH around 3, and the acidified mixture was extracted with ethyl acetate (EtOAc, 20 mL). The resulting water phase was further extracted with EtOAc (215 mL), and the combined organic phase was subsequently washed with saturated NaHCO.sub.3 aqueous solution (15 mL), followed by brine (15 mL). The organic phase was dried over anhydrous MgSO.sub.4, and the solvent was then evaporated under reduced pressure to afford a brown solid. Further recrystallization from EtOAc (approximately 2.0 mL) afforded 765 mg (90%) of the title compound as yellow powder.
(46) Rf=0.35 (EtOAc/hexanes 1:4 (v/v)).
(47) NMR Spectroscopy:
(48) .sup.1H NMR (500 MHz, DMSO-d.sub.6, 23 C., ): 9.91 (s, 1H), 7.91 (d, J=7.5 Hz, 2H), 7.75 (d, J=7.5 Hz, 2H), 7.47-7.32 (m, 8H), 4.52 (d, J=6.5 Hz, 2H), 4.33 (t, J=6.5 Hz, 1H), 4.05 (s, 1H).
(49) .sup.13C NMR (125 MHz, DMSO-d.sub.6, 23 C., ): 153.7, 144.2, 141.3, 140.1, 132.9, 128.2, 127.6, 125.6, 120.7, 118.5, 115.8, 84.1, 80.1, 66.2, 47.2.
(50) HRMS-ESI (m/z) calc'd for C.sub.23H.sub.17NO.sub.2 [M+Na].sup.+, 362.1152, found: 362.1151.
Methyl 2-ethynylbenzoate (1l)
(51) ##STR00040##
(52) Under argon, an oven-dried 25-mL flask was charged with methyl 2-bromobenzoate (0.43 g, 2.0 mmol, 1.0 equiv) and Et.sub.3N/THF (2.0 mL, 10:1 (v/v), c=1.0 M), to which PdCl.sub.2(PPh.sub.3).sub.2 (70 mg, 0.10 mmol, 5.0 mol %) and CuI (19 mg, 0.10 mmol, 5.0 mol %) were added. The resulting yellow heterogeneous mixture was cooled to 0 C. in an ice-water bath and stirred at 0 C. for 30 min. Trimethylsilylacetylene (0.39 g, 0.56 mL, 4.0 mmol, 2.0 equiv) was then added within 1 min. Subsequently, the flask was moved from the ice-water bath and heated at 90 C. for 12 h. After cooling to 23 C., the volatiles were evaporated under reduced pressure. The dark oil obtained was diluted with 2.0 mL water, and the mixture was extracted with hexane/Et.sub.2O 10:1 (v/v). The organic phase was separated, dried by Na.sub.2SO.sub.4 and then concentrated under reduced pressure. MeOH (2.0 mL) and K.sub.2CO.sub.3 (0.28 g, 2.0 mmol, 1.0 equiv) were added to the residue, and the resulting mixture was stirred at 23 C. for 2 h. The solvent was then evaporated, and the resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 272 mg (55%) of the title compound as yellow oil.
(53) Rf=0.30 (EtOAc/hexanes 1:8 (v/v)).
(54) NMR Spectroscopy:
(55) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.95-7.93 (m, 1H), 7.63-7.61 (m, 1H), 7.49-7.45 (m, 1H), 7.42-7.38 (m, 1H), 3.93 (s, 3H), 3.39 (s, 1H).
(56) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 166.6, 135.1, 132.6, 131.8, 130.4, 128.6, 122.8, 82.4, 82.1, 52.3.
(57) HRMS-EI (m/z) calc'd for C.sub.10H.sub.802 [M].sup.+, 160.0519, found: 160.0520.
5-Ethynyl-6-methoxy-2,3-dihydro-1H-inden-1-one (1 q)
(58) ##STR00041##
(59) Under argon, an oven-dried 25-mL flask was charged with 5-bromo-6-methoxy-2,3-dihydro-1H-inden-1-one (0.48 g, 2.0 mmol, 1.0 equiv) and Et.sub.3N/THF (2.0 mL, 10:1 (v/v), c=1.0 M), to which PdCl.sub.2(PPh.sub.3).sub.2 (70 mg, 0.10 mmol, 5.0 mol %) and CuI (19 mg, 0.10 mmol, 5.0 mol %) were added. The resulting yellow heterogeneous mixture was cooled to 0 C. in an ice-water bath and stirred at 0 C. for 30 min. Trimethylsilylacetylene (0.39 g, 0.56 mL, 4.0 mmol, 2.0 equiv) was then added within 1 min. Subsequently, the flask was moved from the ice-water bath and heated at 90 C. for 12 h. After cooling to 23 C., the volatiles were evaporated under reduced pressure. The dark oil obtained was diluted with 2.0 mL water, and the mixture extracted with hexane-Et.sub.2O 10:1 (v/v). The organic phase was separated, dried by Na.sub.2SO.sub.4 and then concentrated under reduced pressure. MeOH (2.0 mL) and K.sub.2CO.sub.3 (0.28 g, 2.0 mmol, 1.0 equiv) were added to the residue, and the resulting mixture was stirred at 23 C. for 2 h. The solvent was then evaporated, and the resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 6:1 (v/v) to afford 205 mg (55%) of the title compound as colorless oil.
(60) Rf=0.30 (EtOAc/hexanes 1:4 (v/v)).
(61) NMR Spectroscopy:
(62) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.48 (s, 1H), 7.11 (s, 1H), 3.85 (s, 3H), 3.42 (s, 1H), 2.98 (t, J=5.5 Hz, 2H), 2.64 (t, J=5.5 Hz, 2H).
(63) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 206.3, 160.2, 146.8, 138.2, 131.9, 118.5, 103.9, 84.5, 79.6, 56.2, 36.9, 24.8.
(64) HRMS-EI (m/z) calc'd for C.sub.12H.sub.10O.sub.2 [M].sup.+, 186.0676, found: 186.0675.
2-Ethoxy-5-ethynylpyridine (1u)
(65) ##STR00042##
(66) Under argon, an oven-dried 25-mL flask was charged with 5-bromo-2-ethoxypyridine (0.40 g, 2.0 mmol, 1.0 equiv) and Et.sub.3N/THF (2.0 mL, 10:1 (v/v), c=1.0 M), to which PdCl.sub.2(PPh.sub.3).sub.2 (70 mg, 0.10 mmol, 5.0 mol %) and CuI (19 mg, 0.10 mmol, 5.0 mol %) were added. The resulting yellow heterogeneous mixture was cooled to 0 C. in an ice-water bath and stirred at 0 C. for 30 min. Trimethylsilylacetylene (0.39 g, 0.56 mL, 4.0 mmol, 2.0 equiv) was then added within 1 min. Subsequently, the flask was moved from the ice-water bath and heated at 90 C. for 12 h. After cooling to 23 C., the volatiles were evaporated under reduced pressure. The dark oil obtained was diluted by 2.0 mL water, and the mixture extracted with hexane/Et.sub.2O 10:1 (v/v). The organic phase was separated, dried by Na.sub.2SO.sub.4 and then concentrated under reduced pressure. MeOH (2.0 mL) and K.sub.2CO.sub.3 (0.28 g, 2.0 mmol, 1.0 equiv) were added to the residue and the resulting mixture was stirred at 23 C. for 2 h. The solvent was then evaporated and the resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 10:1 (v/v) to afford 212 mg (72%) of the title compound as colorless oil.
(67) Rf=0.25 (EtOAc/hexanes 1:9 (v/v)).
(68) NMR Spectroscopy:
(69) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 8.28 (s, 1H), 7.26 (s, 1H), 6.66 (d, J=8.6 Hz, 1H), 4.36 (q, J=7.0 Hz, 2H), 3.09 (s, 1H), 1.38 (t, J=7.0 Hz, 3H).
(70) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 163.4, 150.8, 141.5, 111.8, 110.8, 80.8, 78.5, 62.1, 14.6.
(71) HRMS-EI (m/z) calc'd for C.sub.9H.sub.9NO [M].sup.+, 147.0679, found: 147.0680.
Cinnamonitrile (2a)
(72) ##STR00043##
(73) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). Phenylacetylene (20.4 mg, 22.0 L, 0.200 mmol, 1.00 equiv) and and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 22.7 mg (88%) of the title compound as pale yellow oil.
(74) Rf=0.45 (EtOAc/hexanes 1:10 (v/v)).
(75) NMR Spectroscopy:
(76) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.45-7.40 (m, 5H), 7.38 (d, J=16.5 Hz, 1H), 5.87 (d, J=16.5 Hz, 1H).
(77) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 150.6, 133.5, 131.2, 129.1, 127.4, 118.2, 96.3.
(78) HRMS-FIA (m/z): calc'd for C.sub.9H.sub.7N [M+Na].sup.+, 152.0471, found: 152.0472.
(E)-3-(4-Methoxyphenyl)acrylonitrile (2b)
(79) ##STR00044##
(80) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 1-Ethynyl-4-methoxybenzene (26.4 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:9 (v/v) to afford 24.8 mg (78%) of the title compound as pale yellow oil.
(81) Rf=0.45 (EtOAc/hexanes 1:19 (v/v)).
(82) NMR Spectroscopy:
(83) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.39 (d, J=8.5 Hz, 2H), 7.33 (d, J=16.5 Hz, 1H), 6.91 (d, J=8.5 Hz, 2H), 5.71 (d, J=16.5 Hz, 1H), 3.85 (s, 3H).
(84) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 162.2, 150.2, 129.2, 126.5, 118.9, 114.7, 93.5, 55.6.
(85) HRMS-FIA (m/z): calc'd for C.sub.10H.sub.9NO [M].sup.+, 159.0679; found: 159.0679.
(E)-3-([1,1-Biphenyl]-4-yl)acrylonitrile (2c)
(86) ##STR00045##
(87) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.5 mL, c=0.13 M). 4-Ethynyl-1,1-biphenyl (35.8 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (20.4 mg, 23.5 L, 0.240 mmol, 1.20 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 28.3 mg (69%) of the title compound as yellow solid.
(88) Rf=0.40 (EtOAc/hexanes 1:10 (v/v)).
(89) NMR Spectroscopy:
(90) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.65-7.60 (m, 4H), 7.54-7.52 (m, 2H), 7.48-7.46 (m, 2H), 7.44 (d, J=16.5 Hz, 1H), 7.41-7.38 (m, 1H), 5.91 (d, J=16.5 Hz, 1H).
(91) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 150.2, 144.2, 139.9, 132.6, 129.1, 128.3, 128.0, 127.9, 127.2, 118.4, 96.2.
(92) HRMS-FIA (m/z): calc'd for C.sub.15H.sub.11N [M].sup.+, 205.0888; found: 205.0886.
(E)-3-(4-(tert-Butyl)phenyl)acrylonitrile (2d)
(93) ##STR00046##
(94) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 1-(tert-Butyl)-4-ethynylbenzene (31.6 mg, 26.5 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 34.0 mg (92%) of the title compound as pale yellow liquid.
(95) Rf=0.45 (EtOAc/hexanes 1:10 (v/v)).
(96) NMR Spectroscopy:
(97) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.44-7.37 (m, 5H), 5.84 (d, J=16.5 Hz, 1H), 1.33 (s, 9H).
(98) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 155.1, 150.6, 131.0, 127.4, 126.2, 118.6, 95.4, 35.1, 31.2.
(99) HRMS-FIA (m/z): calc'd for C.sub.13H.sub.15N [M].sup.+, 185.1199; found: 185.1199.
(100) Gram-Scale Synthesis of 2d
(101) Under Ar atmosphere, an oven-dried 250 mL Schlenk flask was charged with TpRh(COD) (273 mg, 0.650 mmol, 5.00 mol %), dppf (360 mg, 0.650 mmol, 5.00 mol %), and MeCN (50 mL, c=0.26 M) 1-(tert-Butyl)-4-ethynylbenzene (2.05 g, 13.0 mmol, 1.00 equiv) and acetone cyanohydrin (1.10 g, 1.27 mL, 13.0 mmol, 1.00 equiv) were then added to the reaction mixture. The flask was sealed and moved to a preheated oil bath (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel to afford 1.6 g (67%) of the title compound as pale yellow liquid.
(E)-3-(4-(Trimethylsilyl)phenyl)acrylonitrile (2e)
(102) ##STR00047##
(103) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). (4-Ethynylphenyl)trimethylsilane (34.8 mg, 28.0 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (20.4 mg, 23.5 L, 0.240 mmol, 1.20 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 29.3 mg (73%) of the title compound as pale yellow liquid.
(104) Rf=0.50 (EtOAc/hexanes 1:10 (v/v)).
(105) NMR Spectroscopy:
(106) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.57-7.54 (m, 2H), 7.43-7.38 (m, 3H), 5.91 (d, J=16.5 Hz, 1H), 0.29 (s, 9H).
(107) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 150.8, 145.2, 134.2, 133.9, 126.6, 118.4, 96.5, 1.2.
(108) HRMS-FIA (m/z): calc'd for C.sub.12H.sub.15NSi [M].sup.+, 201.0967; found: 201.0968.
(E)-3-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylonitrile (2f)
(109) ##STR00048##
(110) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 2-(4-Ethynylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (45.6 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (20.4 mg, 23.5 L, 0.240 mmol, 1.20 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 34.7 mg (68%) of the title compound as pale yellow liquid.
(111) Rf=0.35 (EtOAc/hexanes 1:10 (v/v)).
(112) NMR Spectroscopy:
(113) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.85 (d, J=8.0 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 7.43 (d, J=16.5 Hz, 1H), 5.96 (d, J=16.5 Hz, 1H), 1.37 (s, 12H).
(114) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 150.5, 135.8, 135.4, 126.5, 118.1, 97.2, 84.2, 24.9.
(115) HRMS-FIA (m/z) calc'd for C.sub.15H.sub.18NO.sub.2 [M+Na].sup.+, 278.1323; found: 278.1324.
(E)-3-(4-Fluorophenyl)acrylonitrile (2q)
(116) ##STR00049##
(117) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 4-Fluorophenylacetylene (24.0 mg, 23.5 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 18.2 mg (62%) of the title compound as colorless solid.
(118) Rf=0.45 (EtOAc/hexanes 1:10 (v/v)).
(119) NMR Spectroscopy:
(120) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.47-7.44 (m, 2H), 7.36 (d, J=16.5 Hz, 1H), 7.12-7.09 (m, 2H), 5.81 (d, J=16.5 Hz, 1H).
(121) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 164.6 (d, J=253.5 Hz), 149.4, 129.9 (d, J=3.1 Hz), 129.5 (d, J=8.8 Hz), 118.1, 116.5 (d, J=22.0 Hz), 96.3.
(122) .sup.19F NMR (471 MHz, CDCl.sub.3, 23 C., ): 107.8.
(123) HRMS-FIA (m/z): calc'd for C.sub.9H.sub.6NF [M].sup.+, 147.0479; found: 147.0481.
(E)-4-(2-Cyanovinyl)benzamide (2h)
(124) ##STR00050##
(125) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.5 mL, c=0.13 M). 4-Ethynylbenzamide (29.0 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 2:1 (v/v) to afford 17.5 mg (51%) of the title compound as colorless solid.
(126) Rf=0.25 (EtOAc/hexanes 2:1 (v/v)).
(127) NMR Spectroscopy:
(128) .sup.1H NMR (500 MHz, DMSO-d.sub.6, 23 C., ): 8.05 (br. s, 1H), 7.92-7.89 (m, 2H), 7.74-7.69 (m, 3H), 7.49-7.47 (br. m, 1H), 6.58 (d, J=16.5 Hz, 1H).
(129) .sup.13C NMR (125 MHz, DMSO-d.sub.6, 23 C., ): 167.5, 150.1, 136.7, 128.5, 128.1, 127.2, 119.1, 98.9.
(130) HRMS-FIA (m/z) calc'd for C.sub.10H.sub.7N.sub.2O [MH].sup., 171.0564; found: 171.0564.
(E)-4-(2-Cyanovinyl)benzonitrile (2i)
(131) ##STR00051##
(132) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 4-Ethynylbenzonitrile (25.4 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:9 (v/v) to afford 20.9 mg (68%) of the title compound as yellow solid.
(133) Rf=0.35 (EtOAc/hexanes 1:9 (v/v)).
(134) NMR Spectroscopy:
(135) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.72-7.70 (m, 2H), 7.57-7.55 (m, 2H), 7.42 (d, J=16.5 Hz, 1H), 6.00 (d, J=16.5 Hz, 1H).
(136) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 148.2, 137.5, 132.9, 127.8, 118.0, 117.1, 114.5, 100.3
(137) HRMS-FIA (m/z) calc'd for C.sub.10H.sub.6N.sub.2 [M].sup.+, 154.0525; found: 154.0525.
(9H-Fluoren-9-yl)methyl (E)-(4-(2-cyanovinyl)phenyl)carbamate (2i)
(138) ##STR00052##
(139) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.5 mL, c=0.13 M). (9H-Fluoren-9-yl)methyl (4-ethynylphenyl)carbamate (67.8 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:4 (v/v) to afford 47.6 mg (65%) of the title compound as pale yellow solid.
(140) Rf=0.35 (EtOAc/hexanes 1:4 (v/v)).
(141) NMR Spectroscopy:
(142) .sup.1H NMR (500 MHz, DMSO-d.sub.6, 23 C., ): 10.02 (br. s, 1H), 7.91 (d, J=7.5 Hz, 2H), 7.75 (d, J=7.5 Hz, 2H), 7.59-7.53 (m, 5H), 7.43 (dd, J=7.5 Hz, 7.5 Hz, 2H), 7.36 (dd, J=7.5 Hz, 7.5 Hz, 2H), 6.29 (d, J=16.5 Hz, 1H), 4.53 (d, J=6.0 Hz, 2H), 4.32 (t, J=6.0 Hz, 1H).
(143) .sup.13C NMR (125 MHz, DMSO-d.sub.6, 23 C., ): 153.2, 150.1, 143.7, 141.7, 140.8, 128.7, 128.0, 127.1, 125.1, 120.2, 119.2, 118.1, 94.3.
(144) HRMS-FIA (m/z) calc'd for C.sub.24H.sub.18N.sub.2O.sub.2Na [M+Na].sup.+, 389.1259; found: 389.1260.
(145) Note: 17% (11.5 mg) of alkyne were recovered by flash column chromatography.
(E)-3-(o-Tolyl)acrylonitrile (2k)
(146) ##STR00053##
(147) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 1-Ethynyl-2-methylbenzene (23.2 mg, 21.2 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 22.6 mg (79%) of the title compound as pale yellow liquid.
(148) Rf=0.45 (EtOAc/hexanes 1:10 (v/v)).
(149) NMR Spectroscopy:
(150) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.70 (d, J=16.5 Hz, 1H), 7.46 (d, J=7.4 Hz, 1H), 7.33 (dd, J=8.1, 7.4 Hz, 1H), 7.23 (dd, J=7.7, 7.4 Hz, 2H), 5.80 (d, J=16.5 Hz, 1H), 2.41 (s, 3H).
(151) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 148.4, 137.2, 132.5, 131.0, 130.9, 126.6, 125.5, 118.3, 97.2, 19.6.
(152) HRMS-FIA (m/z) calc'd for C.sub.10H.sub.9N [M].sup.+, 143.0732; found: 143.0729.
Methyl (E)-2-(2-cyanovinyl)benzoate (2l)
(153) ##STR00054##
(154) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). Methyl 2-ethynylbenzoate (32.0 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:6 (v/v) to afford 29.1 mg (78%) of the title compound as yellow solid.
(155) Rf=0.40 (EtOAc/hexanes 1:6 (v/v)).
(156) NMR Spectroscopy:
(157) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 8.31 (d, J=16.5 Hz, 1H), 8.01 (dd, J=7.5, 1.5 Hz, 1H), 7.57-7.49 (m, 3H), 5.77 (d, J=16.5 Hz, 1H), 3.94 (s, 3H).
(158) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 166.8, 150.2, 135.5, 132.8, 131.3, 130.4, 129.3, 127.4, 117.9, 99.2, 52.7.
(159) HRMS-FIA (m/z) calc'd for C.sub.11H.sub.9NO.sub.2 [M].sup.+, 187.0627; found: 187.0628.
(E)-3-(2-Chlorophenyl)acrylonitrile (2m)
(160) ##STR00055##
(161) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 1-Chloro-2-ethynylbenzene (27.2 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 21.8 mg (67%) of the title compound as yellow solid.
(162) Rf=0.40 (EtOAc/hexanes 1:10 (v/v)).
(163) NMR Spectroscopy:
(164) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.84 (d, J=16.5 Hz, 1H), 7.54 (dd, J=8.0, 1.5 Hz, 1H), 7.44 (dd, J=8.0, 1.5 Hz, 1H), 7.37 (ddd, J=7.6, 7.4, 1.5 Hz, 1H), 7.31 (ddd, J=7.6, 7.4, 1.5 Hz, 1H), 5.91 (d, J=16.5 Hz, 1H).
(165) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 146.6, 134.5, 132.0, 131.8, 130.4, 127.3, 126.9, 117.7, 98.9.
(166) HRMS-FIA (m/z) calc'd for C.sub.9H.sub.6NCl [M].sup.+, 163.0182; found: 163.0183.
(E)-3-(2-(Hydroxymethyl)phenyl)acrylonitrile (2n)
(167) ##STR00056##
(168) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). (2-Ethynylphenyl)methanol (26.4 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:4 (v/v) to afford 20.7 mg (65%) of the title compound as pale yellow liquid.
(169) Rf=0.25 (EtOAc/hexanes 1:4 (v/v)).
(170) NMR Spectroscopy:
(171) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.75 (d, J=16.5 Hz, 1H), 7.44 (d, J=7.6 Hz, 1H), 7.36-7.32 (m, 2H) 7.28 (m, 1H), 5.80 (d, J=16.5 Hz, 1H), 4.65 (s, 2H), 2.21 (s, 1H).
(172) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 148.1, 139.0, 132.6, 131.1, 129.3, 128.6, 126.2, 118.3, 98.1, 62.9.
(173) HRMS-FIA (m/z) calc'd for C.sub.10H.sub.23NO [M+Na].sup.+, 182.0576, found: 182.0577.
(E)-3-Mesitylacrylonitrile (2o)
(174) ##STR00057##
(175) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.5 mL, c=0.13 M). 2-Ethynyl-1,3,5-trimethylbenzene (28.8 mg, 26.5 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (20.4 mg, 23.5 L, 0.240 mmol, 1.20 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 28.1 mg (82%) of the title compound as colorless solid.
(176) Rf=0.50 (EtOAc/hexanes 1:10 (v/v)).
(177) NMR Spectroscopy:
(178) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.58 (d, J=17.0 Hz, 1H), 6.93 (s, 2H), 5.56 (d, J=17.0 Hz, 1H), 2.34 (s, 6H), 2.32 (s, 3H).
(179) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 149.6, 139.4, 136.6, 130.1, 129.5, 118.2, 101.5, 21.1, 21.0.
(180) HRMS-FIA (m/z) calc'd for C.sub.12H.sub.13N [M].sup.+, 171.1043; found: 171.1042.
(E)-3-(3-Hydroxyphenyl)acrylonitrile (2p)
(181) ##STR00058##
(182) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M) 3-Ethynylphenol (23.6 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:2 (v/v) to afford 22.6 mg (78%) of the title compound as colorless solid.
(183) Rf=0.35 (EtOAc/hexanes 1:2 (v/v)).
(184) NMR Spectroscopy:
(185) .sup.1H NMR (500 MHz, CD.sub.3CN, 23 C., ): 7.43 (d, J=16.5 Hz, 1H), 7.26 (dd, J=8.0 Hz, 8.0 Hz, 1H), 7.20 (br. s, 1H), 7.03 (d, J=8.0 Hz, 1H), 6.97 (s, 1H), 6.90 (dd, J=8.0 Hz, 2.5 Hz, 1H), 6.04 (d, J=16.5 Hz, 1H).
(186) .sup.13C NMR (125 MHz, CD.sub.3CN, 23 C., ): 158.3, 151.3, 136.3, 131.2, 120.3, 119.3, 119.1, 114.6, 97.6.
(187) HRMS-FIA (m/z) calc'd for C.sub.9H.sub.7NO [M].sup.+, 145.0525; found: 145.0522.
(E)-3-(6-Methoxy-1-oxo-2,3-dihydro-1H-inden-5-yl)acrylonitrile (2q)
(188) ##STR00059##
(189) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 5-Ethynyl-6-methoxy-2,3-dihydro-1H-inden-1-one (33.2 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:8 (v/v) to afford 27.3 mg (64%) of the title compound as colorless solid.
(190) Rf=0.50 (EtOAc/hexanes 1:8 (v/v)).
(191) NMR Spectroscopy:
(192) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.67 (d, J=16.8 Hz, 1H), 7.49 (s, 1H), 7.23 (s, 1H), 6.15 (d, J=16.8 Hz, 1H), 3.92 (s, 3H), 3.09 (t, J=11.2 Hz, 2H), 2.73 (t, J=11.2 Hz, 2H).
(193) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 206.3, 157.8, 146.9, 145.6, 139.7, 129.1, 126.3, 118.3, 104.8, 100.1, 56.0, 36.9, 25.0.
(194) HRMS-FIA (m/z) calc'd for C.sub.13H.sub.11NO.sub.2Na [M+Na].sup.+, 236.0682; found: 236.0683.
(E)-3-(Thiophen-3-yl)acrylonitrile (2r)
(195) ##STR00060##
(196) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M) 3-Ethynylthiophene (21.6 mg, 22.0 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:9 (v/v) to afford 18.9 mg (70%) of the title compound as yellow liquid.
(197) Rf=0.45 (EtOAc/hexanes 1:9 (v/v)).
(198) NMR Spectroscopy:
(199) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.53-7.52 (m, 1H), 7.42-7.39 (m, 2H), 7.27-7.26 (m, 1H), 5.72 (d, J=16.5 Hz, 1H).
(200) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 144.1, 136.8, 128.7, 127.8, 124.3, 118.4, 95.8.
(201) HRMS-FIA (m/z) calc'd for C.sub.7H.sub.5NSNa [M+Na].sup.+, 158.0034; found: 158.0036.
(E)-3-(Naphthalen-1-yl)acrylonitrile (2s)
(202) ##STR00061##
(203) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.5 mL, c=0.13 M). 1-Ethynylnaphthalene (30.4 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (20.4 mg, 23.5 L, 0.240 mmol, 1.20 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 25.1 mg (70%) of the title compound as yellow liquid.
(204) Rf=0.45 (EtOAc/hexanes 1:10 (v/v)).
(205) NMR Spectroscopy:
(206) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 8.25 (d, J=16.5 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 7.95 (d, J=8.5 Hz, 1H), 7.90 (d, J=7.5 Hz, 1H), 7.68 (d, J=7.5 Hz, 1H), 7.62 (t, J=8.0 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.50 (d, J=7.5 Hz, 1H), 5.98 (d, J=16.5 Hz, 1H).
(207) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 148.1, 133.8, 131.7, 131.1, 130.9, 129.1, 127.6, 126.7, 125.5, 124.8, 123.0, 118.4, 99.0.
(208) HRMS-FIA (m/z) calc'd for C.sub.13H.sub.9N [M].sup.+, 179.0731; found: 179.0729.
(E)-3-(6-Methoxynaphthalen-2-yl)acrylonitrile (2t)
(209) ##STR00062##
(210) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.5 mL, c=0.13 M). 2-Ethynyl-6-methoxynaphthalene (36.4 mg, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (20.4 mg, 23.5 L, 0.240 mmol, 1.20 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:9 (v/v) to afford 30.9 mg (74%) of the title compound as yellow solid.
(211) Rf=0.25 (EtOAc/hexanes 1:9 (v/v)).
(212) NMR Spectroscopy:
(213) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.73-7.66 (m, 3H), 7.48 (dd, J=8.9, 2.5 Hz, 1H), 7.44 (d, J=16.5 Hz, 1H), 7.16 (dd, J=8.9, 2.5 Hz, 1H), 7.10 (d, J=2.5 Hz, 1H), 5.86 (d, J=16.5 Hz, 1H), 3.91 (s, 3H).
(214) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 159.2, 150.7, 136.1, 130.3, 129.5, 128.9, 128.4, 127.8, 122.9, 119.9, 118.6, 106.0, 94.9, 55.4.
(215) HRMS-FIA (m/z) calc'd for C.sub.14H.sub.11NO [M].sup.+, 209.0837; found 209.0835.
(E)-3-(6-Ethoxypyridin-3-yl)acrylonitrile (2u)
(216) ##STR00063##
(217) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), dppf (8.3 mg, 15 mol, 7.5 mol %), and MeCN (1.0 mL, c=0.2 M). 2-Ethoxy-5-ethynylpyridine (29.4 mg, 22.5 L, 0.200 mmol, 1.00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:10 (v/v) to afford 25.1 mg (72%) of the title compound as yellow liquid.
(218) Rf=0.20 (EtOAc/hexanes 1:10 (v/v)).
(219) NMR Spectroscopy:
(220) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 8.18 (d, J=2.5 Hz, 1H), 7.68 (dd, J=8.7, 2.5 Hz, 1H), 7.33 (d, J=16.5 Hz, 1H), 6.75 (d, J=8.7 Hz, 1H), 5.74 (d, J=16.5 Hz, 1H), 4.39 (q, J=7.1 Hz, 3H), 1.39 (t, J=7.1 Hz, 3H).
(221) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 165.6, 148.1, 147.0, 135.4, 122.9, 118.11, 111.9, 94.8, 62.5, 14.5.
(222) HRMS-FIA (m/z) calc'd for C.sub.10H.sub.11N.sub.2O [M+H].sup.+, 175.0866; found: 175.0868.
(E)-6-Phenylhex-2-enenitrile (5a)
(223) ##STR00064##
(224) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), DPE-phos (8.0 mg, 15 mol, 7.5 mol %) and MeCN (1.0 mL, c=0.2 M). 5-Phenyl-1-pentyne (28.8 mg, 32.0 L, 0.200 mmol, 1.00 equiv.) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv.) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue were purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:20 (v/v) to afford 20.8 mg (61%) of the title compound as colorless oil.
(225) Rf=0.20 (EtOAc/hexanes 1:20 (v/v)).
(226) NMR Spectroscopy:
(227) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.31-7.28 (m, 2H), 7.22-7.19 (m, 1H), 7.17-7.15 (m, 2H), 6.71 (dt, J=16.5 Hz, 5.0 Hz, 1H), 5.32 (d, J=16.5 Hz, 1H), 2.64 (t, J=5.0 Hz, 2H), 2.27-2.22 (m, 2H), 1.81-1.77 (m, 2H).
(228) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 155.7, 141.2, 128.6, 128.5, 126.2, 117.6, 100.2, 35.1, 32.8, 29.3.
(229) HRMS-FIA (m/z) calc'd for C.sub.12H.sub.13N [M+Na].sup.+, 194.0941; found: 194.0940.
(E)-Non-2-enenitrile (5b)
(230) ##STR00065##
(231) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), DPE-phos (8.0 mg, 15 mol, 7.5 mol %) and MeCN (1.0 mL, c=0.2 M). 1-Octyne (22.0 mg, 29.5 L, 0.200 mmol, 1.00 equiv.) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv.) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue were purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:20 (v/v) to afford 17.8 mg (65%) of the title compound as colorless oil.
(232) Rf=0.20 (EtOAc/hexanes 1:20 (v/v)).
(233) NMR Spectroscopy:
(234) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 6.71 (dt, J=16.5 Hz, 5.0 Hz, 1H), 5.32 (dt, J=16.5 Hz, 1.5 Hz, 1H), 2.23-2.19 (m, 2H), 1.45-1.42 (m, 2H), 1.32-1.25 (m, 6H), 0.88 (t, J=5.0 Hz, 3H).
(235) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 156.3, 117.7, 99.7, 33.5, 31.6, 28.8, 27.7, 22.6, 14.1.
(236) HRMS-FIA (m/z) calc'd for C.sub.9H.sub.15N [M+Na].sup.+, 160.1097; found: 160.1097.
(E)-3-Cyclohexylacrylonitrile (5d)
(237) ##STR00066##
(238) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), DPE-phos (8.0 mg, 15 mol, 7.5 mol %) and MeCN (1.0 mL, c=0.2 M). Ethynylcyclohexane (21.6 mg, 23.5 L, 0.200 mmol, 1.00 equiv.) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv.) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue were purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:20 (v/v) to afford 15.1 mg (56%) of the title compound as colorless oil.
(239) Rf=0.20 (EtOAc/hexanes 1:20 (v/v)).
(240) NMR Spectroscopy:
(241) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 6.70-6.65 (m, 1H), 5.25 (d, J=16.5 Hz, 1H), 2.17-2.12 (m, 1H), 1.79-1.67 (m, 5H), 1.35-1.11 (m, 5H).
(242) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 161.0, 118.1, 97.7, 41.6, 31.4, 25.8, 25.6.
(243) HRMS-FIA (m/z) calc'd for C.sub.9H.sub.13N [M+Na].sup.+, 158.0941; found: 158.0940.
(E)-3-(Cyclohex-1-en-1-yl)acrylonitrile (5e)
(244) ##STR00067##
(245) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), DPE-phos (8.0 mg, 15 mol, 7.5 mol %) and MeCN (1.0 mL, c=0.2 M). 1-Ethynylcyclohex-1-ene (21.2 mg, 3.5 L, 0.200 mmol, 1.00 equiv.) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv.) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue were purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:20 (v/v) to afford 17.5 mg (65%) of the title compound as colorless oil.
(246) Rf=0.20 (EtOAc/hexanes 1:20 (v/v)).
(247) NMR Spectroscopy:
(248) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 6.99 (d, J=16.5 Hz, 1H), 6.15 (t, J=7.5 Hz, 1H), 5.18 (d, J=16.5 Hz, 1H), 2.23 (br. s, 2H), 2.08 (br. s, 2H), 1.72-1.67 (m, 2H), 1.64-1.61 (m, 2H).
(249) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 153.8, 140.1, 134.8, 119.2, 92.5, 26.5, 23.5, 21.9, 21.9.
(250) HRMS-FIA (m/z) calc'd for C.sub.9H.sub.11N [M].sup.+, 133.0886; found: 133.0886.
(E)-3-(Triisopropylsilyl)acrylonitrile (5q)
(251) ##STR00068##
(252) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol %), DPE-phos (8.0 mg, 15 mol, 7.5 mol %) and MeCN (1.0 mL, c=0.2 M). Ethynyltriisopropylsilane (36.4 mg, 46.5 L, 0.200 mmol, 1.00 equiv.) and acetone cyanohydrin (17.0 mg, 19.5 L, 0.200 mmol, 1.00 equiv.) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (110 C.). The reaction mixture was then stirred at 110 C. for 12 hours. After cooling to 23 C., the resulting mixture was filtered through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue were purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1:20 (v/v) to afford 35.5 mg (85%) of the title compound as colorless oil.
(253) Rf=0.25 (EtOAc/hexanes 1:20 (v/v)).
(254) NMR Spectroscopy:
(255) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.04 (d, J=20.0 Hz, 1H), 5.97 (d, J=20.0 Hz, 1H), 1.16-1.04 (m, 21H).
(256) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 155.3, 117.8, 114.0, 134.8, 18.5, 10.6.
(257) HRMS-FIA (m/z) calc'd for C.sub.12H.sub.23NSi [M+Na].sup.+, 232.1492, found: 232.1492.
TpRh(COD)
(258) ##STR00069##
(259) According to a literature procedure.sup.15, under argon atmosphere, a 100-mL flask was charged with bis(1,5-cyclooctadiene)rhodium(I) chloride dimer (1.0 g, 2.0 mmol, 1.0 equiv) and KTp (2.0 g, 4.0 mmol, 2.0 equiv), to which DMF (15 mL, c=0.13 M) was added. After the reaction mixture was stirred at 23 C. for 12 h, 30 mL of water was added to the mixture, the resulting suspension was stirred for further 10 min. Then the reaction mixture was filtered, and the filter cake was purified by flash column chromatography on neutral alumina, eluting with methylene dichloride. The yellow band was collected, and the volatiles was evaporated to give 1.3 g (76%) of TpRh(COD) as yellow powder.
(260) NMR Spectroscopy:
(261) .sup.1H NMR (500 MHz, CDCl.sub.3, 23 C., ): 7.77 (br. s, 3H), 7.59 (br. s, 3H), 6.21 (br. s, 3H), 3.87 (br. s, 4H), 2.60-2.58 (m, 4H), 1.93-1.88 (m, 4H), proton of BH is missing.
(262) .sup.13C NMR (125 MHz, CDCl.sub.3, 23 C., ): 139.5, 134.9, 104.9, 73.5, 73.4, 31.3.
(263) .sup.11B NMR (128 MHz, CDCl.sub.3, 23 C., ): 3.57 (d, J=113 Hz).
(264) HRMS-FIA (m/z) calc'd for C.sub.17H.sub.23BN.sub.6Rh [M+H].sup.+, 425.1127, found: 425.1127.
TpRh(dppf)
(265) ##STR00070##
(266) In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (12.7 mg, 0.0300 mmol, 1.00 equiv) and dppf (16.9 mg, 0.0300 mmol, 1.00 equiv).
(267) After adding 1.0 mL of MeCN to the reaction mixture, the vial was sealed with a Teflon cap and moved out of the glovebox to a preheated metal heating block at 110 C. After 1 hour, the resulting mixture was cooled to 23 C. Orange crystals precipitated from the solution within 1 hour. The vial was then placed in a 4 C. fridge for 12 hours. After warming the solution to 23 C., 18.8 mg (72%) of crystals were obtained by careful filtration. The quality of the crystals was suitable for X-ray crystallographic analysis. The compound has a limited lifetime in solution. In solid state, TpRh(dppf) can be oxidized by air.
(268) NMR Spectroscopy:
(269) .sup.1H NMR (500 MHz, CD.sub.2Cl.sub.2, 23 C., ): 7.77-7.58 (br. m, 10H), 7.23-6.93 (br. m, 16H), 6.24 (br. s, 1H), 5.74 (br. s, 1H), 5.42 (br. s, 1H), 4.13-3.89 (br. m, 9H).
(270) .sup.13C NMR (125 MHz, CD.sub.2Cl.sub.2, 23 C., ): 141.3, (d, J=153.5 Hz), 136.5-136.0 (br, m), 134.8 (br, s), 134.1, 133.3-132.4 (br, d), 128.5, 126.7, 103.2, 78.8-78.5 (br, m), 75.1-73.9 (br, m), 71.4.
(271) .sup.31P NMR (202 MHz, CD.sub.2Cl.sub.2, 23 C., ): 46.5 (d, J=183 Hz), 44.7 (d, J=183 Hz).
(272) .sup.11B NMR (128 MHz, CD.sub.2Cl.sub.2, 23 C., ): 1.28 (br. s).
(273) HRMS-FIA (m/z) calc'd for C.sub.43H.sub.38BFeN.sub.6P.sub.2Rh [M+H].sup.+, 871.1214, found: 871.1204.