Method for preparing chiral alkyl compounds by asymmetric hydrogenation of olefins catalyzed by iron complex

Abstract

Provided in the present invention is a method for preparing chiral alkyl compounds by the asymmetric hydrogenation reaction of iron complex catalysts catalysing olefins: using the disubstituted olefin shown in formula I as a raw material, atmospheric hydrogen as a hydrogen source, FeX2-8-OIQ complex as a catalyst, and a silane compound and acetonitrile as cocatalysts, and reacting for 12-24 hours under the action of a reducing agent to prepare the chiral alkyl compound shown in formula II. The method of the present invention has mild reaction conditions, simple operation, and high atom economy. In addition, the reaction does not require the addition of any other toxic transition metal (such as ruthenium, rhodium, and palladium), and has great practical application value in the synthesis of drugs and materials. The conversion rate of the reaction is also good, generally reaching >99%, and the enantioselectivity is also high, generally 70-99%. ##STR00001## ##STR00002##

Claims

1. A method for preparing chiral alkyl compounds by asymmetric hydrogenation of olefins catalyzed by iron complex catalyst, wherein the method is as follows: reacting a disubstituted olefin shown in Formula I as a raw material, atmospheric hydrogen as hydrogen source, FeX2-8-OIQ complex as catalyst, hydrosilane and acetonitrile as co catalysts, for 12-24 hours under the activation of a reducing agent, to prepare a chiral alkyl compound shown in Formula II; wherein; ##STR00040## in Formula II, * represents a chiral carbon atom; in Formula I or Formula II, R.sup.1 is C.sub.2C.sub.8 alkyl, naphthyl, a group shown in Formula III, or a N and O containing heterocyclic aryl group of C.sub.4C.sub.10; in R.sup.1, the H on C.sub.2C.sub.8 alkyl is not substituted or substituted by at least one substituent A, selected from the group consisting of and the substituent A is selected from the group consisting of phenyl, naphthyl, heterocyclic aryl or substituted phenyl; heterocyclic aryl is indolyl, pyridinyl, pyrrolyl, thiophenyl and furanyl; substituted phenyl is the phenyl group in which H on phenyl is replaced by at least one substituent B, and the substituent B is selected from the group consisting of C.sub.1C.sub.3 alkyl, C.sub.1C.sub.3 alkoxy, halogen and C.sub.1C.sub.3 alkylthio; in R.sup.1, the N and O containing heterocyclic aryl group of C.sub.4C.sub.10 is selected from the group consisting of pyridinyl, pyrrolyl, indolyl, benzodioxazolyl, benzoxazolyl and furanyl; in R.sup.1, the H on naphthyl and the N and O containing heterocyclic aryl group of C.sub.4C.sub.10 are not substituted or substituted by at least one substituent C, and the substituent C is C.sub.1C.sub.3 alkyl or C.sub.1C.sub.3 alkoxy; ##STR00041## in R.sup.1, among the groups shown in Formula III, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 are selected from the group consisting of H, halogen, C.sub.1C.sub.2 alkyl, C.sub.1C.sub.3 alkoxy, benzyloxy, C.sub.1C.sub.3 alkylthio, tert butyl dimethyl siloxy, trifluoromethyl, dimethylamino, pinacol borate, d-borneoxy, citronellol oxy, menthol oxy or geraniol oxy, and when R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 are all H, Formula III is phenyl; and halogen is F or Cl; in Formula I or Formula II, R.sup.2 is C.sub.1C.sub.8 alkyl, C.sub.2C.sub.8 alkenyl, phenyl or benzyl; the H on C.sub.1C.sub.8 alkyl and C.sub.2C.sub.8 alkenyl are not substituted or substituted by at least one substituent D selected from the group consisting of phenyl, substituted phenyl, C.sub.1C.sub.3 amino or 1,3-dioxolacyl; or in Formula I or Formula II, R.sup.1 and R.sup.2 are connected into a ring to form C.sub.9C.sub.12 benzocycloalkyl; H on C.sub.9C.sub.12 benzocycloalkyl is not substituted or substituted by at least one substituent E, and the substituent E is selected from the group consisting of C.sub.1C.sub.3 alkyl, C.sub.1C.sub.3 alkoxy or halogen; R.sup.1 and R.sup.2 are different substituents; wherein the catalyst FeX2-OIQ complex is an optically pure compound shown in Formula IV or its enantiomer or racemate; ##STR00042## wherein in Formula IV, R.sup.9 is C1-C12 alkyl which is unsubstituted or substituted by one or two C1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by one to three substituents A, or aryl A which is unsubstituted or substituted by 1-4 substituents B; the aryl A is selected from the group consisting of benzyl, phenyl and naphthyl; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl; R.sup.10 is selected from the group consisting of H, C1-C12 alkyl which is unsubstituted or substituted by one or two C1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A, or aryl B which is unsubstituted or substituted by 1-3 substituents A; the aryl B is phenyl or naphthyl; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl; R.sup.11, R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are independently selected from the group consisting of H, C1-C12 alkyl, C1-C4fluoroalkoxy, F, CI, nitro and C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H and C1-C12 alkyl A which is unsubstituted or substituted by one or two C1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A, or aryl A which is unsubstituted or substituted by 1-3 substituents B; the aryl A is selected from the group consisting of benzyl, phenyl and naphthyl; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl; R.sup.18 is selected from the group consisting of C1C12 alkyl group that is not substituted or substituted by 1-2 C1C4 alkoxy, C5-C12 cycloalkyl which is not substituted or substituted by 1-3 substituents A, or aryl A which is not substituted or substituted by 1-3 substituents B; the aryl A is selected from the group consisting of benzyl, phenyl and naphthyl; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl; in Formula IV,* represents a chiral carbon atom; X is selected from the group consisting of F, Cl, Br, I, OAc and CF3SO3--; and wherein the reducing agent is selected from the groups consisting of sodium triethylborohydride, sodium tri-sec-butyl-borohydride, lithium triethylborohydride, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium tert-pentoxide, sodium ethoxide, sodium methoxide and potassium methoxide.

2. The method according to claim 1, wherein R.sup.1 is C.sub.2C.sub.8 alkyl, naphthyl, 6-methoxynaphthalyl, pyridinyl, 2-methoxypyridyl, indolyl, N-methylindolyl, benzodioxazolyl and the group shown in Formula III; in R.sup.1, when R.sup.1 is C.sub.2C.sub.8 alkyl, H on C.sub.2C.sub.8 alkyl is replaced by a substituent A, R.sup.1 is selected from the group consisting of expressed as R.sup.A(CH.sub.2).sub.n, wherein n is an integer of 2 to 8, R.sup.A is a substituent A on the carbon chain, and R.sup.A is phenyl, naphthyl or p-methoxyphenyl; the group shown in Formula III is phenyl or substituted phenyl with 1-2 substituents, and the substituent on the substituted phenyl is selected from the group consisting of halogen, C.sub.1C.sub.2 alkyl, C.sub.1C.sub.3 alkoxy, benzyloxy, C.sub.1C.sub.3 alkylthio, tert-butyl dimethyl siloxy, trifluoromethyl, dimethylamino, pinacol borate, d-borneol, citronellol-oxyl, menthol-oxyl and geraniol-oxyl; R.sup.2 is selected from the group consisting of C.sub.2C.sub.6 alkyl, C.sub.2C.sub.6 alkenyl, phenyl or benzyl; H on the C.sub.2C.sub.6 alkyl is not substituted or substituted by substituent D, R.sup.2 is C.sub.2C.sub.6 alkyl, and when H on the alkyl is substituted by substituent D, R.sup.2 is expressed as R.sup.D(CH.sub.2).sub.m, m is an integer of 2 to 6, and the substituent D is phenyl, C.sub.1C.sub.3 amino, 4-methoxyphenyl and 1,3-dioxolacyl.

3. The method according to claim 1, wherein the catalyst FeX.sub.2-8-OIQ complex is a compound shown in Formula IV, wherein R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16 and R.sup.17 are H; R.sup.10 is C.sub.1C.sub.4 alkyl or diphenylmethylene; R.sup.9 is C.sub.1C.sub.4 alkyl, benzyl, phenyl or 2,6-diisopropylphenyl; R.sup.18 is selected from the group consisting of C.sub.1C.sub.4 alkyl, benzyl or phenyl; X is Cl or Br.

4. The method according to claim 1, wherein the FeX.sub.2-8-OIQ complex is shown in Formula IV-1 or Formula IV-2, ##STR00043##

5. The method according to claim 1, wherein the silane compound is benzene silane or n-octadecyl silane.

6. The method according to claim 1, wherein an organic solvent is added to the method, and the organic solvent is selected from the group consisting of benzene, carbon tetrachloride, toluene, tetrahydrofuran, ether, dichloromethane, acetonitrile, dioxane, petroleum ether, cyclohexane, n-hexane, ethyl acetate, chloroform, and dimethylformamide.

7. The method according to claim 1, wherein the mole ratio of the disubstituted olefin shown in Formula I, FeX.sub.2-8-OIQ complex, silane compound, acetonitrile and reducing agent is 1:0.00001-0.1:0.02-0.2:0.1-0.3:0.06-0.3.

8. The method according to claim 1, wherein the reaction temperature is 0 C.room temperature.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1: X-ray diffraction spectrogram of the catalyst of formula IV-2.

(2) FIG. 2: X-ray diffraction spectrogram of the asymmetric hydrogenation product of formula II-3.

DETAILED DESCRIPTION

(3) The technical scheme of the invention is further described in detail by specific embodiments, but the protection scope of the invention is not limited to this.

(4) The catalyst used in the embodiment is shown below, and the compound shown in Formula IV-1 is referred to as FeCl.sub.2-8-OIQ for short.

(5) The preferred amount of metal complex is 0.001-10 mol %, more preferably 0.1-5 mol %.

(6) The X-ray diffraction spectrogram of Formula IV-2 is shown in FIG. 1, CCDC Number: 2011869.

(7) The catalyst synthesis route is as follows:

(8) ##STR00015##

(9) The synthesis steps of the catalyst are as follows. The amine compounds shown in Formula (3) are commercially available, and the 2-acyl-8-bromoquinoline compounds shown in Formula (2) are prepared in accordance with the literature (K. ukowska, E. Pump, A. E. Pazio, K. Woniak, L. Cavallo, C. Slugovc Beilstein J. Org. Chem. 2015, 11, 1458.) o Oxazoline compounds shown in Formula (5) are synthesized according to the literature (J. Chen, T. Xi, Z. Lu Org. Chem. Front., 2018, 5, 247.)

(10) Preparation of 8-bromo-2-acetylquinoline (2)

(11) Under the protection of nitrogen, the 8-bromo-formylquinoline (6.9451 g, 29.3 mmol, 1.0 equiv) and ethyl ether (147 ml) were added in three necked flask (250 mL). Then methyl magnesium bromide (3 M in hex 12.7 mL 1.3 equiv) was dropped at 0 C. After dropping, the reaction stirred in room temperature for 12 hours. The mixture was quenched with saturated aqueous ammonium chloride solution (10 mL). The aqueous layer was separated and extracted with ether (3 times). The organic layers were combined, dried over anhydrous Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The crude material was concentrated and diluted with dichloromethane, 22.31 g of PDC (pyridinium dichromate 58.8 mmol, 2.0 equiv) and silica gel (23.10 g) were added in reaction and stirring overnight at room temperature. After the reaction conducted, the solid was filtered and wash with dichloromethane, concentrated in vacuo to obtain a yellow solid, The crude material was subsequently purified via column chromatography on silica gel to afford the 8-bromo-2-acetylquinoline with white solid (17.4 mmol, 4.3615 g, 59% yield).

(12) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.07-7.99 (m, 2H), 7.93 (d, J=8.0 Hz, 1H), 7.65-7.58 (m, 1H), 7.56 (d, J=8.8 Hz, 1H), 2.96 (s, 3H); the data is consistent with the literature [S. Nagy, L. N. Winslow, S. Mihan; L. Lukesova, E. Nifant'ev, P. V. Ivchenko, V. Bagrov, US Patent 2012/0016092 2012.]

(13) Preparation of 8-bromo-2-iminoquinoline (4)-S

(14) 2,6-Diisopropylaniline (4.2516 g, 24 mmol, 1.2 equiv) 8-Bromo-2-acetylquinoline (5.0 g, 20 mmol, 1.0 equiv) were added in toluene (50 mL), then P-toluenesulfonic acid monohydrate (0.0761 g, 0.40 mmol, 2 mol %) was added, the mixtures was refluxed for 24 h and the water was separated by water separator, then the crude product was recrystallized with ethanol to afford the (4)-S with 7.3078 g (17.9 mmol, 90% yield) IR (neat): 2959, 2924, 1696, 1643, 1493, 1462, 1362 cm.sup.31 1; 1H NMR: (400.0 MHz, CDCl3) 8.60 (d, J=8.8 Hz, 1H), 8.24 (d, J=8.4 Hz, 1H), 8.10 (d, J=7.2 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.46 (dd, J=8.0,7.6 Hz, 1H), 7.22-7.17 (m, 2H), 7.15-7.10 (m, 1H), 2.80-2.72 (m, 2H), 2.43 (s, 3H), 1.17 (d, J=3.2 Hz, 6H), 1.15 (d, J=3.2 Hz, 6H); 13C NMR: (100.6 MHz, CDCl3) 167.3, 156.5, 146.5, 144.3, 136.6, 135.5, 133.1, 130.0, 127.8, 127.4, 125.9, 123.7, 123.0, 119.4, 28.3, 23.2, 22.8, 16.9; HRMS (ESI) calculated for [C23H26BrN2]+ (M+H+), requires m/z 409.1279, found m/z 409.1290.

(15) Synthesis of Ligand L

(16) Under nitrogen, (4)-S (1.0213 g, 2.52 mmol, 1 equiv) and (S)-isopropyl oxazoline (0.3821 g, 3.375 mmol, 1.35 equiv) were added in dioxane (15 mL), Pd(OAc).sub.2 (0.0281 g, 0.0125 mmol, 5 mol %), dppe(0.0558 g, 0.14 mmol, 5.6 mol %), tBuOLi (0.4005 g, 5 mmol, 2 equiv) were added into the system, respectively. The reaction was degassed three times and stirred in 110 C. for 41 h, The crude material was subsequently purified via column chromatography on silica gel to afford the ligand L with 0.8456 g (1.9 mmol, 76% yield).

(17) Synthesis of Iron Catalyst:

(18) A 50 mL Schleck flask was charged with 0.95 eq. of FeCl.sub.2, THF (0.1 M) and a solution of 1.0 eq. of (S)-La in THF under atmosphere of nitrogen. The mixture was stirred at room temperature for 17 h. The solvent was removed in vacuo. The resulting mixture was washed with ether and filtered under air. The cake was washed with ether and dried in vacuo to afford IV-1 and IV-2.

(19) ##STR00016##

Example 1

the FeX.SUB.2.-8-OI-Catalyzed Asymmetric Hydrogenation of 1,1-Disubstituted Alkenes

(20) General procedure for asymmetric hydrogenation of 1,1-disubstituted alkenes: A 25 mL flame-dried Schleck flask was cooled at room temperature under nitrogen, charged with LeFeCl.sub.2 (0.025 mmol), alkene (0.50 mmol), hydrosilane (0.10 mmol), the system was purged one time, The acetonitrile (0.10 mmol) and dry toluene (1 mL) were added successively, then NaBHEt3 (1 M in THF) (75 L, 0.075 mmol) was injected slowly, the reaction was stirred 5 min, a balloon with hydrogen was added and the system was purged three times. The mixture was stirred for 12 hours in room temp. The reaction was quenched by PE. The mixture was filtered through a pad of silica gel and washed with PE (50 mL). The filtrate was concentrated without further purification to afford the corresponding product.

(21) II-1: (R)-1-(sec-butyl)-4-methoxybenzene

(22) ##STR00017##

(23) A colorless oil, >99% conversion. Optical Rotation: [].sub.20.sup.D=23.2 (c 1.11, CHCl.sub.3), 99% ee. .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.10 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 3.79 (s, 3H), 2.59-2.50 (m, 1H), 1.61-1.49 (m, 2H), 1.21 (d, J=7.2 Hz, 3H), 0.81 (t, J=7.6 Hz, 3H).

(24) II-2: (R)-1-(benzyloxy)-4-(sec-butyl)benzene

(25) ##STR00018##

(26) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=8.6 (c 1.35, CHCl.sub.3). 98% ee. IR (neat): 2961, 2925, 1510, 1488 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.45-7.30 (m, 5H), 7.10 (d, J=8.8 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 5.04 (s, 2H), 2.59-2.51 (m, 1H), 1.60-1.52 (m, 2H), 1.21 (d, J=6.8 Hz, 3H), 0.82 (t, J=7.2 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 156.9, 140.1, 137.3, 128.5, 127.9, 127.8, 127.5, 114.5, 70.0, 40.8, 31.3, 22.0, 12.2; HRMS (EI) calculated for [C.sub.17H.sub.20O].sup.+ requires m/z 240.1514, found m/z 240.1516.

(27) II-3: (R)-2-(4-(sec-butyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

(28) ##STR00019##

(29) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=2.1 (c 1.18, CHCl.sub.3). 94.4% ee, IR (neat): 2960, 2855, 1611, 1401, 1362, 1145 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.75 (d, J=8.0 Hz, 2H), 7.19 (d, J=8.0 Hz, 2H), 2.65-2.55 (m, 1H), 1.65-1.55 (m, 2H), 1.33 (s, 12H), 1.23 (d, J=6.8 Hz, 3H), 0.81 (t, J=7.6 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 151.1, 134.8, 126.5, 83.6, 41.9, 31.0, 24.8, 21.7, 12.2; HRMS (EI) calculated for [C.sub.16H.sub.25O.sub.2B].sup.+ requires m/z 260.1948, found m/z 260.1949. The x-ray diffraction was added in FIG. 2. CCDC number: 2055703.

(30) II-4: (R)-(4-(sec-butyl)phenyl)(methyl)sulfane

(31) ##STR00020##

(32) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=18.1 (c 1.03, CHCl.sub.3). 95.1% ee, IR (neat): 2960, 2923, 1561, 1494, 1458, 1144 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.21 (d, J=8.0 Hz, 2H), 8.3 (d, J=8.0 Hz, 2H), 2.60-2.51 (m, 1H), 2.47 (s, 3H), 1.61-1.54 (m, 2H), 1.21 (d, J=6.8 Hz, 3H), 0.81 (t, J=7.6 Hz, 3H); .sup.13C NMR: (100.6 MHz, CDCl.sub.3) 144.9, 135.0, 127.6, 127.1, 41.2, 31.1, 21.8, 16.3, 12.2; HRMS (EI) calculated for [C.sub.11H.sub.16S].sup.+ requires m/z 180.0973, found m/z 180.0974.

(33) II-5: (R)-5-(sec-butyl)benzo[d][1,3]dioxole

(34) ##STR00021##

(35) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=12.8 (c 0.30, CHCl.sub.3). 98.6% ee, .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.11-7.06 (m, 5H), 2.60-2.51 (m, 1H), 2.32 (s, 3H), 1.61-1.52 (m, 2H), 1.22 (d, J=6.8 Hz, 3H), 0.82 (t, J=7.2 Hz, 3H). IR (neat): 2961, 2927, 1487, 1440, 1249 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 6.73 (d, J=8.0 Hz, 1H), 6.68 (s, 1H), 6.62 (d, J=8.0 Hz, 1H), 5.92 (s, 2H), 2.57-2.47 (m, 1H), 1.60-1.48 (m, 2H), 1.19 (d, J=6.8 Hz, 3H), 0.81 (t, J=7.2 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 147.5, 145.4, 141.7, 119.9, 107.9, 107.2, 100.7, 41.5, 31.3, 22.1, 12.2; HRMS (EI) calculated for [C.sub.11 H.sub.14O.sub.2].sup.+ requires m/z 178.0994, found m/z 178.0992.

(36) II-6: (R)-1-(sec-butyl)-4-fluorobenzene

(37) ##STR00022##

(38) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=12.7 (c 1.25, CHCl.sub.3). 92.1% ee. .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.16-7.09 (m, 2H), 7.00-6.92 (m, 2H), 2.63-2.53 (m, 1H), 1.61-1.51 (m, 2H), 1.21 (d, J=6.8 Hz, 3H), 0.80 (t, J=7.2 Hz, 3H); .sup.13C NMR: (100.6 MHz, CDCl.sub.3) 161.1 (d, J=241.3 Hz), 143.2 (d, J=2.9 Hz), 128.3 (d, J=7.3 Hz), 114.9(d, J=20.4 Hz), 41.0, 31.3, 22.0, 12.1; .sup.19F NMR: (376 MHz, CDCl.sub.3) -118.1.

(39) II-7: (R)-1-(sec-butyl)-4-chlorobenzene

(40) ##STR00023##

(41) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=3.2 (c 1.37, CHCl.sub.3). 94.3% ee, IR (neat): 2958, 2925, 2855, 1493, 1461, 1378 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.25 (d, J=8.4 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 2.61-2.53 (m, 1H), 1.62-1.51 (m, 2H), 1.21 (d, J=6.8 Hz, 3H), 0.80 (t, J=7.2 Hz, 3H); .sup.13C NMR: (100.6 MHz, CDCl.sub.3) 146.1, 131.3, 128.4, 128.3, 41.1, 31.1, 21.8, 12.1; HRMS (EI) calculated for [C.sub.10H.sub.13Cl].sup.+ requires m/z 168.0706, found m/z 168.0706.

(42) II-8: (R)-1-(sec-butyl)-3-methoxybenzene

(43) ##STR00024##

(44) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=21.4 (c 0.97, CHCl.sub.3). 95.4% ee, IR (neat): 2960, 2922, 1604, 1487, 1458, 1261 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.21 (t, J=7.8 Hz, 1H), 6.79-6.72 (m, 3H), 3.80 (s, 3H), 2.61-2.52 (m, 1H), 1.64-1.00 (m, 2H), 1.23 (d, J=6.8 Hz, 3H), 0.83 (t, J=7.2 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 159.6, 149.5, 129.1, 119.5, 113.0, 110.7, 55.1, 41.7, 31.1, 21.8, 12.2; HRMS (EI) calculated for [C.sub.11H.sub.16O].sup.+ requires m/z 164.1201, found m/z 164.1203.

(45) II-9: (R)-1-(sec-butyl)-2-methoxybenzene

(46) ##STR00025##

(47) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=1.4 (c 0.51, CHCl.sub.3). 77.4% ee, IR (neat): 2921, 2853, 1511, 1464, 1380, 1246 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.19-7.12 (m, 2H), 6.95-6.82 (m, 2H), 3.81 (s, 3H), 3.16-3.04 (m, 1H), 1.70-1.54 (m, 2H), 1.19 (d, J=6.8 Hz, 3H), 0.84 (t, J=6.8 Hz, 3H); .sup.13C NMR: (100.6 MHz, CDCl.sub.3) 157.1, 135.9, 126.7, 126.4, 120.5, 110.4, 55.3, 33.4, 29.8, 20.4, 12.1; HRMS (EI) calculated for [C.sub.11H.sub.16O].sup.+ requires m/z 164.1201, found m/z 164.1202.

(48) II-10: (R)-5-(sec-butyl)-1-methyl-1H-indole

(49) ##STR00026##

(50) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=16.0 (c 1.11, CHCl.sub.3). 97.9% ee, IR (neat): 2958, 2919, 1513, 1490 1450, 1352 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.42 (s, 1H), 7.28-7.23 (m, 1H), 7.07 (d, J=7.6 Hz, 1H), 7.01 (d, J=2.8 Hz, 1H), 6.42 (d, J=2.8 Hz, 1H), 3.77 (s, 3H), 2.74-2.63 (m, 1H), 1.71-1.59 (m, 2H), 1.29 (d, J=6.8 Hz, 3H), 0.83 (t, J=7.2 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 138.6, 135.4, 128.7, 128.5, 121.1, 118.6, 108.8, 100.5, 41.7, 32.7, 31.6, 22.6, 12.4; HRMS (EI) calculated for [C.sub.13H.sub.17N].sup.+ requires m/z 187.1361, found m/z 187.1362.

(51) II-11: (R)-1-(hexan-2-yl)-4-methoxybenzene

(52) ##STR00027##

(53) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=27.4 (c 0.89, CHCl.sub.3). 93.9% ee, IR (neat): 2957, 2927, 1611, 1512, 1461, 1247 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.10 (d, J=8.8 Hz, 2H), 6.83 (d, J=8.8 Hz, 2H), 3.79 (s, 3H), 2.67-2.57 (s, 1H), 1.56-1.48 (m, 2H), 1.34-1.07 (m, 7H), 0.85 (t, J=6.8 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 157.6, 140.1, 127.8, 113.6, 55.2, 39.0, 38.3, 29.9, 22.8, 22.5, 14.0; HRMS (EI) calculated for [C.sub.13H.sub.20O].sup.+ requires m/z 192.1514, found m/z 192.1514.

(54) II-12: (R)-1-(heptan-2-yl)-4-methoxybenzene

(55) ##STR00028##

(56) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=26.7 (c 0.75, CHCl.sub.3). 94.8% ee, IR (neat): 2923, 2854, 1612, 1512, 1461, 1375 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.09 (d, J=8.8 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 3.79 (s, 3H), 2.67-2.57 (m, 1H), 1.55-1.47 (m, 2H), 1.30-1.10 (m, 9H), 0.85 (t, J=6.4 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 157.6, 140.1, 127.7, 113.6, 55.1, 39.0, 38.6, 31.9, 27.4, 22.6, 22.5, 14.1; HRMS (EI) calculated for [C.sub.14H.sub.22O].sup.+ requires m/z 206.1671, found m/z 206.1672.

(57) II-13: (R)-1-methoxy-4-(octan-2-yl)benzene

(58) ##STR00029##

(59) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=23.4 (c 1.20, CHCl.sub.3). 90.8% ee, IR (neat): 2955, 2854, 1612 1512, 1461, 1375 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.09 (d, J=8.8 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 3.79 (s, 3H), 2.67-2.57 (m, 1H), 1.56-1.48 (m, 2H), 1.30-1.10 (m, 11H), 0.85 (t, J=6.4 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 157.6, 140.1, 127.7, 113.6, 55.1, 39.1, 38.6, 31.8, 29.4, 27.7, 22.6, 22.5, 14.1; HRMS (EI) calculated for [C.sub.15H.sub.24O].sup.+ requires m/z 220.1827, found m/z 220.1826.

(60) II-14: (R)-N,N-dimethyl-4-(p-tolyl)pentan-1-amine

(61) ##STR00030##

(62) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=17.4 (c 0.92, CHCl.sub.3). 96.6% ee, IR (neat): 2941, 2858, 2763, 1651, 1515, 1374 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.12-7.04 (m, 4H), 2.70-2.59 (m, 1H), 2.31 (s, 3H), 2.25-2.14 (m, 8H), 1.61-1.52 (m, 2H), 1.47-1.28 (m, 2H), 1.23 (d, J=6.8 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 144.4, 135.2, 128.9, 126.8, 59.8, 45.4, 39.5, 36.1, 25.8, 22.4, 20.9; HRMS (EI) calculated for [C.sub.14H.sub.23N].sup.+ requires m/z 205.1830, found m/z 205.1832.

(63) II-15: (R)-propane-1,2-diyldibenzene

(64) ##STR00031##

(65) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=33.9 (c 1.09, CHCl.sub.3). 84.3% ee, .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.35-7.01 (m, 10H), 3.07-2.88 (m, 2H), 2.83-2.69 (m, 1H), 1.24 (d, J=6.8 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 147.0, 140.8, 129.1, 128.3, 128.1, 127.0, 126.0, 125.8, 45.0, 41.8, 21.1.

(66) II-16: (1R,3R)-3-(4-((R)-sec-butyl)phenoxy)-1,7,7-trimethylbicyclo[2.2.1]heptane

(67) ##STR00032##

(68) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=88.3 (c 0.79, CHCl.sub.3). 96% ee, IR (neat): 2955, 2875, 1610, 1510, 1455, 1245 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.06 (d, J=8.8 Hz, 2H), 6.76 (d, J=8.8 Hz, 2H), 4.32-4.25 (m, 1H), 2.58-2.47 (m, 1H), 2.40-2.30 (m, 1H), 2.29-2.18 (m, 1H), 1.81-1.69 (m, 2H), 1.61-1.50 (m, 2H), 1.23-1.37 (m, 2H), 1.20 (d, J=7.2 Hz, 3H) 1.13 (dd, J=13.2, 3.2 Hz, 1H), 0.97-0.88 (m, 9H), 0.81 (t, J=7.2 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 157.2, 139.2, 127.7, 115.1, 82.7, 49.5, 47.5, 45.2, 40.8, 36.9, 31.3, 27.9, 26.8, 22.0, 19.7, 19.0, 13.8, 12.3. HRMS (EI) calculated for [C.sub.20H.sub.30O].sup.+ requires m/z 286.2297, found m/z 286.2297.

(69) II-17: (R,E)-1-(sec-butyl)-4-((3,7-dimethylocta-2,6-dien-1-yl)oxy)benzene

(70) ##STR00033##

(71) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=13.1 (c 0.78, CHCl.sub.3). 97.2% ee, IR (neat): 2963, 2922, 1671, 1611, 1511, 1455 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.08 (d, J=8.8 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 5.50 (t, J=6.8 Hz, 1H), 5.10 (t, J=5.2 Hz, 1H), 4.51 (d, J=6.8 Hz, 2H), 2.59-2.48 (m, 1H), 2.18-2.04 (m, 4H), 1.73(s, 3H),1.68 (s, 3H), 1.58 (s, 3H), 1.57-1.51 (m, 2H), 1.21 (d, J=6.8 Hz, 3H), 0.81 (t, J=7.6 Hz, 3H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 157.0, 140.8, 139.6, 131.7, 127.8, 123.8, 119.8, 114.4, 64.8, 40.8, 39.5, 31.3, 26.3, 25.6, 22.0, 17.6, 16.6, 12.2. HRMS (EI) calculated for [C.sub.20H.sub.30O].sup.+ requires m/z 286.2297, found m/z 286.2298.

(72) II-18: (R)-2-(3-(3-methoxy-4-methylphenyl)butyl)-1,3-dioxolane

(73) ##STR00034##

(74) A colorless oil, >99% conversion. Optical Rotation: [].sup..sub.D=11.4 (c 1.98, CHCl.sub.3). 97.2% ee, IR (neat): 2954, 2926, 1611, 1582, 1462, 1256 cm.sup.1; .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.03 (d, J=7.6 Hz, 1H), 6.71-6.63 (m, 2H), 4.81 (t, J=4.8 Hz, 1H), 4.01-3.79 (m, 7H), 2.71-2.59 (m, 1H), 2.17 (s, 3H), 1.73-1.49 (m, 4H), 1.25 (d, J=7.2 Hz, 3H); 13C NMR: (100.0 MHz, CDCl3) 157.6, 146.1, 130.4, 124.0, 118.6, 108.8, 104.6, 64.8, 55.2, 39.9, 32.4, 32.1, 22.4, 15.8; HRMS (EI) calculated for [C.sub.15H.sub.22O.sub.3]+ requires m/z 250.1569, found m/z 250.1569.

(75) II-19: (R)-5-methyl-6,7,8,9-tetrahydro-5H-benzo[7]annulene

(76) ##STR00035##

(77) A colorless oil, >99% conversion. Optical Rotation: [].sup.20.sub.D=+10.6 (c 0.50, CHCl.sub.3). 90.5% ee, .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 7.22-7.04 (m, 4H), 3.10-2.99 (m, 1H), 2.93-2.83 (m, 1H), 2.83-2.74 (m, 1H), 1.98-1.86 (m, 1H), 1.86-1.68 (m, 3H), 1.51-1.30 (m, 5H); .sup.13C NMR: (100.0 MHz, CDCl.sub.3) 146.5, 142.8, 129.2, 126.0, 125.6, 125.2, 37.7, 36.1, 36.0, 30.1, 27.8, 20.4.

(78) II-20: (R) -1-(3,4-dimethylpentyl)-4-methoxybenzene

(79) ##STR00036##

(80) A colorless oil, 42% conversion. 54% ee. .sup.1 H NMR: (400.0 MHz, CDCl.sub.3) 7.10 (d, J=8.0 Hz, 2H), 6.82 (d, J=8.0 Hz, 2H), 3.79 (s, 3H), 2.66-2.55 (m, 1H), 2.53-2.41 (m, 1H), 1.69-1.56 (m, 2H), 1.44-1.25 (m, 2H), 0.93-0.77 (m, 9H).

Example 2

Selective Hydrogenation of 1,1-Disubstituted Olefins Using the Catalyst FeCl.SUB.2.-8-OIQ (tBuoxazole Ring) with Large Steric Hindrance

(81) ##STR00037##

(82) A 25 mL flame-dried Schleck flask was cooled at room temperature under nitrogen, charged with LeFeCl.sub.2 (0.025 mmol), alkene (0.50 mmol), hydrosilane (0.10 mmol), the system was purged one time, The acetonitrile (0.10 mmol) and dry toluene (1 mL) were added successively, then NaBHEt3 (1 M in THF) (75 L, 0.075 mmol) was injected slowly, the reaction was stirred 5 min, a balloon with hydrogen was added and the system was purged three times. The mixture was stirred for 12 hours in room temp. The reaction was quenched by PE. The mixture was filtered through a pad of silica gel and washed with PE (50 mL). The filtrate was concentrated without further purification to afford the corresponding product with >99% conversion. Optical Rotation: [].sup.20.sub.D=32.5 (c 1.75, CHCl.sub.3). 93% ee. The (R)-xanthorrhizol could be synthesized according to the literature.

Example 3

Synthesis of Drug Intermediates

(83) ##STR00038##

(84) To (R)-2-(3-(p-tolyl)butyl)-1,3-dioxolane (II-18) (0.0404 g, 1 equiv) was added a solution of AcOH (6 ml) and H.sub.2O (2 ml). The reaction mixture was stirred at 60 C. for 5 h and then was cooled down to room temperature. Adding the sodium hydroxide solution to adjust pH to 7, then exacted with ethyl acetate (310 mL), the solvent was removed in vacuo, providing the crude residue. The crude material was purified by column chromatography (PE/EA (30/1)) to give the intermediate of (R)-curcumene (0.0286 g, 88% yield) as a colorless oil. Optical Rotation: [].sup.20.sub.D=33.9 (c 0.91, CHCl.sub.3). 96% ee. Optical Rotation: [].sup.20.sub.D=33.9 (c 0.91, CHCl.sub.3). 96% ee, .sup.1H NMR: (400.0 MHz, CDCl.sub.3) 9.68 (t, J=1.6 Hz, 1H), 7.14-7.03 (m, 4H), 2.75-2.63 (m, 1H), 2.39-2.24 (m, 2H), 1.99-1.79 (m, 2H), 1.26 (d, J=7.2 Hz, 3H); .sup.13C NMR: (100.6 MHz, CDCl.sub.3) 202.4, 142.9, 135.7, 129.1, 126.8, 42.1, 38.8, 30.3, 22.3, 20.9. (: Song, S.; Zhu, S. -F.; Yang, S.; Li, S.; Zhou, Q. -L. Angew. Chem. Int. Ed. 2012, 51, 2708.)

Example 4

Comparative Experiment on Catalytic Performance and Reaction Conditions of Various Catalysts

(85) ##STR00039##

(86) TABLE-US-00001 yield of recovery isom. ee of 2a entry cat. 2a (%).sup.b of 1a (%) (%) (%).sup.c Note 1 OIPFeCl.sub.2 25 51 24 58 LP17107 2 LaFeCl.sub.2 >99 0 0 88 LP15115-B 3 LbFeCl.sub.2 98 0 2 99 LP15114-A 4 LcFeCl.sub.2 98 0 2 97 LP15115-A 5 LdFeCl.sub.2 >99 0 0 99 LP17005 .sup.a The reactions were conducted using alkene (0.5 mmol), H.sub.2 balloon, hydrosilane (20 mol %), CH.sub.3CN (20 mol %), iron cat. (5 mol %), NaBHEt.sub.3 (15 mol %), and toluene (1 mL) at rt for 12 h; .sup.bThe conversions and recoveries were determined by .sup.1H NMR using TMSPh as an internal standard; ee values were determined by GC using chiral column.