METHOD FOR PREPARING ALKENYL AMINOBORANES AND THEIR DERIVATIVES, AND USES THEREOF
20220396591 · 2022-12-15
Inventors
Cpc classification
C07F7/081
CHEMISTRY; METALLURGY
B01J21/066
PERFORMING OPERATIONS; TRANSPORTING
C07J51/00
CHEMISTRY; METALLURGY
International classification
B01J21/06
PERFORMING OPERATIONS; TRANSPORTING
Abstract
Disclosed is a method for preparing alkenyl aminoboranes and their derivatives, and uses thereof. The method for preparing alkenyl aminoboranes includes contacting, preferably in a single synthesis step, a terminal alkyne, an aminoborane and a catalyst chosen from Schwartz's reagent (Cp2ZrHCl), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2) and 9-Borabicyclo(3.3.1)nonane (9-BBN).
Claims
1. Method for the preparation of an alkenylaminoborane of the following formula (I): ##STR00103## wherein R is: a linear or branched alkyl group of 1 to 18 carbon atoms optionally bearing at least one substituent, a linear or branched alkenyl or alkynyl group of 2 to 18 carbon atoms, optionally bearing at least one substituent, a cycloalkyl or cycloalkenyl group of 3 to 18 carbon atoms, optionally bearing at least one substituent, a heterocycloalkyl or heterocycloalkenyl group, optionally bearing at least one substituent, an aryl group of 2 to 12 carbon atoms, where the aryl is chosen from the group of aromatics or heteroaromatics, optionally bearing at least one substituent, an alkyl aryl group, where the aryl is chosen from the group of aromatics or heteroaromatics, optionally bearing at least one substituent, a halogen chosen from F, Cl, Br, and I, a silyl group —SiR.sub.aR.sub.bR.sub.c, —R.sub.aSiR.sub.bR.sub.cR.sub.d, —R.sub.aOSiR.sub.bR.sub.cR.sub.d, a —OR.sub.a, —NHR.sub.a, —NR.sub.aR.sub.b, —SR.sub.a, —CF.sub.3, —NO.sub.2, —R.sub.aOR.sub.b, —R.sub.aNHR.sub.b, —R.sub.aNR.sub.bR.sub.c, —R.sub.aSR.sub.b, group in which R.sub.a, R.sub.b, R.sub.c and R.sub.d, identical or different, represent H, Cl atoms, linear or branched alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl groups, optionally bearing at least one substituent, where said substituents are chosen from: a linear, branched or cyclic alkyl groups of 1 to 18 carbon atoms, the halogens F, Cl, Br and I, OH, R.sub.1 is a group chosen from isopropyl, cyclohexyl, n is an integer from 1 to 3, comprising bringing into contact: a terminal alkyne, of the following formula: ##STR00104## R having the meanings indicated above, of an aminoborane of formula BH.sub.2—N(R.sub.1).sub.2, and a catalyst selected from the group consisting of: Schwartz's reagent (Cp.sub.2ZrHCl), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2), 9-borabicyclo(3.3.1)nonane (9-BBN).
2. Method according to claim 1, wherein the method is carried out at a temperature ranging from 20° C. to 80° C.
3. Method according to claim 1, wherein the catalyst is the Schwartz's reagent of formula (C.sub.5H.sub.5).sub.2ZrHCl).
4. Method according to claim 1, wherein the catalyst is used in an amount ranging from 0.5% to 20%, in molar percentage.
5. Method according to claim 1, wherein the aminoborane of formula BH.sub.2—N(R.sub.1).sub.2 is formed in situ by a dehydrogenation reaction of an amine-borane complex of formula H.sub.3B←NH(R.sub.1).sub.2.
6. Method for the preparation of an alkenylaminoborane of formula (I) according to claim 1, wherein the compound of formula (I) is selected from the group consisting of the following structures: ##STR00105## ##STR00106##
7. Method for the preparation of an alkenylaminoborane of formula (I) according to claim 1, wherein a compound selected from the group consisting of a terminal alkyne, diisopropylaminoborane (DIPOB) or dicyclohexylaminoborane (DICOB) and a catalyst selected from the group consisting of Schwartz's reagent (Cp.sub.2ZrHCl), dicyclohexylborane (HBCy), diisopinocamphenylborane (HBipc2), 9-borabicyclo(3.3.1) nonane (9-BBN), are used for the implementation of said method.
8. Method for the preparation of an alkenylaminoborane of formula (I) according to claim 1 for the preparation of one of the compounds of formulas (II), (III) or (IV) below: ##STR00107## wherein R and n have the meanings given in claim 1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5, are identical or different and represent hydrogen, linear or branched alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl groups, or aromatic or non-aromatic heterocyclic groups, with 1 to 18 carbon atoms, optionally bearing at least one substituent, where said substituents are chosen from a linear, branched or cyclic alkyl groups of 1 to 18 carbon atoms, and halogens F, Cl, Br and I, where R.sub.2 and R.sub.3 can be linked to form together a cycle, by implementing a one-pot method.
9. Method for the preparation of an alkenyldiaminoborane compound of formula (II): ##STR00108## in which R and n have the meanings given in claim 1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are identical or different and represent hydrogen, linear or branched alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl groups, or aromatic or non-aromatic heterocyclic groups, with 1 to 18 carbon atoms, optionally bearing at least one substituent, where said substituents are chosen from a linear, branched or cyclic alkyl groups of 1 to 18 carbon atoms, and halogens F, Cl, Br and I, where R.sub.2 and R.sub.3 can be linked to form together a cycle, by implementing a one-pot method, comprising the following steps: a) a step of preparing an alkenylaminoborane of formula (I) according to claim 1, b) a step of alcoholysis by an alcohol R′—OH of the alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula (IM): ##STR00109## the alcohol R′—OH is chosen from MeOH, EtOH, PrOH or iPrOH, c) a step of substituting the alkoxyl groups R′O of the compound of formula (IM) with an amino group comprising the groups R.sub.2, R.sub.3, R.sub.4 and R.sub.5 where R.sub.2, R.sub.3, R.sub.4, and R.sub.5 have the meanings indicated above, making it possible to obtain the compound of formula (II), d) optionally a purification step.
10. Method for the preparation of an alkenyldiaminoborane compound according to claim 9, wherein said amino group is diaminonaphthalene of the following formula: ##STR00110##
11. Method for the preparation of an alkenylboronate compound of formula (III): ##STR00111## wherein R and n have the meanings given in claim 1, R.sub.2 and R.sub.3 are identical or different and represent hydrogen, linear or branched alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl groups, or aromatic or non-aromatic heterocyclic groups, with 1 to 18 carbon atoms, optionally bearing at least one substituent, where said substituents are chosen from a linear, branched or cyclic alkyl groups of 1 to 18 carbon atoms, and halogens F, Cl, Br and I, where R.sub.2 and R.sub.3 can be linked to form together a cycle, by implementing a one-pot method, comprising the following steps: a) a step of preparing an alkenylaminoborane of formula (I) according claim 1; b) a step of alcoholysis by an alcohol R′—OH of the alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula (I-M): ##STR00112## the alcohol is chosen from MeOH, EtOH, PrOH or iPrOH; c) a step of substituting the alkoxyl groups R′O of the compound of formula (I-M) with an alcohol or diol comprising R.sub.2 and R.sub.3 groups, by a reaction of transesterification; d) optionally a purification step.
12. Method for the preparation of an alkenylboronate compound of formula (III) according to claim 11, wherein said diol used is pinacol or neopentylglycol.
13. Method for the preparation of an alkenylfluoroborate compound of formula (IV): ##STR00113## wherein R and n have the meanings indicated in claim 1, comprising the following steps: a) a step of preparing an alkenylaminoborane of formula (I) according to claim 1; b) a step of alcoholysis by an alcohol R′—OH of the alkenylaminoborane of formula (I) into an intermediate alkenylboronate of formula (I-M): ##STR00114## the alcohol R′—OH is chosen from MeOH, EtOH, PrOH or iPrOH; c) a step of substituting the alkoxyl groups R′O of the compound of formula (I-M) with a fluorinated group; d) optionally a purification step.
14. Method for the preparation of one of the compounds of formulas (II), (III) or (IV) according to claim 9, corresponding to one of the following structures: ##STR00115## ##STR00116## ##STR00117##
15. Method according to claim 1, wherein the compounds of formulas (I), (II), (III) or (IV), as reaction intermediate compounds, are used for the implementation of stereoselective, multistep or coupling syntheses, selected from the group consisting of Suzuki-Miyaura, Chan-Lam, Petasis and halogenation reactions.
16. Method according to claim 2, wherein the catalyst is the Schwartz's reagent of formula (C.sub.5H.sub.5).sub.2ZrHCl).
17. Method according to claim 2, wherein the catalyst is used in an amount ranging from 0.5% to 20%, in molar percentage.
18. Method according to claim 3, wherein the catalyst is used in an amount ranging from 0.5% to 20%, in molar percentage.
19. Method according to claim 2, wherein the aminoborane of formula BH.sub.2—N(R.sub.1).sub.2 is formed in situ by a dehydrogenation reaction of an amine-borane complex of formula H.sub.3B←NH(R.sub.1).sub.2.
20. Method according to claim 3, wherein the aminoborane of formula BH.sub.2—N(R.sub.1).sub.2 is formed in situ by a dehydrogenation reaction of an amine-borane complex of formula H.sub.3B←NH(R.sub.1).sub.2.
Description
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0195] Experimental Part
Example 1: Preparation of Alkenylaminoboranes of Formula (I): General Protocol for the Preparation of Alkenylaminoboranes
[0196] The alkenylaminoboranes of formula (I) are prepared according to the following scheme:
##STR00025##
[0197] To a solution of terminal alkyne (10 mmol, 1 eq) and of DIPOB (10 mmol, 1.1 eq) in 20 mL of MTBE, is added the Schwartz's reagent in a catalytic quantity (12 mol %).
[0198] The mixture is brought to 70° C. for 4 hours.
[0199] The products are analyzed by .sup.1H and .sup.11B NMR.
[0200] Conversion Rate:
[0201] The conversion is relative to the disappearance of the alkyne.
[0202] The conversion rate is determined using the .sup.1H NMR signals by comparison between the signals of the protons of the alkyne not involved during the reaction which serve as a reference and the signal of the propargyl proton.
[0203] Thus a total conversion of 100% corresponds to the total disappearance of the quantity of starting alkyne introduced, indicating that all the alkynes have been transformed during the method.
[0204] Tests were carried out with several terminal alkynes having different R groups and the results of the conversion rate of the alkynes are reported in Table 1.
[0205] For compound I-I, the degree of conversion (*) is 92% when the reaction is carried out for 4 hours and 100% when the reaction is carried out for 8 hours.
TABLE-US-00001 TABLE 1 Alkenylaminoboranes of formula (I) Compound Structure Conversion (%) I-a
Example 2: Preparation of Alkenyldiaminoboranes of Formula (II) with Diaminonaphthalene (Dan)
[0206] The alkenyldiaminoboranes are prepared according to the following scheme:
##STR00043##
[0207] The alkenylaminoborane of formula (I) is prepared according to Example 1 then:
[0208] 1. a methanolysis (3 equiv.) is carried out at low temperature (−40° C.), for 1 hour, in order to form the intermediate methyl alkenylboronate;
[0209] 2. the intermediate is subjected to substitution of the methoxyl groups by diaminonaphthalene (dan) in the presence of FeCl.sub.3 and imidazole in a solvent mixture MeCN:H.sub.2O (1:1) at room temperature (RT) for 4 hours.
[0210] Tests were carried out with several terminal alkynes having different R groups.
[0211] The results of the conversion rate of the alkynes and the yield after purification by column chromatography (silica gel) are reported in Table 2.
TABLE-US-00002 TABLE 2 Alkenyldiaminoboranes of formula (II) prepared with diaminonaphthalene (dan) Compound Structure Conversion (%) Yield (%) II-a
Example 3 Preparation of Alkenylboronates of Formula (III) with Pinacol
[0212] The alkenylboronates of formula (III) with pinacol are prepared according to the following scheme:
##STR00055##
[0213] The alkenylaminoborane of formula (I) is prepared according to Example 1 then:
[0214] 1. a methanolysis (3 equiv.) is carried out at low temperature (−40° C.), for 1 hour, in order to form the intermediate methyl alkenylboronate;
[0215] 2. the intermediate is transesterified by adding a solution of pinacol in diethyl ether at −40° C., the solution being brought from −40° C. to room temperature (RT), for 4 hours: the methoxyl groups are substituted by pinacol (pin).
[0216] Tests were carried out with several terminal alkynes having different R groups.
[0217] The results of the degree of conversion of the alkynes and the yield after washing of the products without a purification step are reported in Table 3.
TABLE-US-00003 TABLE 3 Alkenylboronates of formula (III) prepared with pinacol Compound Structure Conversion (%) Yield (%) III-a
Example 4: Preparation of Alkenylboronates of Formula (III) with Neopentylglycol
[0218] The alkenylboronates of formula (III) with neopentylglycol are prepared according to the following scheme:
##STR00067##
[0219] The alkenylaminoborane of formula (I) is prepared according to Example 1 then:
[0220] 1. a methanolysis (3 equiv.) is carried out at low temperature (−40° C.), for 1 hour, in order to form the intermediate methyl alkenylboronate;
[0221] 2. the intermediate is transesterified to allow the substitution of the methoxyl groups by neopentylglycol (neo): the neopentylglycol is added in solution in diethyl ether at −40° C. and the solution is brought from −40° C. to room temperature (RT), for 4 hours.
[0222] Tests were carried out with several terminal alkynes having different R groups.
[0223] The results of the degree of conversion of the alkynes and the yield after washing of the products without a purification step are reported in Table 4.
TABLE-US-00004 TABLE 4 Alkenylboronates of formula (III) prepared with neopentylglycol (neo) Compound Structure Conversion (%) Yield (%) III-l
Example 5: Preparation of Alkenylfluoroborates of Formula (IV)
[0224] The alkenylfluoroborates of formula (IV) are prepared according to the following scheme:
##STR00076##
[0225] The alkenylaminoborane formula (I) is prepared according to Example 1 then:
[0226] 1.a methanolysis (3 equiv.) is carried out at low temperature (−40° C.), for 1 hour, in order to form the intermediate methyl alkenylboronate;
[0227] 2. the intermediate methyl alkenylboronate is transformed into the potassium trifluoroborate salt by substitution of the methoxyl groups, in the presence of a solution of KHF.sub.2 prepared in methanol at −40° C.; the solution is brought from −40° C. to ambient temperature (RT), for 4 h.
[0228] Tests were carried out with several terminal alkynes having different R groups.
[0229] The results of the conversion rate of alkynes and the yield after precipitation in acetone using diethyl ether are reported in Table 5.
TABLE-US-00005 TABLE 5 Alkenylfluoroborates of formula (IV) Com- Conversion Yield pound Structure (%) (%) IV-a
Example 6 Synthesis of Alkenylaminoboranes of Formula (I) from DIPOB Generated in Situ
[0230] The alkenylboronates of formula (III) are prepared with neopentylglycol from alkenylaminoboranes of formula (I) obtained from DIPOB generated in situ according to the scheme following, steps 1. and 2. being carried out according to the protocol of example 4:
##STR00081##
[0231] The tests carried out with Fluorenol, Lynestrenol and 4-Phenyl-1-butyne as alkyne, involving the in situ generation of DIPOB via the dehydrogenation of DIPAB in the presence of PhMgBr (5 mol %), allowed quantitative yields, respectively of 92%, 86% and 96%.
Example 7 Stereoselective Synthesis of Bromoalkenes from the Intermediate of Formula (I)
[0232] Preparation of the bromoalkenes (E) The preparation of the bromoalkenes (E) from the intermediate of formula (I) is carried out according to the following scheme:
##STR00082##
[0233] The alkenylaminoborane of formula (I) prepared according to Example 1 undergoes:
[0234] 1. methanolysis (3 equiv.) at low temperature (−78° C.) for 1 hour to form the intermediate methyl alkenylboronate;
[0235] 2. Bromination in the presence of CuBr2 in a THF:H20 (1:1) mixture at 70° C. for 16 h.
[0236] Tests were carried out with several terminal alkynes having different R groups.
[0237] The ratio (Z:E) obtained and the yield after purification on silica gel are reported in Table 6.
TABLE-US-00006 TABLE 6 Bromoalkenes (E) obtained from the alkenylaminoborane intermediate of formula (I) Compound Structure (Z:E) Yield (%) V-a
[0238] Preparation of Bromoalkenes (Z)
[0239] The preparation of the bromoalkenes (Z) from the intermediate of formula (I) is carried out according to the following scheme:
##STR00092##
[0240] The alkenylaminoborane of formula (c) is prepared according to Example 1 then:
[0241] 1. Dibromine Br.sub.2 in solution in MTBE at 0° C. is added and the solution is maintained at 0° C. for one hour;
[0242] 2. MeONa at 0° C. is added and the solution is maintained at 0° C. for 2 h.
[0243] Tests were carried out with several terminal alkynes having different R groups.
[0244] The ratio (Z:E) obtained and the yield after purification on silica gel are reported in Table 6.
TABLE-US-00007 TABLE 7 Bromoalkenes (E) obtained from the alkenylaminoborane intermediate of formula (I) Compound Structure (Z:E) Yield (%) VI-a