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US 6,605,745 B2Granted
Synthesis of P-chiral bisphospholane ligands and their transition metal complexes for use as asymmetric hydrogenation catalysts
OwnerGarrett Stewart Hoge, II, Om Prakash Goelinventors
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Abstract
P-chiral bisphospholane ligands and methods for their preparation are described. Use of metal/P-chiral bisphospholane complexes to catalyze asymmetric transformation reactions to provide high enantiomeric excesses of formed compounds is also described.
Claims10
The P-chiral ligand of the formula
- and its corresponding enantiomer, wherein:
- R is an alkyl, fluoroalkyl, or perfluoroalkyl group each containing up to about 8 carbon atoms, a carboxylic acid group, a carboxylic ester group, an aryl group, a substituted aryl group, an aralkyl group, or a ring substituted aralkyl group;
- and
- Bridge is a —(CH2)n— where n is an integer from 1 to 12, a 1,2-divalent phenyl, or a 1,2-divalent substituted phenyl.
1 more element
A chiral ligand of the formula
- and its corresponding enantiomer, wherein:
- R is an alkyl, fluoroalkyl, or perfluoroalkyl group each containing up to about 8 carbon atoms, a carboxylic acid group, a carboxylic ester group, an aryl group, a substituted aryl group, an aralkyl group, or a ring substituted aralkyl group;
- and
- each Y is independently halogen, alkyl, alkoxy, aryl, aryloxy, nitro, amino, vinyl, substituted vinyl, alkynyl, or sulfonic acid and n is an integer from 0 to 4 equal to the number of unsubstituted aromatic ring carbons.
1 more element
A method for forming a chiral ligand of the formula
- and its corresponding enantiomer, wherein:
- R is an alkyl, fluoroalkyl, or perfluoroalkyl group each containing up to about 8 carbon atoms, a carboxylic acid group, a carboxylic ester group, an aryl group, a substituted aryl group, an aralkyl group, or a ring substituted aralkyl group;
- comprising the steps of:
- (a) reacting a compound of the formula R1OH, wherein R1 is a branched alkyl, an aryl group, a substituted aryl group, an aralkyl group, a ring substituted aralkyl group, with a phosphorous trichloride forming an intermediate of the formula
- wherein R1 is defined above;
- (b) reacting intermediate II with a divalent alkyl di-Grignard solution and a borane methyl sulfide complex forming an intermediate of the formula
- wherein R1 is defined above;
- (c) reacting intermediate III with a chiral base comprising a compound of the formula R3Li, wherein R3 is an alkyl, an aryl, an alkylamide, or an alkylamine, (−)-sparteine, and an electrophile, wherein the electrophile is an alkyl halide, carbon dioxide, an aldehyde, a ketone, a carboxylic ester, a carbonate, a silyl chloride, or an alkyl sulfonate, forming an intermediate of the formula
- or its corresponding enantiomer, wherein R and R1 are defined above;
- (d) reacting intermediate IV, or its corresponding enantiomer, wherein R and R1 are defined above with a methyl anion compound forming an intermediate of the formula
- or its corresponding enantiomer, wherein R is defined above;
- (e) reacting intermediate Va, or its corresponding enantiomer, wherein R is defined above, with an oxidative coupling agent forming an intermediate VIa,
- or its corresponding enantiomer, wherein R is defined above;
- and
- (f) reacting intermediate Via, or its corresponding enantiomer, wherein R is defined above, in a borane removing mixture to form the chiral ligand of Formula Ia, or its corresponding enantiomer.
12 more elements
A method for forming a chiral ligand of the formula
- and its corresponding enantiomer, wherein:
- R is an alkyl, fluoroalkyl, or perfluoroalkyl group each containing up to about 8 carbon atoms, a carboxylic acid group, a carboxylic ester group, an aryl group, a substituted aryl group, an aralkyl group, or a ring substituted aralkyl group;
- comprising the steps of:
- (a) reacting a compound of the formula
- or its corresponding enantiomer, wherein R is defined above, with a compound of the formula
- wherein R1 is an alkyl and n is 1, forming an intermediate of the formula
- or its corresponding enantiomer, wherein R and R1 are defined above;
- (b) heating the compound of the Formula 11, or its corresponding enantiomer, wherein R and R1 are defined above, in dimethyl sulfoxide forming an intermediate of the formula
- or its corresponding enantiomer, wherein R is defined above;
- (c) reacting the compound of the Formula 12, or its corresponding enantiomer, wherein R is defined above, with LAH forming an intermediate of the formula, or its corresponding enantiomer,
- wherein R is defined above;
- (d) reacting the compound of the Formula 13, or its corresponding enantiomer, wherein R is defined above, with Et3N and methanesulfonyl chloride forming an intermediate of the formula
- or its corresponding enantiomer, wherein R is described above;
- (e) reacting the compound of the formula 14, or its corresponding enantiomer, wherein R is defined above, with methylphosphine borane forming an intermediate of the formula
- or its corresponding enantiomer, wherein R is defined above;
- (f) reacting intermediate 17, or its corresponding enantiomer, wherein R is defined above, with an oxidative coupling agent forming an intermediate of the formula
- or its corresponding enantiomer, wherein R is defined above;
- and
- (g) reacting intermediate VIc, or its corresponding enantiomer, in a borane removing mixture to form the chiral ligand of formula Ib, or its corresponding enantiomer.
16 more elements
A method for forming a chiral ligand of the formula
- wherein:
- R is an alkyl, fluoroalkyl, or perfluoroalkyl group each containing up to about 8 carbon atoms;
- a carboxylic acid group;
- a carboxylic ester group;
- an aryl group;
- a substituted aryl group;
- an aralkyl group;
- or a ring substituted aralkyl group;
- and
- each Y is independently, halogen, alkyl, alkoxy, aryl, aryloxy, nitro, amino, vinyl, substituted vinyl, alkynyl, or sulfonic acid and n is an integer from 0 to 4 equal to the number of unsubstituted aromatic ring carbons;
- comprising the steps of:
- (a) reacting a bis(primary phosphine) having a structural formula of
- in the presence of a base of the formula R4Li, wherein R4 is an alkyl, aryl, alkylamide, alkylamine, or the bases sodium amide, potassium amide, potassium hydroxide, or sodium hydroxide with a compound of the formula
- forming an intermediate of the formula
- (b) reacting the intermediate of the formula
- with a chiral base comprising a compound of the formula R3Li, wherein R3 is an alkyl, an aryl, an alkylamide, or an alkylamine, (−)-sparteine, and an electrophile, wherein the electrophile is an alkyl halide, carbon dioxide, an aldehyde, a ketone, a carboxylic ester, a carbonate, a silyl chloride, or an alkyl sulfonate, forming an intermediate of the formula
- or its corresponding enantiomer, wherein R is defined above;
- and
- (c) reacting intermediate Xa in a borane removing mixture to form the chiral ligand of the Formula VIIa.
16 more elements
Dependencies are inferred from the claim text.