Atsuhiro Ookawa

Sodium Borohydride-t-butyl Alcohol-Methanol as an Efficient System for the Selective Reduction of Esters

Abstract Reduction of esters to the corresponding primary alcohols by metal hydrides is an important synthetic reaction.1 One may often encounter the problem of the selective reduction of esters in the presence of other functional groups such as amide, carboxylic acid or nitrile.2

Asymmetric synthesis of optically active threo- and erythro-pyrrolidinylbenzyl alcohol by the highly stereospecific arylation of (S)-proline and the subsequent highly diastereoselective reduction of the α-amino ketone

Optically active α-amino phenyl ketones in 92–94% enantiomeric excess (e.e.) were obtained from the stereospecific arylation of (S)-proline or its derivatives by Friedel–Crafts reaction or by Grignard reaction. The subsequent complementary diastereoselective reductions of the α-amino ketone afforded respectively (S)- and (R)-α-[(S)-pyrrolidin-2-yl]benzyl alcohol in 93–100% e.e. and in 100% diastereoisomeric excess. The stereochemical course of the reduction of the α-amino ketone is discussed.

Asymmetric conjugate addition of organometallic reagents in the presence of tertiary amines to chiral α,β-unsaturated amido carboxylic acids. Addition order of reagents as an unprecedented factor in the determination of the sense of asymmetric induction

Optically active 3-substituted carboxylic acids have been obtained in moderate enantiomeric excesses (e.e.) by asymmetric conjugate addition of alkyl-lithium, in the presence of tertiary amines, to chiral α,β-unsaturated amido carboxylic acids derived from (S)-proline. The presence of tertiary amine is effective in increasing both the synthetic yields and the e.e.s. A change in the addition order of tertiary amine and alkyl-lithium to the amido-carboxylic acid changes the sense of asymmetric induction.

Unusual effect of a mixed solvent on the asymmetric reduction of chiral α-keto-amides with sodium borohydride

The mixed solvent tetrahydrofuran + methanol (99 : 1) was much more effective than the individual solvents in the asymmetric reduction of chiral α-keto-amides with sodium borohydride; this solvent effect in asymmetric induction is unprecedented.

Asymmetric conjugate addition of Grignard reagents in the presence of tertiary amines to α,β-unsaturated amides derived from (S)-2-(1-hydroxy-1-methylethyl)pyrrolidine or (S)-prolinol

In the presence of tertiary amines, diastereoselective conjugate addition of Grignard reagents to α,β-unsaturated amides affords 3-substituted carboxylic acids of high enantiomeric excess (up to 89% e.e.).

Effect of Tertiary Amines on Diastereo-Selectivity of the Asymmetric Conjugate Addition of n-Butyllithium to α,β-Unsaturated Amide Derived from (S)-Proline

Abstract Increasing interest has been centered upon asymmetric synthesis of β-substituted carboxylic acids by the conjugate addition of organometallic reagents to α,β-unsaturated systems.1 Recently Mukaiyama and Iwasawa reported the asymmetric addition of Grignard reagents to α,β-unsaturated amides derived from chiral aminoalcohol 1-ephedrine.2

Highly stereospecific arylation of (S)proline and complementary highly diastereoselective reduction of the α-amino ketone. Asymmetric synthesis of (1S,2′S)- and (1R,2′S)-phenyl(2′-pyrrolidinyl)methanol

Both optically active threo- and erythro-phenyl(2′-pyrrolidinyl)methanol (93–100% enantiomeric excess, 100% diastereoisomeric excess) were synthesised from (S)-proline by a stereospecific arylation and the subsequent complementary diastereoselective reduction of the α-amino ketone.

Complementary catalytic asymmetric induction in the enantioselective addition of diethylzinc to aldehydes

Both enantiomers of sec-alcohols were obtained in high enantiomeric excess (up to 92%) from the enantioselective addition of diethylzinc to aldehydes using chiral pyrrolidinylmethanol derivatives as catalysts.

Novel functional group selectivity in reductions with lithium borohydride in mixed solvents containing methanol

Primary amides were reduced selectively in the presence of carboxylic acid salts or secondary aliphatic amides by lithium borohydride in diglyme–methanol, and esters and epoxides were selectively reduced rapidly by LiBH4 in the presence of nitro, chloro, or amide groups in ether containing a small amount of methanol.