Chiral Synthesis via Organoboranes. 30. Facile Synthesis, by the Matteson Asymmetric Homologation Procedure, of α-Methyl Boronic Acids Not Available from Asymmetric Hydroboration and Their Conversion into the Corresponding Aldehydes, Ketones, Carboxylic Acids, and Amines of High Enan...

Article abstract of DOI:10.1021/jo00010a022

2-(α-Methylalkyl)- or 2-(α-arylethyl)-1,3,2-dioxaborinanes, RMeHC*BO2(CH2)3 (R = alkyl or aryl), of very high enantiomeric purity, not available from asymmetric hydroboration, can be prepared by the Matteson asymmetric homologation procedure of optically pure pinanediol or 2,3-butanediol boronate esters with (dichloromethyl)lithium, LiCHCl2, conveniently generated in situ in THF at -78 deg C, followed by reaction with either a Grignard reagent or an alkyllithium, with subsequent removal of the chiral auxiliaries. α-Methyl boronic esters thus obtained are readily converted into the corresponding aldehydes by the reaction with lithium (MPML) and mercuric chloride, followed by oxidation with hydrogen peroxide in a pH 8 buffer medium.The two-phase aqueous chromic acid procedure can be used to oxidize these aldehydes to the corresponding α-methyl carboxylic acids of very high enantiomeric purity without significant racemization.Additionally, pinanediol or 2,3-butanediol α-methylorganylboronate esters can be conveniently converted into borinic ester derivatives, RMeHC*BMe(OMe), of very high enantiomeric purity by reaction with methyllithium, followed by treatment with methanolic hydrogen chloride and subsequent recovery of the valuable chiral auxiliaries.These borinic ester derivatives are converted into α-methyl ketones and α-methyl primary amines of known absolute configuration by the α,α-dichloromethyl methyl ether (DCME) reaction and the reaction with hydroxylamine-O-sulfonic acid, respectively.The present synthesis of chiral 2-organyl-1,3,2-dioxaborinanes by the Matteson route, together with our direct asymmetric hydroboration procedure, makes it possible to synthesize many chiral boronic acid derivatives in very high enantiomeric purities.These complementary procedures greatly expand the scope of asymmetric synthesis via chiral organoboranes.