Asymmetric Nucleophilic Acylation of Aldehydes via 1,1-Heterodisubstituted Alkenes

Abstract

Aldehydes are asymmetrically acylated by a two step sequence that is initiated by a homologation step to 1,1-heterodisubstituted alkenes followed by asymmetric dihydroxylation. Thus, ketene O,S-acetals are efficiently prepared from aldehydes by a Peterson olefination with lithiated methoxy-phenylthiotrimethylsilyl methane 14 as the C-1 source. Although they are dihydroxylated with the Sharpless catalyst with moderate to good enantioselectivity (62 ± 80 % ee), the process is not efficient owing to the low chemical yields of the desired a-hydroxy methyl esters (7 ± 37 %). Use of the corresponding sulfoxide 24 or sulfon 25 led to an improved chemical yield of a-hydroxy methyl ester 19, but the stereoselectivity was diminished. In contrast, intermediate ketene O,O-acetals are prepared by a Horner ± Wittig reaction with phosphine oxide 31 and are dihydroxylated both with good chemical and stereochemical yield. The concept is applicable to aromatic, aliphatic, and chiral aldehydes. For example, this short sequence allows exclusive and independent preparation of both diastereomeric heptoses 69 a and 69 b.

Chemoenzymatic Preparation of Enantiomerically Enriched (R)‐(–)‐Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline

“…( R )‐(–)‐ 3c : [ α ] D 24 = –147.20 ( c = 1.00, CHCl 3 , >99 % ee ). ( R )‐(–)‐ 3d : [ α ] D 22 = –147.50 ( c = 1.28, CHCl 3 , >99 % ee ) {ref . [ α ] D 21 = –127.20 ( c = 1.00, CHCl 3 , 96 % ee )}.…”

Chiral Surfactant-Type Catalyst: Enantioselective Reduction of Long-Chain Aliphatic Ketoesters in Water

“…29 According to the general procedure B yielding Methyl 3-oxodecanoate as colourless oil 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Compound (R)-methyl 2-hydroxypentanoate 3b. 38 The organic phase was extracted with Et 2 O (5 mL×3), the organic layers were dried over Na 2 SO 4 , filtered, and the filtrate was concentrated in vacuo to give the pure light yellow oil (96 % yield). Compound (R)-methyl 2-hydroxyheptanoate 4b.…”

Synthesis of 2-hydroxymalononitrile

“…When an aldehyde or a ketone (9), an alcohol(11) and 2-hydroxymalononitrile were simply mixed in one portion, an α-hydroxyl ester(10) would be obtained in good to excellent yields [16] .…”