TY - JOUR

T1 - Asymmetric nucleophilic acylation of aldehydes via 1,1-heterodisubstituted alkenes

AU - Monenschein, Holger

AU - Dräger, Gerald

AU - Jung, Alexander

AU - Kirschning, Andreas

PY - 1999/7/22

Y1 - 1999/7/22

N2 - 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 α-hydroxy methyl esters (7-37%). Use of the corresponding sulfoxide 24 or sulfon 25 led to an improved chemical yield of α-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.

AB - 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 α-hydroxy methyl esters (7-37%). Use of the corresponding sulfoxide 24 or sulfon 25 led to an improved chemical yield of α-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.

KW - Aldehydes

KW - Asymmetric synthesis

KW - C-C coupling

KW - Dihydroxylations

KW - Wittig reactions

UR - http://www.scopus.com/inward/record.url?scp=0040909104&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1521-3765(19990802)5:8<2270::AID-CHEM2270>3.0.CO;2-L

DO - 10.1002/(SICI)1521-3765(19990802)5:8<2270::AID-CHEM2270>3.0.CO;2-L

M3 - Article

AN - SCOPUS:0040909104

VL - 5

SP - 2270

EP - 2280

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 8

ER -