Practical asymmetric conjugate alkynylation of Meldrum's acid-derived acceptors: access to chiral beta-alkynyl acids.
The enantioselective conjugate addition of alkynyl nucleophiles has been a long-standing challenge in synthetic chemistry. This paper describes a highly practical asymmetric conjugate alkynylation of Meldrum's acid-derived acceptors using cinchonidine (<$100/kg) as the chiral mediator. The process provides practical access to chiral beta-alkynyl acids. Noteworthy attributes of the method are its broad scope, high functional-group compatibility, and ease of scalability.
Cui
Sheng
S
Department of Chemical Process Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. scui@amgen.com
Walker
Shawn D
SD
Woo
Jacqueline C S
JC
Borths
Christopher J
CJ
Mukherjee
Herschel
H
Chen
Maosheng J
MJ
Faul
Margaret M
MM
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D004146:Dioxanes / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000480:Alkynes; D002264:Carboxylic Acids; D004146:Dioxanes; C076489:Meldrum's acid