Novel 1,4-homofragmentation via an alpha-lactone.
Conversion of an alpha,alpha-dichloroester to the corresponding alpha-keto acid was unexpectedly complicated by a novel 1,4-homofragmentation. Investigation of the kinetics of this reaction revealed a mechanism involving an alpha-lactone intermediate, which can lead to both the desired alpha-keto acid and the 1,4-homofragmentation, with the product distribution being dependent upon reaction conditions. This information allowed development of a process that affords the alpha-keto acid exclusively and should be generally applicable to the preparation of alpha-keto acids from alpha,alpha-dichloroesters or acids.
Godfrey
Jollie D
JD
Department of Process Research and Development, Pharmaceutical Research Institute, Bristol-Myers Squibb, Post Office Box 4000, Princeton, New Jersey 08543-4000, USA. jollie.godfrey@bms.com
Fox
Rita T
RT
Buono
Frederic G
FG
Gougoutas
Jack Z
JZ
Malley
Mary F
MF
D006880:Hydroxy Acids / Q000737:chemistry*; D007651:Keto Acids / Q000737:chemistry*; D007700:Kinetics; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure
D006880:Hydroxy Acids; D007651:Keto Acids; D007783:Lactones