Rearrangement of epoxynitriles: a convenient homologation of acyclic and cyclic ketones to carboxylic acids.
A convenient two-step homologation of both aliphatic and aromatic ketones to the corresponding carboxylic acid has been developed. First ketones were converted to epoxynitriles with the Darzens reaction. Second, a Lewis acid mediated rearrangement of these epoxynitriles with lithium bromide was achieved to give homologated secondary alkanoic acids (as well as aryl-alkanoic) in good yields. The mechanism and the scope of the rearrangement reaction were investigated. This strategy constitutes a two-step homologation of ketones to secondary carboxylic acids.
GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, USA. neil_f_badham@gsk.com
Neil F
NF
Badham
Wilford L
WL
Mendelson
Andrew
A
Allen
Ann M
AM
Diederich
Drake S
DS
Eggleston
John J
JJ
Filan
Alan J
AJ
Freyer
Lewis B
LB
Killmer
Conrad J
CJ
Kowalski
Li
L
Liu
Vance J
VJ
Novack
Frederick G
FG
Vogt
Kevin S
KS
Webb
Jennifer
J
Yang