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.
Badham
Neil F
NF
GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, USA. neil_f_badham@gsk.com
Mendelson
Wilford L
WL
Allen
Andrew
A
Diederich
Ann M
AM
Eggleston
Drake S
DS
Filan
John J
JJ
Freyer
Alan J
AJ
Killmer
Lewis B
LB
Kowalski
Conrad J
CJ
Liu
Li
L
Novack
Vance J
VJ
Vogt
Frederick G
FG
Webb
Kevin S
KS
Yang
Jennifer
J