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esters (glycolates) thereby limiting the diversity that can be introduced at this position.
Moreover, it was reasoned that converting these carboxylic acids to esters will increase the
likelihood of a base-promoted isomerization of the allene to a 2,4-dienoic ester.
Scheme 2.1 Ester-enolate Claisen rearrangement of propargyl glycolates.
R 2
HO
O
O
R 1
LHMDS
R 2
LiO
Li
O
O
R 1
[3,3]
42 43 44
R 1 = alkyl, H
R 2 = alkyl, TMS
The corresponding Claisen rearrangement of propargylic α-amino-esters was more attractive.
Work by Castelhano and Krantz demonstrated that mild dehydrative conditions (Et3N, CCl4,
PPh3) effect the rearrangement of benzoyl protected amino ester 45 to 4-allenyl-5-oxazolone 46,
which is transformed to methyl ester 47 when treated with MeOH (Scheme 2.2). 56 Furthermore,
Kazmaier reported an ester-enolate Claisen rearrangement of variety of propargyl amino-esters
48 using LDA/ZnCl2 affording allenic amino acids 50 with diastereoselectivity greater than
93%. 57
TMSCl
Scheme 2.2 Methods for preparation of allenic amino acids.
R 3
PHN
BzHN
R 1
O
O
R 1
R 2
O
O
R 2
LDA, ZnCl 2, THF
PPh 3, CCl 4, Et 3N
MeCN
R 1
N O
Ph
•
O
R2 H
H
R 1
•
MeO 2C
45 46 47
R 3
PN
Zn
R 1
O
O
R 2
HO 2C
48 49 50
16
MeOH, HCl
[3,3] sigmatropic
rearrangement
R 3
•
HO
•
R 2
R
NHBz
1
R2 H
R
NHP
1
COOH
R2 H
P = Boc, Cbz, Tos