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and resulted in isomerization to 72 within 10 min (Cs2CO3 was chosen since it could be used as a
base for N-alkylation of 71).
Scheme 2.10 Synthesis of glycine-derived allenic amino-ester.
BocHN
68
O
OH
TMS
OH
66a
DCC, DMAP
TMS
CH2Cl2, rt, 90%
BocHN
O
69
O
1. LDA, ZnCl 2, THF, -78 o C to rt
2. KHCO 3, MeI, DMF, rt
44%
2.2.2 N-Alkylation of Allenic Amino Esters
TMS
MeO 2C
H
• TBAF, THF
pH = 7.0 buffer, rt H
H
NHBoc
79% MeO2C 70
TBAF, THF
no buffer, rt, > 95%
Me
H
71
MeO 2C
•
H
H
NHBoc
Cs 2CO 3, THF
>95%
H
H
NHBoc
72 mixture of two
double bond isomers
The next goal was to develop a general procedure for N-alkylation of the allenic amino-
esters that would introduce the alkyne component of the precursors for transition metal-catalyzed
carbocyclization reactions. It was quickly found that treatment of the amides or carbamates with
NaH in DMF at rt for 2-5 min, followed by addition of the corresponding propargylic bromide
results in clean N-alkylation. Using this protocol on the Bz-protected substrate 58a and 1-bromo-
2-butyne gave allenyne 73a in 83% yield (Table 2.3). Varying the substitution pattern of the
alkyne was important in order to study the scope of the carbocyclization reactions. Therefore,
terminally unsubstituted alkyne was incorporated via N-alkylation with propargyl bromide
affording 73b in 73% yield, whereas alkylation with 3-phenyl-1-bromopropyne gave a phenyl
substituted allenyne 73d in 89% yield. Attempts to prepare precursor 73c with a TMS group on
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