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Boc
TMS
N
H
Bn
64f
tert-Butyl-1-((4-(trimethylsilyl)but-3-yn-2-yloxy)carbonyl)-2-phenylethylcarbamate (64f).
Prepared by following general procedure C using: 4-trimethylsilylbut-3-yn-2-ol (6.0 g, 4.2
mmol), DMAP (200 mg, 1.64 mmol), DCC (8.7 g, 4.2 mmol), N-Boc-phenylalanine (11.2 g,
4.23 mmol) Yield 64f (16.4 g, >95%). The compound was immediately used in the next Claisen
rearrangement step.
General procedure D for preparation of 65a-65c via a Claisen rearrangement.
Bu
MeO 2C
•
65b
O
H
O
NHCbz
2-Benzyloxycarbonylamino-3-butyl-2,6-dimethylhepta-3,4-dienoic acid methyl ester (65b).
General procedure for preparation of a THF solution of LDA: i-Pr2NH (5.1 mmol) was added to
a flame dried 100 mL round-bottomed flask, followed by THF (10 mL) under nitrogen
atmosphere. The reaction flask was cooled to -20 °C and n-BuLi (5.1 mmol of 1.6 M solution in
hexanes) was added dropwise over 5 min. The colorless solution was then cooled to -78 °C and
held at that temperature for 30 min.
Step 1. Ester-enolate Claisen rearrangement: To a freshly prepared solution of LDA (5.1 mmol)
in THF (10 mL) was added 64b (730 mg, 2.04 mmol) in THF (10 mL) at -78 °C. After 2 min of
stirring, ZnCl2 (4.9 mL of a 0.5 M solution in THF, 2.4 mmol) was added at -78 °C. The reaction
mixture was allowed to warm to rt over 10 h. The reaction mixture was then poured in Et2O (100
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