Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

JAS Grigiarà ddition of trimethylsilyïmethy~ chionde to Cbz-G
Ser(ald)-OBO ester 337: 1-[N-~~10xycsrieony1)-(~1-smin012-bydn,~-3-(1,1,1-
trimetbylsilyl)-propy1]4meth-yI-2,6,7-~o~bicyd~2~ ]octane, Cbz-LlSer-
(CH2TMS)-OB0 ester, 3.45.
Cnide Cbz-Ser(a1d)-OB0 ester 3.37 (0.40 g, 1.25 mm01 assuming 100% yield of the
ddehyde from the oxidation) was dissolved in dry THF (40 mL) to which
trimethylsilylmethylmagnesium chloride (5.0 mL, 5.0 mrnol, 1 .O M in EtzO) was added
by syringe. The mixture was refiuxed under Ar for 6 h before 3% mC1 (20 mL) was
added and the mixture then extracted with EtOAc (3 x 50 mL). The organic fractions
were pooled and then extracted with with 3% mC1 (2 x 25 mL), 10 % NaHC03 (25
mL), saturated NaCl (25 mL) and dried over MgS04. The solvent was removed in vacuo
and the resulting oil purified by flash chromatography to give 0.368 g (72% yield) of a
clear oil.
TU3 (Et0AC:Hex) Rr = 0.58; 'H NMR (CDCb, 250 MHz) 6 7.40-7.26 (m, SH, ArH),
5.32 (d, lH, J = 10.3Hz, NH), 5.12 (s, 2H, CbzCm), 4.31 (dd, lH, J = 4.8, 9.7Hz, B-
CH), 3.89 (s, 6H, OBO ester CH20), 3.68 (d, 1 H, J = 10.3Hz, a-CU), 0.85 (dd, 1 H, J =
9.6. 14.7Hz, y-CHH), 0.78 (s, 3H, OB0 ester CC&). 0.60 (dd, 1 H, J = 4.7, 14.7Hz, y-
CHH), 0.02 (s, 9H, Si(CH3),); "C NMR (CM3I3, 63 MHz) 6 157.2 (CONH), 136.7
(-=), 128.6, 128.5, 128.2 (=-Fi), 108.9 (OB0 ester C-O), 72.8 (OB0 ester m),
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