CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

More recently, Park et al. 170b synthesized VI (Scheme IV.4.3) starting from the
acetonide 161 derived from D-isoascorbic acid. Mesylation of 161 followed by reduction
of the ester moiety yielded mesylate diol, which was subsequently converted to the
oxirane. Addition of PhMgBr to the oxirane produced the alcohol 162. This was converted
to diolazide 163, which on treatment with 2-acetoxy-isobutyryl chloride in chloroform
followed by exposure of the resulting chloroacetate derivative to sodium methoxide
yielded VI in 60% overall yield.
O
O
HO
OH i - iv O
i, v, vi vii, viii
OH
N
O
HO 3
CO 2 Et
Ph
Ph
161 162 163
VI
(i) MsCl, pyridine; (ii) NaBH 4 , MeOH; (iii) NaH, THF, -20 °C-25 °C ; iv) PhMgBr, CuI,
THF, -40 °C-0 °C; (v) 1 N HCl, THF; (vi) CsN 3 , 18-Cr-6, PhH, Δ; (vii)
MeCO 2 C(Me) 2 COCl, CHCl 3 ; (viii) NaOMe, THF, 25 °C.
Scheme IV.4.3
IV.4.3: Present work
From retrosynthetic analysis of VI (Scheme IV.4.4) we envisaged that synselective
benzylation of 1 could be a very straightforward approach to directly generate a
carbon chain relevant to that existing in the target molecule. The homobenzylic alcohol
91a can be converted to the azide with inversion of configuration, and ultimately to the
title compound by converting its diol functionality to the epoxide. The present work
describes our detailed effort in this regard with ultimate objective to synthesize VI.
171