Novel Synthesis of Trisubstituted Olefins for the Preparation of the C16–C30 Fragment of Dolabelide C

Abstract

A silicon-tether ring-closing metathesis strategy is reported for the synthesis of trisubstituted olefins flanked by allylic or homoallylic alcohols, which are difficult to obtain by classical ring-closing or cross-metathesis reactions. In addition, a novel Peterson olefination reaction has been developed for the preparation of the allyldimethylsilane precursors, which are versatile synthetic intermediates. This method was then applied to the synthesis of the C16–C30 fragment of dolabelide C.

Diastereoselective synthesis of trisubstituted olefins using a silicon-tether ring-closing metathesis strategy

“…Furthermore, we envisioned a novel Peterson olefination for the synthesis of allyldimethylsilanes 9a-c from esters 4a-c, which would proceed in an analogous fashion as the for-mation of allyltrimethylsilanes 5a-c (Scheme 5). As previously reported in our communication, 10 both steps proceeded uneventfully (Scheme 8). It is worth noting that this new olefination reaction provides an easy access to allyldimethylsilanes, but also to the corresponding chlorosilanes (see Scheme 7).…”

“…As previously reported in our communication, 10 this new synthetic route was applied to the synthesis of the C16-C30 fragment of dolabelide C.…”

“…We then prepared several allylic bromides with a gem-disubstituted olefin, which are models or racemic versions of the side chain of dolabelide C, by a known method. 15 Esters 4a-c 10 were subjected to trimethylsilylmethylmagnesium chloride in the presence of anhydrous cerium trichloride, and the resulting β-hydroxysilanes were stirred with silica gel in dichloromethane to furnish trimethylsilanes 5a-c in 61-91% yield (Scheme 5). Bromination of the Peterson olefination products 5a-c was performed with pyrrolidone hydrotribromide 6 in THF to give the allylic bromides 7a-c in 88-91% yield.…”

“…As previously reported, direct cleavage was attempted on 10b with diverse fluoride sources and Lewis acids, but without success, leading to isomerisation product 13b′ or elimination products 14b and 14b′ (see Table 1 for structures of these compounds). 10 We thus resorted to a two-step process, starting with cleavage of the silicon-oxygen bond with methyllithium to give allyltrimethylsilanes 11a-c (Scheme 9).…”

“…9 We propose a strategy for an efficient and diastereoselective synthesis of trisubstituted olefins flanked by an allylic alcohol, which involves a RCM reaction with a O-Si-C tether. In our preliminary communication, 10 the metathesis precursors C were prepared by dehydrogenative coupling of allylic alcohols A and allyldimethylsilanes B, and the metathesis products D were converted into the E olefin (Scheme 2). Herein, we report our preliminary attempts to synthesise compounds C and a synthesis of versatile allylchorodimethylsilanes from silanes B.…”