The 5-exo-dig Cyclization of Bmdms Propargylic Ethers: an Efficient Trigger for Radical Cascades

This article reviews our contribution in the field of radical synthetic chemistry, focusing on cascades relying on the use of propargylic BMDMS ethers and asymmetric synthesis using enantiopure vinylsulfoxides. THE 5-EXO-DIG CYCLIZATION OF BMDMS PROPARGYLIC ETHERS: AN EFFICIENT TRIGGER FOR RADICAL CASCADES The vinyl radical, a precious tool The vinyl radical of type 3 resulting from the highly efficient and regioselective 5-exo-dig cyclization of α-silyl radical 2, generated from bromomethyldimethylsilyl (BMDMS) propargyl ethers of type 1 has been revealed as a very versatile synthetic tool [1]. Scheme 1 illustrates different processes we have worked out over the past years. A simple stannane reduction on 3 provides heterocycles 4, which upon further addition of MeLi, give trimethylenemethane (TMM) precursors [2]. Alternatively, an oxidative treatment with H2O2 (Tamao oxidation), or Bu4NF (protodesilylation) yields valuable trisubstituted olefins [3]. All sorts of intramolecular trapping of the vinyl radical have been envisaged. The simplest is naturally a 5-exo-trig radical cyclization from 5, giving birth to a variety of cyclopentenes 6 [4]. This process is completely diastereoselective, setting the resulting methyl group and the C–O bond syn to each other. When a methallyl group, instead of an allyl group, is present, a competition between the 5exo-trig and 6-endo-trig modes of cyclization occurs. The 6-endo-trig cyclization becomes major when the vinyl radical is substituted by a phenyl group (cyclohexene 8). A final diastereoselective reduction of the methine radical installs a syn relationship between the methyl group and the C–O bond [4b]. Vinyl radicals are also very prone to engage into hydrogen transfers. A rare 1,4-H transfer (from 9) has been for instance discovered [5]. However, our most useful approaches in this domain have relied on 1,5-H transfers. An X activating group, such as a dioxolane, suitably located on the propargyl chain, promotes a 1,5-(π-exo)-H transfer from the vinyl radical 11. The translocated radical then cyclizes back in a 5-exo-trig manner to provide α-functionalized cyclopentanone derivatives 12. We have studied the diastereoselectivity of the reduction of the final β-silyl radical [6], and also investigated the possibility of developing an asymmetric version of this process, by introducing a homochiral dioxolane moiety. The best de obtained reached 50% [4c]. With highly sterically encumbered (gem-diisopropyl) substrates, vinyl radical 13 ungergoes a diasteroselective 1,5-(π-endo)-H transfer with an unactivated methyl group. The resulting methylene radical then cyclizes according to the disfavored 5-endo-trig mode of cyclization, placing the R group syn to the methyl group and to the C–O bond. A diastereoselective stannane reduction of the β-silyl radical installs a cis ring junction and terminates the sequence *Lecture presented at the 13 International Conference on Organic Synthesis (ICOS-13), Warsaw, Poland, 1–5 July 2000. Other presentations are published in this issue, pp. 1577–1797. †Corresponding author: E-mail: [email protected] [7]. This sequence has proven quite general for the synthesis of cyclopentanes 14, and has constituted so far the most efficient case of 5-endo-trig cyclization in an all-carbon system [8]. 1,6-H Transfers from the vinyl radical have also been disclosed in transannular series [9] and acyclic series [10], but their synthetic versatility has not been completely exploited. AÏSSA et al. © 2000 IUPAC, Pure and Applied Chemistry 72, 1605–1613 1606