1,2-Silyl-Migrative Cyclization of Vinylsilanes Bearing a Hydroxy Group:  Stereoselective Synthesis of Multisubstituted Tetrahydropyrans and Tetrahydrofurans¹

Abstract

Acid-catalyzed intramolecular addition of a hydroxy group to alpha-alkylated vinylsilanes has been studied. Treatment of (Z)-5-alkyl-5-silyl-4-penten-1-ols 1 (R = alkyl) with 5 mol % TiCl(4) in CHCl(3) gave trans-2-alkyl-3-silyltetrahydropyrans 2 exclusively (trans/cis = >99/1 to 97/3). The cyclization efficiency and rate strongly depended on the geometry of the C-C double bond and the silyl group. The use of (E)-vinylsilanes resulted in lower yields with poor cis-selectivity. In the cyclization of (Z)-1 (R = Bu), the silyl group used, the reaction time, and the yield of 2 were as follows: SiMe(2)Ph, 9.5 h, 75%; SiMe(3), 7.5 h, 66%; SiMePh(2), 24 h, 58%; SiMe(2)-t-Bu, 0.75 h, 85%; SiMe(2)Bn, 1.5 h, 78%. This 1,2-silyl-migrative cyclization could be applied to stereoselective synthesis of trisubstituted tetrahydropyrans. The acid-catalyzed reaction of 1-, 2-, or 3-substituted (Z)-5-silyl-4-nonen-1-ols 8 gave r-2,t-3,c-6-, r-2,t-3,t-5-, or r-2,t-3,c-4-trisubstituted tetrahydropyrans with high diastereoselectivity, respectively. (Z)-4-Alkyl-4-silyl-3-buten-1-ols 5 as well as 1 underwent the 1,2-silyl-migrative cyclization to give 2-alkyl-3-silyltetrahydrofurans 6 with high trans-selectivity. This silicon-directed cyclization was also available for the stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans.

Nucleophilic Substitution Reactions of 2‐Phenylthio‐Substituted Carbohydrate Acetals and Related Systems: Episulfonium Ions vs. Oxocarbenium Ions as Reactive Intermediates

“…When silane 47, which closely resembles sulfide 45, was treated with a Lewis acid, a comparable ring expansion by a 1,2-rearrangement occurred (Scheme 13). [55] This reaction was also stereospecific. The essential features of this reaction are the same as for the sulfide: (1) the leaving group departs anti to the silyl group, (2) migration of the silyl group is suprafacial, and (3) nucleophilic attack occurs anti to the silyl group.…”

Reactivity, Selectivity, and Synthesis of 4‐C‐Silylated Glycosyl Donors and 4‐Deoxy Analogues

“…The mechanistic background for the formation of vinyl furanosides was not investigated in‐depth. Nevertheless, our observations suggest that the β‐cationic stabilization from the silyl‐group results in the electrophilic substitution of an unsaturated allylic silane [5, 41, 42] through a two‐step mechanism related to a 1,2‐silyl migration or 1,3‐silyl rearrangement followed by anti ‐elimination, not unlike a Peterson‐olefination [13, 43, 44] . This would explain why inversion of the 4‐position was observed.…”

“…Nevertheless, our observations suggest that the b-cationic stabilization from the silyl-group results in the electrophilic substitution of an unsaturated allylic silane [5,41,42] through a two-step mechanism related to a 1,2-silyl migration or 1,3-silyl rearrangement followed by anti-elimination, not unlike a Peterson-olefination. [13,43,44] This would explain why inversion of the 4-position was observed. It is noteworthy that the formation of vinyl furanosides also was observed by Imperio et al during their synthesis of 6-boronic acid sugar derivatives.…”

Silicon- and sulfur-mediated synthesis of benzoannulated cyclooctanols

“…The hydroxy group of compound 4 is converted 16 into THPether 5 17 by acid-catalyzed addition to 3,4-dihydro-2H-pyran. Desilylation with TBAF provides alcohol 6 18 which is oxidized to the corresponding aldehyde 7 19 using IBX 20 in DMSO.…”