Synthesis of Cyclic Alkenyl Dimethylsiloxanes from Alkynyl Benzyldimethylsilanes and Application in Polyene Synthesis

Abstract

Cyclic dimethylalkenylsiloxanes, useful motifs for (Z)-selective Hiyama cross-coupling, are accessed from alkynyl benzyldimethylsilanes featuring adjacent allylic or homoallylic oxygen substituents by semihydrogenation/ debenzylation/cyclization. While formation of 5-and 6membered rings can be achieved from the free alcohols using fluoride or silanolate, allylic acetate precursors to 5-membered rings display distinct modes of activation. The utility of these compounds is demonstrated through the preparation of a variety of (Z)-alkene-containing polyenes and application to a concise total synthesis of leukotriene B 3 .

Total Synthesis of the Reported Structure of Neaumycin B

“…To achieve 3,4-dimethoxybenzyl protection at the C27-OH (Scheme ), 26 was treated first with catalytic tetra- n -butylammonium fluoride (TBAF) to affect closure of the five-membered siloxane ring across C35–C37 and leave the C27-OH exposed for selective DMB protection (see Supporting Information for details). Subsequent exposure of the siloxane to methyllithium then unmasked the C35-OH to give 27 , which now serves as the directing group for the future stereoselective epoxidation.…”

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

“…Also, it is important to underscore that the copper cocatalyst was crucial for the success of this transformation as without, only protodesilylation products were obtained. This behavior is in contrast to that of dimethyl(alkenyl)siloxanes, which do not require copper to undergo cross-coupling [30,32]. This requirement for copper prompted us to test copper-catalyzed C(sp 2 )-C(sp 3 ) cross-coupling reactions, as reported by Takeda et al, to achieve allylation reactions of benzyldimethyl(alkenyl)silanes [36].…”

“…In an attempt to isolate cyclic siloxane 16, we then considered a protocol reported by Anderson and co-workers to prepare cyclic siloxanes by debenzylation/cyclization of benzyldimethysilylsubstituted allylic alcohols [32]. To that end, carbinol 4c was treated with TBAF⋅3H 2 O (1.0 equiv), which resulted in the formation of 16 in 86% yield (along with toluene, Scheme 6).…”

“…We first briefly investigated Pd-catalyzed arylation reactions (Scheme 7). Fluoride-promoted arylation of benzyldimethyl(alkenyl)silanes have been reported, and it is established that they through the cleavage of the benzyl moiety from the benzyldimethylsilyl groups, leading to either dimethylsilanols or cyclic siloxanes (as for substrates with pending hydroxy units) [32][33][34][35]. To the best of our knowledge, no analogous cross-coupling reactions from aryl-or heteroarylsubstituted benzyldimethylsilanes have been disclosed.…”

NBE-Controlled Palladium-Catalyzed Intermolecular Selective C–H Silylation of Boronic Acids

“…Organosilicons are one of the most important classes of silicon-containing organic compounds, which constitute the key structures of many natural products, pharmaceutical drugs, and functional materials (Figure ). Specifically, the recently emerging studies in medicinal chemistry have been made toward the incorporation of silicon groups into drug candidates .…”