Tris(trimethylsilyl)silyl Group for Diastereoselective and Sequential Reactions

The tris(trimethylsilyl)silyl group, also called the sisyl, hypersilyl and super silyl group, has been described in a variety of diastereoselective and sequential reactions. Super silyl enol ethers were initially found to succeed in 2 + 2 cyclizations with acrylates catalyzed by bis(2,6-diphenylphenoxide) aluminum triflimide. While a number of super silyl enol ethers perform exceedingly well in this 2 + 2 cyclization reaction and many diastereoselective reactions, the super silyl enol ether of acetaldehyde has proven particularly useful. This reagent allows for the direct installation of the acetaldehyde moiety via a Mukaiyama aldol reaction. Triflimide (HNTf 2) is used as the initiator at a loading of 0.05--0.10 mol%. The reaction can be sequentially followed with other acid-catalyzed reactions termed sequential aldol (SA) reactions. These include the addition of silyl enol ethers for SAA reactions and the Rawal-Kozmin amino siloxy diene for SA-hetero Diels-Alder cyclizations. The low Bronsted acid loading allows for sequential reactions employing basic conditions as well. To this end, SA-Grignard reactions succeeded in three- and four-component reactions generating relatively complex chiral architecture from extremely simple starting materials. Importantly, use of Grignards in combination with ketone-derived super silyl enol ethers generates tertiary carbinols with especially high diastereoselectivity.