Chemoselective Carbonyl Allylations with Alkoxyallylsiletanes

Abstract

Alkoxyallylsiletanes are capable of highly chemo- and diastereoselective carbonyl allylsilylations. Reactive substrates include salicylaldehydes and glyoxylic acids. Chemoselectivity in these reactions is thought to arise from a mechanism involving first exchange of the alkyoxy group on silicon with a substrate hydroxyl followed by activation of a nearby carbonyl by the Lewis acidic siletane and intramolecular allylation. In this way, substrates containing multiple reactive carbonyl groups (e.g., dialdehyde or triketone) can be selectively monoallylated, even overcoming inherent electrophilicity bias.

Figure 1.

Non-catalyzed glyoxylic acid allylsilylations using allylsilacyclobutane 1.

Scheme 1.

Synthesis of allylsilacyclobutane 1 by iodine-catalyzed monoetherification and subsequent intramolecular allylation.

Scheme 2.

Scope of salicylaldehyde allylations with siletane 1.

Scheme 3.

Chemoselective aldehyde allylations using compound 1.

Scheme 4.

Chemoselective monoallylation of substrate 6 containing multiple electrophilic sites.

Scheme 5.

First attempts at the chemoselective allylation of aldehyde ketoacid 8.

Scheme 6.

Successful chemoselective ketone allylation of compound 8 by first alkoxy exchange followed by heating.

Scheme 7.

Selective cortisone and hydrocortisone monoallylation using siletane 13.