A More Comprehensive and Highly Practical Solution to Enantioselective Aldehyde Crotylation

Abstract

The enantioselective crotylation of aldehydes with 1,2-diaminochlorocrotylsilane reagents is effectively catalyzed by Sc(OTf)3. The one significant limitation on the utility of these reagents – substrate scope – has thus been addressed. The net result is the most comprehensive and highly practical method for enantioselective aldehyde crotylation yet advanced.

A “Methyl Extension” Strategy for Polyketide Natural Product Linker Site Validation and Its Application to Dictyostatin

“…26 Thus, silylformylation of 6-chlorohex-1-yne gave aldehyde 17 which was directly crotylated with ( S , S )- cis EZ-CrotylMix 20 to give 18 in 90% yield and 95% ee (Scheme 2). Tamao oxidation/ anti -diastereoselective tautomerization and protection of the aldehyde gave 19 in 66% yield over two steps.…”

Toward a more step-economical and scalable synthesis of spongistatin 1 to facilitate cancer drug development efforts

“…The resulting complex crotylsilane species is then reacted with an aldehyde partner in a Sc(OTf) 3 -catalyzed crotylsilylation reaction. 22 We applied the first two operations to 21 to generate complex crotylsilane 22 (Scheme 3). This was split in half and used in the Sc(OTf) 3 -catalyzed crotylation reactions of two different aldehydes which contain the necessary functionality for the installation of the C(16) methyl-bearing stereocenter and the C(17) ketone.…”

Complex fragment coupling by crotylation: a powerful tool for polyketide natural product synthesis

“…To that end, we considered an alternative approach based on a tandem Sc(OTf) 3 -catalyzed crotylsilylation 12 /Tamao oxidation/diastereoselective tautomerization 13 strategy that would join fragments such as 3 and 4 to produce the entire C(13)-C(17) array of functionality and stereochemistry in an efficient, stereoselective, and scalable way (Figure 1b). As exciting as this prospect seemed, however, its reduction to practice would be of little consequence unless equally efficient and scalable methods for the synthesis of 3 and 4 from simple prercursors could be developed.…”