Stereoselective Access to Fully Substituted Aldehyde‐Derived Silyl Enol Ethers by Iridium‐Catalyzed Alkene Isomerization

Abstract

An in situ generated cationic Ir‐catalyst isomerizes simple allylic silyl ethers into valuable, fully substituted aldehyde‐derived silyl enol ethers. Importantly, by judicious choice of substrate, either of the two possible stereoisomers of a given enolate derivative is accessible with complete stereoselectivity. One‐pot isomerization‐aldol and isomerization‐allylation processes illustrate the synthetic utility of this method.

Stereoselective Sc(OTf)3‐Catalyzed Aldol Reactions of Disubstituted Silyl Enol Ethers of Aldehydes with Acetals

“…The two stereoisomers Eand Z-6 were readily synthesized by using the complementary procedures that we have previously developed for the preparation of disubstituted enolates of aldehydes (Scheme 3). [9,10] The excellent stereoselectivity in both cases shows that these two methods can also be successfully applied to enolates of different substitution patterns.…”

“…Importantly, the complementary diastereomer is accessible as well, with similar diastereoselectivity and yield, by simply inverting the stereochemistry of the starting enol silyl ether (3 b provides 5 b in 78 % yield and 96:04 diastereomeric ratio, Scheme 2). The relative stereochemistry of 5 b has been determined by comparison with a previously reported product [10] and all other configurations were assigned by analogy. This transformation is stereoselective, as the two starting silyl enol ethers 3 a and 3 b are of E:Z ratios of 02:98 and 96:04 and provide the two aldol products with 95:05 and 96:04 diastereomeric ratios, respectively.…”

“…In this context, we have recently reported two complementary approaches toward stereodefined disubstituted aldehyde-derived silyl enol ethers 3 by using an allyl-Brook rearrangement of allylic silyl carbinols (Scheme 1, path a) [9] or through iridium-catalyzed alkene isomerization of allyl silyl ethers (Scheme 1, path b). [10] In both cases, either geometrical isomer of a given enolate was accessible as a single regio-and stereoisomer from readily available starting materials.…”

Iron‐Catalyzed Positional and Geometrical Isomerization of Alkenes

“…For decades, precious metal‐based catalysts such as Ru, [29–41] Rh, [42–48] Pd, [49–57] Ir, [58–71] Pt, [72–74] and Mo, [75,76] have been at the forehead of metal‐catalyzed alkene isomerization to address the challenges and selectivity issues and to enrich the reaction applications pertaining to scope and synthetic usefulness. However, the low abundance, high cost and high toxicity of these metals have stimulated the exploration of earth‐abundant first‐row late transition metals as sustainable alternatives that could additionally feature distinct and complementary reactivity behaviors thanks to a large set of redox and spin states [77] .…”