The Silyloxy-Cope Rearrangement of Syn-Aldol Products: Evolution of a Powerful Synthetic Strategy

Abstract

Enantiomerically pure 1,5-hexadienes incoporated into a silylated aldol structure undergo rapid, clean, high-yielding and highly stereoselective Cope rearrangements. The 7-oxo-2-enimides thus obtained are formally the products of a γ-1,4-selective addition of a metal dienolate to an α,β-unsaturated aldehyde − a transformation which current methodology can not accomplish directly and stereoselectively. They have proved to be very useful synthetic intermediates en route to highly substituted oxygen and nitrogen heterocycles, functionalized cyclohexanes, and 1,3,5,…-polyol chains.

Reactions of tris(dimethylsilyl)methane and polymers containing si—h groups with various hydroxy compounds under aerobic and mild conditions

“…The alcoholysis requires a catalyst because alcohols are not generally sufficiently nucleophilic to attack hydrosilanes. Strongly nucleophilic or electrophilic catalysts can be used [2], and a limited number of transition metal complexes [4][5][6][7][8][9][10]. It has been found that chloroplatinic acid, even in minute amounts, is an extremely potent catalyst, but few examples have been reported in the literature [11].…”

An unprecedented stereoselective [2+2] cycloreversion of cyclobutanones

“…Since rate accelerations were achieved by the introduction of silyloxy groups into Cope systems, 17 an attempt to also facilitate the cycloreversion started from silylether 7 which was subjected to thermal conditions up to 300 1C. However, only the Cope rearrangement product 8 was isolated after in situ hydrolysis (Scheme 2).…”

Dramatic Effect of γ-Heteroatom Dienolate Substituents on Counterion Assisted Asymmetric Anionic Amino-Cope Reaction Cascades

“…Our observations are particularly noteworthy when contrasted with the corresponding oxy-anion version, which when substituted with electron withdrawing groups such as esters and amides in the 4-position succumbs to the unwanted retro-aldol pathway . In the context of realizing asymmetric rearrangement goals with such substrates, Schneider, − Nakai, Black, and Davies have demonstrated that protection of the troublesome 3-hydroxyl with a silyl or benzoate group allows the oxy-Cope rearrangement to proceed albeit at very high temperatures in addition to two steps (protection/deprotection) being added to the overall synthetic sequence.…”