Enantioselective Catalysis of an Anionic Oxy‐Cope Rearrangement Enabled by Synergistic Ion Binding

Abstract

Charge-accelerated rearrangements present interesting challenges to enantioselective catalysis, due in large part to the competing requirements for maximizing reactivity (ion-pair separation) and stereochemical communication. Herein, we describe application of a synergistic ion-binding strategy to catalyze the anionic oxy-Cope rearrangement of a symmetric bis-styrenyl allyl alcohol in up to 75 : 25 e.r.Structure-reactivity-selectivity relationship studies, including linear free-energy-relationship analyses, with bifunctional urea catalysts indicate that H-bonding and cation-binding interactions act cooperatively to promote the chemo-and enantioselective [3,3]-rearrangement. Implications for catalyst designs applicable to other transformations involving oxyanionic intermediates are discussed.

DyKAT by DiCat: Stereoconvergent Dienamine-Catalyzed Claisen Rearrangements

“…Preliminary control experiments indicated that the Claisen rearrangement was not being promoted by a dienol­(ate) species (entry 2), suggesting that catalyst 3b may be acting via the formation of a dienamine intermediate. While the use of BzOH was intended to enhance amine catalyst activity or possibly accelerate the Claisen rearrangement via hydrogen bonding, , nontrivial quantities (∼10% yield) of allyl benzoate were observed as a byproduct. Thus, about half of the BzOH was being deactivated and, in the process, presumably, the starting material was destroyed.…”

“…Given the ubiquity of enamine and iminium catalysis, it is surprising that sigmatropic rearrangements are not more firmly established in this catalytic repertoire. Organocatalytic asymmetric [3,3]-sigmatropic rearrangements using N -heterocyclic carbene, noncovalent hydrogen bonding/Brønsted acidic, and other organocatalysts have emerged. By contrast, there is one isolated example of an asymmetric [3,3]-sigmatropic rearrangement proceeding via a catalytically generated iminium ion intermediate, in which the product is generated in 54% yield and 47% ee .…”

Recent Advances in Catalytic [3,3]-Sigmatropic Rearrangements

“…Asymmetric Cope rearrangement was demonstrated with the chiral catalyst 172, affording aldehyde 171 in 54% yield with 47% ee (Scheme 35b). In 2020, Jacobsen's group reported an urea-catalyzed enantiosective anionic oxy-Cope rearrangement (Scheme 36) [78]. The authors attempted to elucidate the reaction mechanism by testing various reaction conditions using structurally different catalysts and additives.…”

Bi(OAc)3/Chiral Phosphoric Acid-Catalyzed Enantioselective 1,2- and Formal 1,4-Allylation Reaction of β,γ-Unsaturated α-Ketoesters

“…The most stable precursor ( M1-1 ) and chairlike mode gave the most stable transition state. In addition, the overlap between the high-lying oxyanion nonbonding (n O ) orbital and the adjacent σ* CC orbital (or the lowest-lying antibonding molecular orbital, ψ 4 π ) weakens the C–C bond and promotes the process of [3,3]-rearrangement . Thus, the rate of transformation from 1,2-allylation products to 1,4-allylation products remarkably increases when the OH group is deprotonated.…”