Synthetic and Mechanistic Studies on the Rhodium-Catalyzed Redox Isomerization of Cyclohexa-2,5-dienols

Abstract

We report the application of cyclohexa-2,5-dienols in a catalytic redox isomerization: a rhodium-catalyzed desymmetrization for the synthesis of γ,γ-disubstituted cyclohexenones. The reaction generates products which are useful intermediates in organic synthesis, and its functional group tolerance compares favorably to that of classical redox isomerizations. Through deuteration, crossover, and competition experiments, the mechanism was found to involve an intramolecular 1,3-hydride shift. The enantioselective version of the reaction was also studied.

Base-Catalyzed Stereospecific Isomerization of Electron-Deficient Allylic Alcohols and Ethers through Ion-Pairing

“…On the other hand, the R 2 and R 3 substituents can be varied to a larger extent; these may be electron-poor fluorinated groups, but importantly, also aryl groups with varied electron density, or even just hydrogen. It is important to highlight that TBD is able to isomerize not only fluorinated and electron poor alcohols, but also alcohols such as 1s – u , for which transition metal catalysts under basic conditions have been used. , …”

“…Allylic alcohols are readily accessible building blocks, and they are versatile synthons of carbonyl compounds via isomerization reactions. In the vast majority of instances, these are mediated by transition metal complexes. , Basic additives, in catalytic or stoichiometric amounts, are also needed in numerous transition metal-mediated isomerizations. The base is postulated to deprotonate the substrate alcohol, which can subsequently coordinate to the metal center forming transition metal alkoxides, key intermediates in the proposed catalytic cycles. ,,,, With chiral metal catalysts, the synthesis of chiral ketones , and aldehydes − with stereogenic centers at Cβ has been accomplished.…”

General, Simple, and Chemoselective Catalysts for the Isomerization of Allylic Alcohols: The Importance of the Halide Ligand

“…With a few exceptions, each catalyst isomerizes exclusively either primary or sec ‐allylic alcohols efficiently, and tend to follow distinct isomerization mechanisms: whereas sec‐ alcohols form enone intermediates, primary ones isomerize through migratory insertion/β‐hydride elimination sequences . For the latter, transition metal hydrides have given excellent results under mild conditions, enabling enantioselective isomerizations …”

Catalytic Asymmetric Isomerization of (Homo)Allylic Alcohols: Recent Advances and Challenges

“…In 2016, the Lautens group reported an enantioselective desymmetrizative redox isomerization of cyclohexa-2,5-dienols 33 catalyzed by a combination of [Rh(NBD) 2 ]BF 4 (5 mol %) and (R)-Tol-Garphos 34 (6 mol %), which delivered chiral γ,γ-disubstituted cyclohexanes 35 in 43-60 % ee (Scheme 13, eq 1). [25] Shortly after, Zhao and co-workers accomplished an enantioselective isomerization of bis-allylic alcohols 36 via desymmetrization, during the study of Rh-catalyzed enantioselective isomerization of secondary allylic alcohols, providing a facile way to access enantioenriched spirocyclic enones 38 bearing a γstereocenter (Scheme 13, eq 2). [23] In addition, the enantiospecific isomerization of optically pure secondary allylic alcohols has emerged as an alternative isomerization strategy for the synthesis of β-chiral ketones.…”

“…Apart from kinetic resolution and enantioconvergent isomerization, the secondary allylic alcohol isomerization involving desymmetrization strategy has recently received attention as well. In 2016, the Lautens group reported an enantioselective desymmetrizative redox isomerization of cyclohexa‐2,5‐dienols 33 catalyzed by a combination of [Rh(NBD) 2 ]BF 4 (5 mol %) and ( R )‐Tol‐Garphos 34 (6 mol %), which delivered chiral γ,γ‐disubstituted cyclohexanes 35 in 43–60 % ee (Scheme 13, eq 1) [25] . Shortly after, Zhao and co‐workers accomplished an enantioselective isomerization of bis‐allylic alcohols 36 via desymmetrization, during the study of Rh‐catalyzed enantioselective isomerization of secondary allylic alcohols, providing a facile way to access enantioenriched spirocyclic enones 38 bearing a γ‐stereocenter (Scheme 13, eq 2) [23] …”