η⁶‐Arene CH−O Interaction Directed Dynamic Kinetic Resolution – Asymmetric Transfer Hydrogenation (DKR‐ATH) of α‐Keto/enol‐Lactams

Abstract

A dynamic kinetic resolution – asymmetric transfer hydrogenation (DKR‐ATH) methodology of α‐keto/enol‐lactams was developed. We also propose a possible catalytic mechanism evolving a transition state stabilized by η6‐arene CH−O interaction. The efficient approach can be applied to a wide range of substrates including non‐aryl ones which would be difficult to prepare by other asymmetric reduction methods.

Catalytic Stereoconvergent Synthesis of Homochiral β-CF3, β-SCF3, and β-OCF3 Benzylic Alcohols

“…Dynamic kinetic resolution based on Noyori–Ikariya transfer hydrogenation (DKR-ATH) seemed like a fitting synthetic strategy for addressing the challenging simultaneous control of both chiral centers of the target compound class. − DKR-ATH is a robust method for stereoconvergent access to enantiomerically pure secondary alcohols with multiple contiguous chiral centers starting from the readily available racemic α-substituted ketones, − including fluorinated examples. − This approach to β-CF 3 alcohols would involve in situ epimerization of α-CF 3 ketones via an enol or enolate-anion intermediate. Specifically, α-CF 3 enolates have been associated with decomposition due to fluoride elimination to furnish the corresponding unstable difluoroenone. − This was foreseen as the major obstacle toward an efficient DKR-ATH-based catalytic asymmetric synthesis of β-CF 3 alcohols.…”

Dynamic Kinetic Resolution of β-Substituted α-Diketones via Asymmetric Transfer Hydrogenation

“…In this context, a large number of racemic ketones such as α-substituted cyclic ketones, acyclic ketones bearing α-electron-withdrawing groups (EWGs), α-ketoesters bearing β-labile stereocenters, and so forth, have been exploited to undergo efficient ATH-DKR to afford a variety of enantioenriched secondary alcohols with adjacent stereocenters . The great value of such processes has been witnessed in the synthesis of various pharmaceuticals, fine chemicals, agrochemicals, flavors, and so forth, by a plethora of companies . Considering the extreme importance of AH/ATH-mediated DKR, the exploration of a new substrate type that could undergo different DKR modes and release distinct types of enantiopure products is highly desirable since such a kind of project has the potential to open a new window to update the known understanding of ATH and thus further promote the practical value of the field.…”

Hydrogen-Bonding Ability of Noyori–Ikariya Catalysts Enables Stereoselective Access to CF3-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution

“…Efficient DKR relies on a fast dynamic interconversion of the starting material’s enantiomers and on a highly enantio-discriminating asymmetric transformation. , Noyori–Ikariya type ruthenium catalysts for asymmetric transfer hydrogenation (ATH), for example C1 – C8 (Figure a), − were used in efficient DKR of several classes of complex ketones. − Traditionally, the origin of enantioselectivity for the reduction of ketones with this type of catalyst has been associated with the CH/π interaction between an electron-deficient η 6 -arene ligand and π electrons of the ketone substrate . Configuration at the α-stereocenter during DKR-ATH was deemed to be controlled by the steric repulsion (Figure b), − although this assertion was rarely supported by computational analysis. , …”