Atroposelective Transfer Hydrogenation of Biaryl Aminals via Dynamic Kinetic Resolution. Synthesis of Axially Chiral Diamines

Abstract

An efficient dynamic kinetic resolution (DKR) approach for the synthesis of axially chiral diamines has been developed on the basis of a ruthenium-catalyzed enantioselective transfer hydrogenation. The strategy relies on the configurational instability of cyclic biaryl aminal precursors in equilibrium with their amino-imine open forms, as supported by DFT calculations. This protocol features a broad substrate scope of aliphatic amines and biaryl scaffolds and proceeds under very mild conditions, allowing the preparation of BINAM homologues in good to high yields and nearly perfect enantioselectivities (up to 99% ee).

Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage

“…A similar approach has been developed for the DKR of biaryl aminals to synthesize axially chiral diamines. 284 In 2021, Wang and co-workers reported the atroposelective dynamic kinetic resolution of biaryl aldehydes to form axially chiral biaryl amino acid esters using N-heterocyclic carbene (NHC) catalysts (Figure 78). 285 The authors hypothesized that the NHC could act as a chiral nucleophile to preferentially esterify with one enantiomer of the biaryl aldehyde, which is rapidly racemizing through the hemiaminal intermediate proposed in their previous work.…”

“…Then the iminium ion is enantioselectively reduced to form the configurationally stable product amine and Ir-complex 77.V . A similar approach has been developed for the DKR of biaryl aminals to synthesize axially chiral diamines …”

Cinchona Alkaloid Catalyzed Dynamic Kinetic Resolution of Biaryl Aldehydes via Asymmetric Decarboxylative Transamination

“…Dynamic kinetic resolution (DKR) 10 of bridged biaryl lactones, uncovered by the Bringmann group 11 and then expanded by the groups of Yamada, 12 Wang, 13 Zhang, 14 and Fu 15 has proven to be an efficient tool for the enantioselective synthesis of chiral biaryls. Later on, expanded bridged biaryl mixed hemiaminals were reported by Akiyama 16 and then used by our group 17 and the Hornillos group 6d to accomplish the assembly of chiral biaryls. Inspired by these achievements, we report herein the quinine-catalyzed atropo­enantioselective synthesis of axially chiral biaryls via a decarboxylative transamination and DKR strategy (Scheme 1c ).…”

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.…”