Asymmetric Autoamplification in the Oxidative Kinetic Resolution of Secondary Benzylic Alcohols Catalyzed by Manganese Complexes

Abstract

Herein, chiral Mn–aminopyridine complexes have been shown to catalyze the oxidation of alkylarenes to enantiomerically enriched 1‐arylalkanols with hydrogen peroxide. The observed enantiomeric excess values result from the direct enantioselective benzylic C−H hydroxylation, accompanied by stereoconvergent oxidative kinetic resolution of the resulting alcohol. Testing several (S,S)‐bipyrrolidine derived Mn complexes has revealed a novel catalyst (6) that exhibits the best kinetic resolution in the series (krel up to 8.8), along with sufficient reactivity and efficiency (>1000 catalytic turnovers). The mechanistic study of the Mn‐mediated alcohol oxidation witnesses electrophilic active species (ρ=−1.2), with rate‐limiting H abstraction (kH/kD=2.2), followed by oxygen rebound and dehydration of the resulting gem‐diol to form the ketone. Intriguingly, while for the resolution of the relatively bulky 1,2‐diphenylethanol, krel is virtually constant throughout the reaction, for less bulky alcohols, krel increases with increasing conversion, in line with the rising optical purity of the 1‐arylalkanol. The latter participates in the oxidation as an auxiliary ligand, assisting the chiral recognition. This effect is related to the previously described asymmetric autocatalysis and asymmetric autoinduction, but is not identical with either of those, with the differences being discussed. To unambiguously identify this effect, the term asymmetric autoamplification (chiral autoamplification) is proposed.

Chiral Manganese Aminopyridine Complexes: the Versatile Catalysts of Chemo‐ and Stereoselective Oxidations with H2O2

“…In effect, the formation of two diastereomeric active sites, exhibiting different alcohol stereoselectivity, resulted in monotonous increase of the observed k rel . This dynamic non‐linear effect (NLE) is related to the previously described asymmetric autocatalysis and asymmetric autoinduction phenomena, yet not identical with either of those . To identify this effect, the term asymmetric autoamplification ( chiral autoamplification ) has been proposed.…”

“…Very recently, the first Mn‐aminopyridine catalyzed asymmetric C−H hydroxylation has been reported. In particular, complex 21 has been found to conduct the C−H hydroxylation of ethylbenzene and p ‐ethyltoluene in 41 and 50 % ee , respectively, in the presence of EHA, and in 76 and 86 % ee , respectively, in the presence of N ‐ Boc ‐( L )‐proline, performing up to>500 turnovers (Scheme ) . In the presence of acetic acid, the oxidation was accompanied by stereoconvergent oxidative kinetic resolution of the resulting benzylic alcohols.…”

“… Enantioselective C−H hydroxylation of ethylbenzenes and oxidative kinetic resolution of 1‐arylalkanols in the presence of Mn aminopyridine catalyst ,…”

“…The kinetic resolution reaction (Scheme ) was studied in detail . In the presence of EHA, there was no resolution in 1‐Ph‐ethanol oxidation, while in the absence of any acid, the chiral recognition was the best, the k rel approaching 7.2 and 8.8 for the resolution of 1‐phenylethanol and 1‐( p ‐methylphenyl)ethanol, respectively (Scheme ).…”

“…The last decade has given birth to a new generation of manganese based catalysts, relying on aminopyridine ligands, that have exhibited excellent chemo‐ and stereoselectivity in the asymmetric epoxidation of olefins with “green” H 2 O 2 , and 10 1 ‐10 2 times higher efficiencies than Mn‐salen catalysts ,,. Moreover, it has been found that Mn aminopyridine complexes are capable of catalyzing the selective oxidation of non‐activated aliphatic and benzylic C‐H groups with H 2 O 2 ; very recently, the possibility to conduct these transformations in enantioselective fashion has been demonstrated ,. Reactions of this type hold a potential for the paradigm shift in the syntheses of complex organic molecules, taking into consideration the introduction of oxidized functionality at late steps of multistep syntheses …”