Asymmetric Reductive Amination in Organocatalysis and Biocatalysis

Abstract

This review summarizes the recent progress of organocatalytic and biocatalytic asymmetric reductive amination (ARA), a challenging but important topic for drug discovery and the pharmaceutical industry. At present, ARA can be divided into three categories: metal catalysis, organic catalysis, and biocatalysis. In the past decade, transition metal‐catalysed ARA has been well established. Organocatalytic ARA has emerged as a powerful alternative to metal‐catalysed ARA, the hydrogen sources used in organocatalytic ARA are usually Hantzsch esters, benzothiazolines, boranes, and hydrosilanes, which require Lewis base or phosphoric acid catalysts to activate them to give secondary chiral amines. It is worth mentioning that biocatalytic ARA has made remarkable progress in the last decade, amino acid dehydrogenases, amine dehydrogenases, opine dehydrogenases and imine reductases have been successfully used in ARA.

Chalcogen- and Halogen-Bond-Donating Cyanoborohydrides Provide Imine Hydrogenation

“…Although some of the σ-hole carriers − similarly with well-studied HB donorswere tested in the reaction of hydrogenation of the imine moiety by the Hantzsch esters (Scheme ), no examples were known for their applications involving simple inorganic reducing agents, such as hydrides, which might be explained by possible redox side reactions between the cationic σ-hole carrier and the reducing agent …”

“…In this work, we have applied the electrophilic properties of organic σ-hole donors to hydrogenation of an imino group by the cyanoborohydride anion, which is a required process in a series of reductive amination reactions leading to industrially important products. ,, Considering this, herein we report the synthesis and characterization of chalconium, iodonium, and iodoazolium cyanoborohydrides, as well as the kinetic study clearly representing a significant acceleration of the reduction of model imine in the presence of the XB and ChB donors compared to sodium and tetrabutylammonium cyanoborohydrides.…”

“…17−23 For ChB donors, recent publications unambiguously indicate that telluronium salts (R 3 Ch + X − , Ch = Te IV ) exhibit a significantly higher Lewis acidity compared to the tellurium(II) derivatives and lighter chalcogen(IV)-derived species, 24−32 whereas selenonium salts (Ch = Se IV ) have a higher 33,34 or comparable 35 activity than their sulfonium analogues (Ch = S IV ), which, in turn, exhibit a sufficient catalytic activity toward a series of model organic transformations. 34,36 Although some of the σ-hole carriers 36−43 �similarly with well-studied HB donors 44 �were tested in the reaction of hydrogenation of the imine moiety by the Hantzsch esters (Scheme 1), 45 no examples were known for their applications involving simple inorganic reducing agents, such as hydrides, which might be explained by possible redox side reactions between the cationic σ-hole carrier and the reducing agent. 46 In this work, we have applied the electrophilic properties of organic σ-hole donors to hydrogenation of an imino group by the cyanoborohydride anion, which is a required process in a series of reductive amination reactions leading to industrially important products.…”

Dynamic kinetic resolution of atropisomeric N-arylindoles via chiral N-triflyl phosphoramide catalyzed asymmetric reductive amination

“…8 Diverse centrally chiral acyclic and cyclic amines have been prepared in a highly enantioselective fashion by coupling aldehyde and ketone substrates with amines in the presence of a proper reducing agent. 9 Notably, 1,4-dihydropyridines (Hantzsch esters, HEs) have become the most popular biomimetic hydrogen sources. 10 However, in sharp contrast to the well-established organocatalyzed ARA for the construction of point chirality, its potential for the control of axial chirality lags behind and only four examples have been reported (Scheme 1).…”