Reductive Alkylation of Quinolines to N-Alkyl Tetrahydroquinolines Catalyzed by Arylboronic Acid

Abstract

A boronic acid catalyzed one-pot tandem reduction of quinolines to tetrahydroquinolines followed by reductive alkylation by the aldehyde has been demonstrated. This step-economcial synthesis of N-alkyl tetrahydroquinolines has been achieved directly from readily available quinolines, aldehydes, and Hantzsch ester under mild reaction conditions. The mechanistic study demonstrates the unique behavior of organoboron catalysts as both Lewis acids and hydrogen-bond donors.

Direct Dearomatization of Quinoline/Isoquinoline Ammonium Halides to Construct N‐Substituted Tetrahydroquinolines and Tetrahydroisoquinolines

“…Based on the previous literatures, [1–2,8d,10,13] we proposed a possible reaction mechanism (Scheme 5). The formation of tetrahydroquinoline 2 a can be reasonably carried out in two ways.…”

Emergent Organoboron Acid Catalysts

“…147 A combination of hydrogen bonding and Lewis acidity from arylboronic acids has also been applied to the reductive alkylation of quinolines with aldehydes, using a Hantzsch ester as the reductant (Scheme 44). 148 The boronic acid was proposed to activate both the quinoline and Hantzsch ester by hydrogen bonding to promote reduction to the tetrahydroquinoline, followed by Lewis acid activation of the aldehyde to promote reductive amination with the aldehyde, again highlighting the multiple modes of activation available to boronic acids. Recently, the Ishihara Group reported the enantioselective 1,4-addition of cycloalkanones to α,β-unsaturated carboxylic acids using the combination of a catalytic chiral secondary amine and an arylboronic acid (Scheme 45).…”