Studies towards the N-acylative kinetic resolution of NOBIN

Abstract

An investigation into the N-acylation of atropisomeric anilines 8 and 2, which are related to NOBIN (1), catalysed by small molecule chiral pyridine-based nucleophilic catalysts is described. The first organocatalytic kinetic resolution (KR) of an atropisomeric aniline is described.

Kinetic Resolution of Axially Chiral 2‐Amino‐1,1′‐Biaryls by Phase‐Transfer‐Catalyzed N‐Allylation

“…[1] In particular, the kinetic resolution of amino compounds has become a topic of great scientific interest in recent years (Scheme 1). [3] In contrast, examples of catalytic kinetic resolutions of axially chiral amino compounds of type 1 (Scheme 1 b) are quite limited, [5][6][7] despite the high synthetic utility of these compounds as chiral building blocks for the synthesis of chiral ligands, catalysts, and biologically active compounds ( Figure 1). [3] In contrast, examples of catalytic kinetic resolutions of axially chiral amino compounds of type 1 (Scheme 1 b) are quite limited, [5][6][7] despite the high synthetic utility of these compounds as chiral building blocks for the synthesis of chiral ligands, catalysts, and biologically active compounds ( Figure 1).…”

“…[2][3][4] Various kinds of racemic primary and secondary amines have been submitted to non-enzymatic kinetic resolutions through N-acylation promoted by chiral nucleophilic catalysts to produce optically active amines (Schemes 1 a,c). [8,9] Although nucleophilic-catalystpromoted N-acylation has also been applied to the kinetic resolution of 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives, the acylations showed only modest selectivities (s = 1.4-4.4, Scheme 1 c) [5] and the catalytic kinetic resolution of these axially chiral compounds still remains a challenging task. [8,9] Although nucleophilic-catalystpromoted N-acylation has also been applied to the kinetic resolution of 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives, the acylations showed only modest selectivities (s = 1.4-4.4, Scheme 1 c) [5] and the catalytic kinetic resolution of these axially chiral compounds still remains a challenging task.…”

Kinetic Resolution of Axially Chiral 2‐Nitrovinyl Biaryls Catalyzed by a Bifunctional Thiophosphinamide

“…[3] In addition, axially chiral molecules also serve as a privileged scaffold for chiral auxiliaries, ligands, and catalysts in asymmetric synthesis. [5] These can be divided into four major categories: 1) Enantioselective biaryl coupling of two aryl counterparts; [6] 2) asymmetric functionalization of prochiral biaryls; [7] 3) dynamic kinetic resolution [8] or kinetic resolution of racemic biaryls; [9] 4) chiral aryl axis formation via central-to-axial chirality transfer strategy. [5] These can be divided into four major categories: 1) Enantioselective biaryl coupling of two aryl counterparts; [6] 2) asymmetric functionalization of prochiral biaryls; [7] 3) dynamic kinetic resolution [8] or kinetic resolution of racemic biaryls; [9] 4) chiral aryl axis formation via central-to-axial chirality transfer strategy.…”

Stereoelectronic Basis for the Kinetic Resolution of N‐Heterocycles with Chiral Acylating Reagents

“…These reagents also suffered from a greater degree of epimerization during the amine resolutions, resulting in a greater proportion of diastereomeric amide products. The poor results from these examples may be an underlying reason for the slow development of chiral reagents for amine resolution, which despite some notable successes from Fu, [9] Krasnov, [10] Mioskowski, [11] Seidel, [12] Spivey, [13] and others, [14] has not kept pace with developments in other areas of asymmetric synthesis.…”