Catalysis of Enantioselective Strecker Reaction in the Synthesis of D‐Homophenylalanine Using Recyclable, Chiral, Macrocyclic Mn^III–Salen Complexes

Abstract

A convenient approach to the asymmetric Strecker reaction was established by synthesizing chiral, mono‐ and dinuclear, macrocyclic MnIII–salen complexes possessing achiral and chiral linkers (trigol, piperazine, and diethyl tartarate). This group of macrocyclic complexes has emerged as improved metal‐based catalysts for the enantioselective Strecker reaction of aldimines, giving high enantioselectivity (up to 99 %) for a wide range of substrates. The macrocylic complex 6 a with trigol linker works very well with TMSCN (trimethylsilyl cyanide) as a source of cyanide, using 4‐phenyl pyridine N‐oxide (4‐PPyNO) as a co‐catalyst in toluene at −40 °C. However, the macrocyclic complex 6 b with diethyl tartarate as a linker affected excellent chiral induction for both aromatic and aliphatic imines with a safer cyanide source (ethyl cyanoformate) in toluene at −20 °C in the presence of N,N‐diisopropylimine as a co‐catalyst. Complexes 6 a and 6 b used in the present study were recoverable and recyclable (five times) with retention of their performance at gram level. The kinetic study with complex 6 a for the enantioselective Strecker reaction of N‐benzyl benzylimine revealed a first‐order dependence on catalyst, substrate, and TMSCN concentration. This protocol with catalyst 6 b was further extended for the synthesis of D‐homophenyl alanine, an important analogue in factor Xa inhibitors.

Diethyl Tartrate Linked Chiral Macrocyclic Manganese(III)–Salen Complex for Enantioselective Epoxidation of Olefins and Oxidative Kinetic Resolution of Racemic Secondary Alcohols

“…For the sake of comparison, we used our previously developed catalysts for the epoxidation reaction [17][18][19]24] (Scheme 2). For the sake of comparison, we used our previously developed catalysts for the epoxidation reaction [17][18][19]24] (Scheme 2).…”

“…All chromenes [28,29] and 3-tert-butyl-5-(chloromethyl)-2-hydroxybenzaldehyde [30] were synthesized according to reported procedures. [17][18][19]24] The absolute configurations of chiral 1-phenylethanol were determined by comparing the sign of optical rotation (obtained from PDR-ALP) with the standard. [31] 1 H and 13 C NMR spectra were recorded on Bruker 200 or 500 MHz spectrometers at ambient temperature.…”

“…These studies mainly addressed the issues of improving yield and catalyst recyclability to make the process more acceptable for industry. [17][18][19] The linkers used to build the macrocycle were diethyl tartrate (DET), homopiperazine, 1,1'-binaphthol (BINOL), and 1,3-benzenedimethanol, which were placed across the 5,5'-positions of the salen moiety. Di-and polymeric Mn III -salen complexes have been reported as recyclable enantioselective epoxidation catalysts by linking through the 5,5'- [13][14][15] and 3,3'-positions [16] of salen units by using various types of chiral and nonchiral linkers.…”

Chiral Salen Complexes for Asymmetric Heterogeneous Catalysis: Recent Examples for Recycling and Cooperativity

“…For instance, corresponding Mn‐salen complexes were engaged in the cyanation reaction of aldimines and optimal results were obtained with the Mn‐complex possessing the triethylene glycol spacer for the transformation of various aromatic and aliphatic imines (up to 95 % yield and 99 % ee). Accordingly, and starting from the same ligand, a chiral dimeric macrocyclic V‐salen complex was used in the same reaction with potassium‐ or trimethylsilyl cyanide (15 examples, up to 95 % yield and 99 % ee) .…”

Metal complexes of amino acids and peptides

“…89 Coppercatalyzed oxidation of amino acid derivatives as models for enzymatic oxidation of amino acids have also been studied. 91 Production of catalitically active metal complexes of amino acids and various derivatives has a permanent interest because of many reasons. In a recent work, a chiral, macrocyclic Mn(III)-salen complex has been successfully used for the synthesis of D-homophenyl alanine.…”