Synthesis of an Enantiomerically Pure Inherently Chiral Calix[4]Arene Phosphonic Acid and Its Evaluation as an Organocatalyst

Abstract

A facile method for the preparation of enantiomerically pure inherently chiral calix[4]arene phosphonic acid (cR,pR)-7 in four steps starting from the readily available and previously synthesized (cS)-enantiomer of calix[4]arene acetic acid 1 or its methyl ester 2 was developed. The first tests of this unique calixarene Brönsted acid with inherent chirality in organocatalysis of the aza-Diels-Alder reaction of imines with Danishefsky's diene and epoxide ring opening by benzoic acid were performed. The calixarene phosphonic acid (cR,pR)-7 shows good catalytic activities but with low enantioselectivities in these reactions.

Confinement Effects in Catalysis Using Well-Defined Materials and Cages

“…In the case where water was present, the diastereoselectivities (65:35) were moderate whereas the enantioselectivities were high (up to 92%). In addition, several other studies in the field of asymmetric catalysis by enantiopure calix[n]arenes have been recently reported (Li et al, 2011, 2017; Karpus et al, 2018; Sahin et al, 2018).…”

Recent applications of chiral calixarenes in asymmetric catalysis

“…Manoury et al have very recently reported facile synthesis of an enantiomerically pure inherently chiral calix[4]arene phosphonic acid ( cR,pR )- 121 from the readily available ( cS )-enantiomer of calix[4]arene acetic acid 119 or its methyl ester 120 in four steps ( Scheme 39 ) [ 73 ]. The organocatalytic properties of this inherently chiral calixarene Brønsted acid was firstly examined in the aza-Diels–Alder reaction of imines bearing electron-withdrawing or electron-donating substituents 122 with Danishefsky’s diene ( 123 , Scheme 40 ).…”

Chiral phosphorus-containing calixarenes

“…The calixarenphosphates 6 have been converted into free acids and their diastereomeric salts with chiral L-phenylethylamine were separated by the achiral HPLC method 11 . Optically pure calixarene phosphonous acid 16 was synthesized in accordance with Scheme 4 13 . As the building blocks we used optically pure chiral calixarene acetic acid 10 or its methyl ester 11 14 The optically pure calixarene phosphonous acid 16 catalyses the asymmetrical Diels-Alder cyclisation of imines with Danishefsky diene 13 .…”

“…Optically pure calixarene phosphonous acid 16 was synthesized in accordance with Scheme 4 13 . As the building blocks we used optically pure chiral calixarene acetic acid 10 or its methyl ester 11 14 The optically pure calixarene phosphonous acid 16 catalyses the asymmetrical Diels-Alder cyclisation of imines with Danishefsky diene 13 . Unfortunately enantiomeric excess of the reaction is low.…”