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. 2023 Feb 7;28(4):1584.
doi: 10.3390/molecules28041584.

Enantioseparation of P-Stereogenic 1-Adamantyl Arylthiophosphonates and Their Stereospecific Transformation to 1-Adamantyl Aryl- H-phosphinates

Bence Varga  1 , Levente Buna  1 , Daniella Vincze  1 , Tamás Holczbauer  2 , Béla Mátravölgyi  1 , Elemér Fogassy  1 , György Keglevich  1 , Péter Bagi  1
Affiliations

Enantioseparation of P-Stereogenic 1-Adamantyl Arylthiophosphonates and Their Stereospecific Transformation to 1-Adamantyl Aryl- H-phosphinates

Bence Varga et al. Molecules. .

Abstract

A focused library of 1-adamantyl arylthiophosphonates was prepared in racemic form. An enantioseparation method was developed for P-stereogenic thiophosphonates using (S)-1-phenylethylamine as the resolving agent. Under optimized conditions, three out of the five arylthiophosphonates were prepared in enantiopure form (ee > 99%). The subsequent desulfurization of optically active arylthiophosphonates gave the corresponding H-phosphinates without significant erosion of enantiomeric purity (ee = 95-98%). Hence, this reaction sequence can be considered an alternative method for the preparation of 1-adamantyl aryl-H-phopshinates. The absolute configuration of the (S)-1-adamantyl phenylphosphonothioic acid was assigned using single-crystal XRD and it allowed the confirmation that the removal of the P = S group proceeds with retention of configuration. The organocatalytic applicability of (S)-1-adamantyl phenylphosphonothioic acid was also evaluated as a P-stereogenic Brønsted acid.

Keywords: H-phosphinate; P-stereogenic; enantioseparation; organocatalysis; thiophosphonate.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Preparation of racemic 1-adamantyl arylthiophosphonic acid derivatives (2).
Scheme 2
Scheme 2
Development of an enatioseparation for 1-adamantyl arylthiophosphonates (2).
Scheme 3
Scheme 3
Summary of the enantioseparation results of racemic 1-adamantyl arylthiophosphonates (2) using (S)-1-phenylethylamine ((S)-3a) under optimized conditions.
Figure 1
Figure 1
The crystallographically independent molecules in the asymmetric unit of the crystal without the atomic labelling. Hydrogens were omitted for clarity as well. Displacement ellipsoids are drawn at the 30% probability level for clarity.
Scheme 4
Scheme 4
Preparation of optically active (R)-1-adamantyl aryl-H-phosphinates ((R)-1a–c) by desulfurization of enantiopure (S)-1-adamantyl aryphosphonothioic acids ((S)-2a–c).
Scheme 5
Scheme 5
Asymmetric transfer hydrogenation of N-(4-methoxyphenyl)-1-phenylethanimine (4) and 2-methylquinoline (6) using (S)-2a as the organocatalyst.
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