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Highly Enantioselective Synthesis of β‐Aminophosphinates with Two Stereogenic Atoms and Their Conversion into Optically Pure Ethyl β‐Amino‐ H ‐phosphinates
Author(s) -
Zhang Dehui,
Yuan Chengye
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200802248
Subject(s) - diastereomer , stereocenter , enantioselective synthesis , chemistry , chirality (physics) , stereoselectivity , stereochemistry , optically active , nucleophile , amino acid , nucleophilic addition , stereoisomerism , catalysis , organic chemistry , physics , biochemistry , nambu–jona lasinio model , chiral symmetry breaking , quantum mechanics , quark
β‐Amino acid analogues : The nucleophilic addition of ethyl (diethoxyethyl)methylphosphinate to a variety of ( S )‐( tert ‐butanesulfinyl)imines leads to the isolation of two enantioenriched β‐aminophosphinates (>95 % ee ; see scheme). Subsequent removal of the protecting groups through pivotal metal‐catalyzed thiophenolysis leads to optically pure ethyl β‐amino‐ H ‐phosphinates.The first highly stereoselective synthesis of β‐aminophosphinates has been realized by the nucleophilic attack of an anion generated from ethyl (1,1‐diethoxyethyl)methylphosphinate and n BuLi on ( S )‐ N ‐( tert ‐butanesulfinyl)imines at −78 °C. Subsequent removal of the protecting groups through pivotal metal‐catalyzed thiophenolysis leads to optically pure ethyl β‐amino‐ H ‐phosphinates. During this process, a pair of diastereoisomers with different configurations on the phosphorus atom can be obtained. Until now, Ellman N ‐( tert ‐butanesulfinyl)imines have demonstrated excellent chirality‐induced activity in the syntheses of both α‐aminophosphinates and β‐aminophosphinates. On the other hand, the Cram rules have been successfully applied to rationalize the highly enantioselective formation of ( R C )‐α‐aminophosphinates and ( R C )‐β‐aminophosphinates, whereas the phenomenon that the two pairs of diastereoisomers could both be efficiently isolated is tentatively discussed based on X‐ray crystallographic and 1 H NMR spectroscopic analysis.