Highly enantioselective synthesis of beta-aminophosphinates with two stereogenic atoms and their conversion into optically pure ethyl beta-amino-H-phosphinates.
beta-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 beta-aminophosphinates (>95 % ee; see scheme). Subsequent removal of the protecting groups through pivotal metal-catalyzed thiophenolysis leads to optically pure ethyl beta-amino-H-phosphinates.The first highly stereoselective synthesis of beta-aminophosphinates has been realized by the nucleophilic attack of an anion generated from ethyl (1,1-diethoxyethyl)methylphosphinate and nBuLi on (S)-N-(tert-butanesulfinyl)imines at -78 degrees C. Subsequent removal of the protecting groups through pivotal metal-catalyzed thiophenolysis leads to optically pure ethyl beta-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 alpha-aminophosphinates and beta-aminophosphinates. On the other hand, the Cram rules have been successfully applied to rationalize the highly enantioselective formation of (R(C))-alpha-aminophosphinates and (R(C))-beta-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.
Zhang
Dehui
D
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Feng-lin Road, Shanghai, China.
Yuan
Chengye
C
D002384:Catalysis; D018360:Crystallography, X-Ray; D007097:Imines / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D007097:Imines; D010721:Phosphinic Acids