Asymmetric synthesis of β-hydroxy-α-amino phosphonic acid derivatives via organocatalytic direct aldol reaction of α-isothiocyanato phosphonates with aldehydes.
α-Isothiocyanato phosphonates are first used as nucleophiles to react with aldehydes for the asymmetric synthesis of β-hydroxy-α-amino phosphonic acid derivatives. The process is catalyzed by a quinine-derived thiourea via cascade aldol/cyclization reaction, affording a wide range of protected β-hydroxy-α-amino phosphonates containing adjacent quaternary-tertiary stereocenters in up to 93% yield, up to 81% ee, and >99:1 dr. This work represents the first example of α-isothiocyanato phosphonates serving as nucleophiles that are used in the catalytic asymmetric synthesis.
National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences , Chengdu 610041, China.
Wen-Yong
WY
Han
Jian-Qiang
JQ
Zhao
Zhi-Jun
ZJ
Wu
Xiao-Mei
XM
Zhang
Wei-Cheng
WC
Yuan
D000447:Aldehydes / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D017879:Isothiocyanates / Q000737:chemistry*; D015394:Molecular Structure; D010757:Phosphorous Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D013890:Thiourea / Q000737:chemistry*
D000447:Aldehydes; D000596:Amino Acids; D017879:Isothiocyanates; D010757:Phosphorous Acids; C570063:phosphonic acid; D013890:Thiourea