Samarium diiodide promoted generation and asymmetric hydroxyalkylation of N,O-diprotected (3S)-3-pyrrolidinol 2-carbanions.
The N,O-diprotected chiral nonracemic 2-pyridyl 3-pyrrolidinol-2-yl sulfide 5a undergoes efficient SmI(2) mediated reduction to give the N,O-diprotected 3-pyrrolidinol 2-carbanion intermediate D, which reacted under Barbier-type conditions with ketones and aldehydes to afford the protected N-alpha-hydroxyalkyl-3-pyrrolidines 10b-h with excellent diastereoselectivity at the newly formed chiral center in the pyrrolidine ring. Application of the present method led to the formal asymmetric syntheses of (2R,3S)-2-hydroxymethyl-3-pyrrolidinol (2) and (2S,3S)-3-hydroxyproline (12). [reaction: see text]
Zheng
Xiao
X
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. China.
Feng
Chen-Guo
CG
Ye
Jian-Liang
JL
Huang
Pei-Qiang
PQ
D000838:Anions; D002219:Carbamates; D006900:Hydroxylation; D007454:Iodides; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011759:Pyrrolidines / Q000138:chemical synthesis*; D012493:Samarium
D000838:Anions; D002219:Carbamates; D007454:Iodides; D011759:Pyrrolidines; D012493:Samarium; C409809:samarium diiodide; C059692:phenylcarbamic acid