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Towards Reaction Control: cis ‐Diastereoselective Reductive Dehydroxylation of 5‐Alkyl‐4‐Benzyloxy‐5‐Hydroxy‐2‐Pyrrolidinones
Author(s) -
Wang YuHuang,
Ou Wei,
Xie Linfeng,
Ye JianLiang,
Huang PeiQiang
Publication year - 2012
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201200113
Subject(s) - pyrrolidinones , chemistry , alkyl , diastereomer , rational design , stereochemistry , organic chemistry , combinatorial chemistry , genetics , biology
A chemo‐, regio‐, and stereoselectively controlled reaction is highly desirable, yet challenging in organic synthesis. Diversely substituted cis and trans isomers of 2‐alkyl‐3‐pyrrolidinols, 5‐alkyl‐4‐hydroxy‐2‐pyrrolidinones, β‐hydroxy‐γ‐amino acids, and their higher homologues are key structural units found in numerous drugs, drug candidates, and bioactive natural products. Previously, we established a flexible approach to trans ‐5‐alkyl‐4‐benzyloxy‐2‐pyrrolidinones 14 and trans ‐6‐alkyl‐5‐benzyloxy‐2‐piperidinones 15 . Herein, we report a direct, flexible, moisture insensitive, and highly diastereoselective approach to the corresponding cis diastereomers 16 . This stereocontrolled method is based on the MsOH‐mediated (Ms=methane sulfonyl) reductive dehydroxylation of hemiaminal 12 with NaBH(OAc) 3 . cis ‐5‐Alkyl‐4‐benzyloxy‐2‐pyrrolidinones 16 are useful building blocks for the syntheses of natural products such as (+)‐preussin ( 4 ) and streptopyrrolidine ( 5 ) as well as (3 S ,4 S )‐γ‐alkyl‐β‐hydroxy‐γ‐amino acids ( 6 ).