Towards Reaction Control: cis-Diastereoselective Reductive Dehydroxylation of 5-Alkyl-4-Benzyloxy-5-Hydroxy-2-Pyrrolidinones
- 化学化工－已发表论文 
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, beta-hydroxy-gamma-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 (3S,4S)-gamma-alkyl-beta-hydroxy-gamma-amino acids (6).