Towards Reaction Control: cis‐Diastereoselective Reductive Dehydroxylation of 5‐Alkyl‐4‐Benzyloxy‐5‐Hydroxy‐2‐Pyrrolidinones

Abstract

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, b-hydroxy-g-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 NaBHA C H T U N G T R E N N U N G (OAc) 3 . cis-5-Alkyl-4benzyloxy-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)-g-alkyl-bhydroxy-g-amino acids (6).

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

“…Compound (8 S ,8a S )- 5 would be of value for the synthesis of other pumiliotoxins as well. The highly diastereoselective trans -addition of a methylmagnesium iodide to keto-lactam 10 provides a new example of achieving the desired diastereoselection simply by the chair-conformation control [52–53]. …”