1218989-40-2

Upstream product

• 1218989-23-1 (S,E)-N-(4-chloro-1-(4-bromophenyl)butylidene)-2-methylpropane-2-sulfinamide 
• 1218989-39-9 C₁₄H₂₁BrClNOS 
• 4559-96-0 1-(4-bromophenyl)-4-chlorobutan-1-one 

Downstream Products

• 1189155-63-2 (R)-2-(4-bromophenyl)-pyrrolidine 

Relevant academic research and scientific papers

PROCESS FOR SYNTHESIS OF 2-SUBSTITUTED PYRROLIDINES AND PIPERADINES

The present invention provides a highly efficient, versatile one-step process for asymmetric synthesis of either diastereomer of 2-substituted pyrrolidines from a single starting material with excellent yields and high diastereoselectivety. Also provided is a method for the asymmetric synthesis of both diastereomers of 2-substituted piperidines with good yields and excellent diastereoselectivety. Diasteroselectivity is controlled effectively by choice of reducing agent.

A facile asymmetric synthesis of either enantiomer of 2-substituted pyrrolidines

Chemical Reaction Reprentation A new and general method for asymmetric synthesis of either enantiomer of 2-substituted pyrrolidines from a single starting material is described. Reductive cyclization of (Ss)-γ-chloro-N- tertbutanesulfinyl ketimines with LiBHEt3 in THF at -78 to 23 °C afforded (Ss,R)-N-tert-buta.nemnnyl-2-substituted pyrrolidines in excellent yields (88-98%) and with high diastereoselectivity (99:1). The diastereoselectivity is controlled effectively by the choice of reducing agent. Thus, the corresponding epimers of (3 to DIBAL-H/LiHMDS. Deprotection of N-fe/ f-butanesulfinyl-2-substituted pyrrolidines using 4 N HCl in dioxane and MeOH gave the corresponding enantiomers of 2-substituted pyrrolidines in quantative yield. This method was found to be effective for a variety of substrates including aromatic, heteroaromatic, and aliphatic substituents. Extension of this methodology to the formation of 2-substituted piperidines is also illustrated. Reductive cyclization of (5s)-3 in THF at -78 to 23 °C or DIBAL-H/LiHMDS in toluene at -78 to 0 °C afforded the (Ss,R?)-N-tert-butanesulfinyl-2-substituted piperidines in excellent yield (98%) and with high diastereoselectivity (99:1) or (Ss,S)-.N-tert-butanesulfmyl- 2substituted piperidines in good yield (98%) and with high diastereoselectivity (1:99), respectively.