399044-21-4

Upstream product

• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 
• 106-95-6 allyl bromide 
• 19206-69-0 allyl diphenyl phosphate 

Downstream Products

• 197229-64-4 (S)-benzyl 2-allylpyrrolidine-1-carboxylate 
• 399044-23-6 (S)-Δ^6,7-indolizidin-5-one 

Relevant academic research and scientific papers

Asymmetric lithiation trapping of N -boc heterocycles at temperatures above -78°C

The asymmetric lithiation trapping of N-Boc heterocycles using s-BuLi/chiral diamines at temperatures up to -20°C is reported. Depending on the N-Boc heterocycle, lithiation is accomplished using s-BuLi and (-)-sparteine or the (+)-sparteine surrogate in the temperature range -50 to -20°C for short reaction times (2-20 min). Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered functionalized N-Boc heterocycles in 47-95% yield and 77:23-93:7 er. With N-Boc pyrrolidine, trapped products can be generated in ～90:10 er even at -20°C.

A new sparteine surrogate for asymmetric deprotonation of N-Boc pyrrolidine

(Chemical Equation Presented) The s-BuLi complex of a cyclohexane-derived diamine is as efficient as s-BuLi/(-)-sparteine for the asymmetric deprotonation of N-Boc pyrrolidine. This is the first example of high enantioselectivity using a non-sparteine-like diamine in such reactions. The ( S, S)-diamine is a useful (+)-sparteine surrogate and was utilized in short syntheses of (-)-indolizidine 167B and an intermediate for the synthesis of the CCK antagonist (+)-RP 66803.

Reactivity and Enantioselectivity in the Reactions of Scalemic Stereogenic α-(N-Carbamoyl)alkylcuprates

Stereogenic 2-(N-carbamoyl)pyrrolidinylcuprates prepared from scalemic (i.e., enantioenriched) N-Boc-2-lithiopyrrolidine and THF soluble CuCN·2LiCl react with vinyl iodides, vinyl triflates, β-iodo-α,β-enoates, propargyl mesylates, and allyl bromide to afford the substitution products with excellent enantioselectivity. Excellent enantiomeric ratios are obtained in the conjugate addition reactions with methyl vinyl ketone while low enantiomeric ratios can be achieved with acrylate esters using HMPA/TMSCl activation. Enantiomeric ratios vary with substrate substitution patterns and the observed enantioselectivities appear to be more a function of cuprate-electrophile reactivities than of the reaction type (e.g., substitution, conjugate addition). Low enantiomeric ratios are obtained with the α-(N-carbamoyl)benzylcuprates. The lithium-copper transmetalation and cuprate vinylation reactions proceed with retention of configuration.

Regio- and enantioselective control in the reactions of α-(N-Carbamoyl)alkylcuprates with allylic phosphates

α-(N-Carbamoyl)alkylcuprates (RCuCNLi or R2CuLi) react with allylic phosphates to afford homoallylic amines in good chemical yields. Regioselectivity is governed by steric factors in both the cuprate reagent and phosphate substrate and systems can be designed to give either the S N2′ or SN2 substitution product cleanly. Excellent enantioselectivities can be achieved with either a scalemic α-di[(N- carbamoyl)-alkyl]cuprate and an achiral phosphate or with a scalemic allylic phosphate and an achiral cuprate reagent.