913642-88-3

Upstream product

• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 
• 100-52-7 benzaldehyde 
• 24424-99-5 di-tert-butyl dicarbonate 

Relevant academic research and scientific papers

Mechanistic interrogation of the asymmetric lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine

A fundamental mechanistic study of the s-BuLi/chiral diamine-mediated lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine is reported. We show that lithiated thiopivalamides are configurationally unstable at -78 °C. Reaction then proceeds via a dynamic resolution of diastereomeric lithiated intermediates and this accounts for the variable sense and degree of asymmetric induction observed compared to N-Boc heterocycles.

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.

Investigation of bispidines as the stoichiometric ligand in the two-ligand catalytic asymmetric deprotonation of N-Boc pyrrolidine

A range of achiral bispidines have been synthesized and evaluated as the stoichiometric ligand in the two-ligand catalytic asymmetric deprotonation of N-Boc pyrrolidine. ARKAT USA, Inc.

Asymmetric deprotonation using s -BuLi or i -PrLi and chiral diamines in THF: The diamine matters

The solution structures of [6Li]-i-PrLi complexed to (-)-sparteine and the (+)-sparteine surrogate in Et2O-d10 and THF-d8 at -80 °C have been determined using 6Li and 13C NMR spectroscopy. In Et2O, i-PrLi/(-)-sparteine is a solvent-complexed heterodimer, whereas i-PrLi/(+)-sparteine surrogate is a head-to-tail homodimer. In THF, there was no complexation of (-)-sparteine to i-PrLi until ≥3.0 equiv (-)-sparteine and with 6.0 equiv (-)-sparteine, a monomer was characterized. In contrast, the (+)-sparteine surrogate readily complexed to i-PrLi in THF, and with 1.0 equiv (+)-sparteine surrogate, complete formation of a monomer was observed. The NMR spectroscopic study suggested that it should be possible to carry out highly enantioselective asymmetric deprotonation reactions using i-PrLi or s-BuLi/(+)-sparteine surrogate in THF. Hence, three different asymmetric deprotonation reactions (lithiation-trapping of N-Boc pyrrolidine, an O-alkyl carbamate, and a phosphine borane) were investigated; it was shown that reactions with (-)-sparteine in THF proceeded with low enantioselectivity, whereas the corresponding reactions with the (+)-sparteine surrogate occurred with high enantioselectivity. These are the first examples of highly enantioselective asymmetric deprotonation reactions using organolithium/diamine complexes in THF.

Catalytic asymmetric synthesis of piperidines from pyrrolidine: Concisesynthesis of L-733,060

Catalytic asymmetric deprotonation-aldehyde trapping-ring expansion from a 5- to a 6-ring delivers a concise route to each stereoisomer of -hydroxy piperidines starting from W-Boc pyrrolidine. The methodology is utilized in a 5-step catalytic asymmetric synthesis of the neorokinin-1 receptor antagonist, (+)-L-733,060.