218601-58-2

Upstream product

• 19009-39-3 N,N-diisopropylcarbamoyl chloride 
• 122-97-4 3-Phenyl-1-propanol 
• 79-22-1 methyl chloroformate 
• 218601-55-9 3-phenylpropyl N,N-diisopropylcarbamate 
• 1435902-80-9 (1S)-1-(p-tolylsulfinyl)-3-phenylpropyl N,N-diisopropylcarbamate 

Relevant academic research and scientific papers

Preparation and reactions of enantiomerically pure α-functionalized grignard reagents

A strategy for the generation of enantiomerically pure α- functionalized chiral Grignard reagents is presented. The approach involves the synthesis of α-alkoxy and α-amino sulfoxides in ≥99:1 dr and ≥99:1 er via asymmetric deprotonation (s-BuLi/chiral diamine) and trapping with Andersen's sulfinate (menthol derived). Subsequent sulfoxide → Mg exchange (room temperature, 1 min) and electrophilic trapping delivers a range of enantiomerically pure α-alkoxy and α-amino substituted products. Using this approach, either enantiomer of products can be accessed in 99:1 er from asymmetric deprotonation protocols without the use of (-)-sparteine as the chiral ligand. Two additional discoveries are noteworthy: (i) for the deprotonation and trapping with Andersen's sulfinate, there is a lack of stereospecificity at sulfur due to attack of a lithiated intermediate onto the α-alkoxy and α-amino sulfoxides as they form, and (ii) the α-alkoxy-substituted Grignard reagent is configurationally stable at room temperature for 30 min.

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.