10.1021/ja000520u
The research investigates the factors influencing stereoselectivity in the coupling reaction between a chiral C2-symmetric nitroxide, trans-2,5-dimethyl-2,5-diphenylpyrrolidin-1-oxyl (DPPO), and various stabilized secondary prochiral radicals. The study aims to understand how steric and electronic effects, as well as reaction conditions such as temperature, solvent polarity, and viscosity, impact the stereoselectivity of the coupling reactions. Key chemicals used include DPPO as the chiral nitroxide, and prochiral radicals generated from substrates like tert-butyl propionate, methyl propionate, and benzyl hydrazines through methods involving CuCl2 oxidation, Mn(salen) catalysis, and lead dioxide oxidation. The researchers found that higher stereoselectivity was achieved in reactions carried out at 0 °C compared to those started at -78 °C and warmed to room temperature. Solvent viscosity significantly affected stereoselectivity, with higher selectivity observed in less viscous solvents like diethyl ether (dr = 5.2:1) compared to more viscous solvents like ethylene glycol (dr = 2.1:1). Solvent polarity had a less pronounced effect, with relatively constant diastereoselectivity across solvents of varying polarity. Ab initio calculations predicted a C-O-N angle of attack greater than 110° at a carbon-oxygen bond-forming distance of approximately 2.2 ?, though no transition state was identified. The study concludes that while steric effects play a significant role in stereoselectivity, electronic effects and reaction conditions also contribute to the overall outcome of the coupling reactions.
10.1016/S0040-4039(00)87168-3
The research presents a novel synthetic method for creating 3-amino-2-alkenoates, which are valuable intermediates for synthesizing various heterocycles like pyridines, pyrimidines, indoles, and isothiazoles. These compounds also exhibit anti-inflammatory properties in some N-aroyl derivatives. The study explores the use of magnesium enolates of t-butyl (or ethyl) acetate and t-butyl propionate, which react with nitriles to produce 3-amino-2-alkenoates with Z configuration. The researchers initially attempted using lithium enolate of t-butyl acetate but found it ineffective due to the instability of the primary adduct and the inability of the lithium ion to incorporate the nitrile group. Instead, they successfully employed magnesium enolate derived from diisopropylamine and ethylmagnesium bromide, achieving efficient yields of the desired compounds. The procedure was applicable to various nitriles, although those with relatively acidic o-hydrogen atoms resulted in lower yields. Protected acetaldehyde cyanohydrins also yielded good results. The products were characterized by GLC and 1H-NMR spectroscopy, confirming their structures and configurations.
