Competitive Enantiodifferentiating Anti-Markovnikov Photoaddition of Water and Methanol to 1,1-Diphenylpropene Using A Sensitizing Cyclodextrin Host

Abstract

UV-vis, circular dichroism (CD), fluorescence, and NMR spectral studies on the self-inclusion behavior of a newly synthesized sensitizing host, 6-(5-cyanonaphthyl-1-carboamido)-6-deoxy-beta-cyclodextrin (1), showed that the appended naphthalene moiety of 1 perches laterally on the cyclodextrin rim in aqueous methanol but is shallowly included and somewhat tilted in its own cavity in water. UV-vis and CD spectral examinations of the complexation of guest substrate 1,1-diphenylpropene (DPP) with host 1 revealed the formation of a stoichiometric 1:1 complex of DPP with 1. The naphthyl fluorescence of 1 was efficiently quenched by the addition of DPP in aqueous solutions of low methanol contents (<or=25%) but was less efficiently quenched in more hydrophobic solvents (>or=50% methanol), where the fluorophore is not included in the cavity and allows the external attack of DPP to form an exciplex in the bulk solution. Upon irradiation in aqueous solutions of different methanol contents, competitive photoaddition of water and methanol to DPP occurred to give chiral water adduct 3 and methanol adduct 4, favoring the latter product by a factor of 2.5 due to the higher nucleophilicity of methanol. The enantiomeric excess (ee) values of the photoadducts were generally low in highly methanolic solutions, but was greatly improved by increasing the water content to reach 18% ee for 3 and 13% ee for 4 in 10% methanol solution at -10 degrees C. Interestingly, the ee of methanol adduct 4 was consistently lower than that of water adduct 3 particularly in water-rich solvents, revealing that the product's ee is not a simple thermodynamic function of the enantioface-selectivity upon complexation of DPP by chiral host 1 but also kinetically controlled by the subsequent photoinduced enantioface-differentiating nucleophilic attack of water and methanol to radical cationic DPP generated photochemically. Compatible with this mechanism, the compensation plot of the differential activation enthalpy versus entropy, which were obtained from the van't Hoff analysis of the temperature-dependent ee's obtained in aqueous solutions of varying methanol contents, gave an excellent straight line for water adduct 3 but an unprecedented bent plot for methanol adduct 4, indicating a switching of the mechanism in between 35 and 50% methanol solution. By using high pressure, low temperature, and/or added salt, the ee of water adduct 3 was further enhanced to 24-26%.