Amine Synthesis by A-Alkylation

Several mild and efficient alcohol alkylation (alkoxylation) methods are known, including the classic Williamson reaction, alkyl halide and silver oxide in combination, and alkyl triflate and 2,6-di-terf-butyl-4-methylpyridine. However, for sterically hindered or optically labile alcohols, alternative powerful and mild methodology is required. 

Diem et al. reported a mild alkoxylation reaction using trialkyloxonium tetrafluoroborate (Meerwein s salt) [7]. In this reaction. Proton Sponge (1) was found to be an effective base, as well as Hiinig s base (diisopropylethylamine) (Table 8.1). The reaction of (R)-(+)-l-phenylethyl alcohol with Meerwein s trimethyloxonium tetrafluoroborate (2.1 equiv.) and Proton Sponge (1) (2.1 equiv.) in dichloromethane at room temperature gave methyl ether in 69% yield without loss of optical purity (Table 8.1, run 1). (5)-(—)-2-Methyl-l-butanol was also methylated in 57% yield (run 3). 

The drastic effect of molecular sieves of 4 A (4 A MS) was reported by Ireland etal. [11], Although, methylation of alcohol with Meerwein s salt and Proton Sponge (1) in combination took place much faster than in the alternative protocol, the reaction stopped at about 50% conversion in the case of alcohol, and decomposition of the spiroketal moiety was observed 

Kanemasa et al. reported an asymmetric conjugate addition reaction of thiol to A-crotonyl oxazolidinone in the presence of Ni(II)-DBFOX/Ph catalyst [20] (Table 8.2). In this reaction. Proton Sponge (1) is indispensable for high enantioselectivity, and thioether was obtained in 84-99% yield with 91-94% ee. 

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