Experiments towards the synthesis of the ergot alkaloids and related structures. Part 2. New alkylations on α-carbon and nitrogen in α-amidoketones

Abstract

The alkylation of a number of α-amidoketones in the 3,4-dihydro-naphthalen-1(2H)-one and -acenaphthen-5(2aH)-one series, involving treatment with sodium hydride (1 or 2 mol equiv.) in dimethylformamide solution and subsequent reaction with alkyl halides, has been examined. Whilst the acetamido-derivatives furnished good yields of the C-alkyl products (6 and 8; R¹= Ac, R²= H, R³= alkyl), the formamido-ketones gave rise to a complex mixture on methylation, but with 2 mol equiv. of base, the CN-dimethylated ketones (6 and 8; R¹= CHO, R²= R³= Me) were obtained in essentially quantitative yield. In contrast, the keto-urethanes (14) and homologous oxamic esters (17) yielded the N-alkyloxazolinones [(15) and (16)] and N-alkyloxazinediones (19), respectively. All three groups of alkyl-derivatives could be converted in high yield (>95%) by acidic hydrolysis to the corresponding C- or N-alkyl- or CN-dialkyl-aminoketones. In addition the oxazinediones were found to be particularly sensitive to nucleophilic attack, a property which would appear to have useful synthetic potential.