α-Monohalogenated imines have proved as invaluable intermediates in the synthesis of nitrogen-containing heterocycles and β-haloamines due to the presence of two contiguous electrophilic positions.<br/>The main strategies proposed for the generation of halogenates ketimines include electrophilic halogenation of imines/enamines or condensation of α-halogenated ketones with amines.<br/>Both procedures present serious disadvantages. The electrophilic halogenation conveys low regioselectivity and formation of polyhalogenated products. On the other hand, condensation of α-halogenated ketones is very sensitive to steric hindrance, provides low selectivity, and commonly requires the use of high excess of amines. Furthermore, purification and isolation of α-monohalogenatedketimines is challenging due to their facile hydrolysis and has not yet been achieved. Thus, the use of this valuable intermediates in the presence of undesirable substances is unavoidable and may complicate following transformations.<br/>Here we present a straightforward methodology for the preparation of α-chloromethylketimines in high yields with total selectivity and full atom economy making unnecessary any purification step. The new synthetic method comprises the gold (I)-catalyzed hydroamination reaction of chloroalkynes. Complete conversions into the desired products have been observed with aromatic amines and both aliphatic and aromatic chloroalkynes with catalyst loads as low as 0.3 mol %. This powerful proposed route is also applicable for substrates presenting electron donating or withdrawing groups or high steric hindrance.

Straightforward route to α-chloromethylketimines through gold(I) catalysis

ACS Spring Meeting 2021

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