α-Alkylation of carbonyl compounds using a Brønsted base is a fundamental carbon-carbon bond-forming reaction for constructing basic molecular skeletons. Among these transformations, the alkylation using alkenes as electrophiles (hydroalkylation) is more desirable than traditional alkylation with alkyl halides due to its superior atom economy (i.e., no salt waste). However, while activated alkenes such as α,β-unsaturated carbonyl compounds are commonly used, nonactivated alkenes like 1-hexene remain challenging due to their low electrophilicity. Despite this limitation, nonactivated alkenes are attractive electrophiles, offering access to a diverse range of alkyl substituents and functional groups. Here, we report efficient α-alkylation of active methylene and methine compounds with nonactivated alkenes. This method employs an organophotocatalyst (4CzIPN or its derivative) and lithium thiophenoxide (LiSPh) as a multifunctional catalyst system, enabling Lewis acid/Brønsted base/hydrogen atom transfer (HAT) catalysis under blue LED irradiation. The reactions proceed smoothly under ambient conditions with low catalyst loadings, affording the desired alkylated products in high yields using only a slight excess of the carbonyl compound and without by-product formation. This represents a practical and atom-economical alkylation strategy. Furthermore, we found that magnesium thiophenoxide (Mg(SPh)2) exhibits higher catalytic activity than LiSPh, allowing for further reduction in catalyst loading. In addition, a metal Lewis acid/amine/PhSH system proved effective for the alkylation of active methine compounds, and even a metal-free simple amine/PhSH system was effective for the alkylation of malononitrile.
Yasuhiro Yamashita (Mon,) studied this question.
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