Synthesis of nitrogen heterocycles via a-aminoalkyl radicals generated from a-silyl secondary amines under visible light irradiation†

Five-membered nitrogen heterocycles such as g-lactams and pyrroles are found in various natural products and pharmaceuticals. Construction of these skeletons in a simple and efficient manner is one of the most important topics in synthetic organic chemistry. In this context, the development of a novel synthetic approach for g-aminocarbonyl compounds composed of a secondary or primary amine moiety plays a pivotal role because a rapid 5-exocyclization between amine and carbonyl groups gives the corresponding nitrogen heterocycles. Construction of g-aminocarbonyl skeletons by the addition of a-aminoalkyl radicals derived from secondary amines to a,b-unsaturated carbonyl compounds under the photoinduced electron transfer conditions is a potentially useful strategy to access the corresponding nitrogen heterocycles. However, in these reaction systems, a large amount of N-alkylation products was usually observed due to the formation of aminyl radicals by oxidation of secondary amines (Scheme 1a) or direct thermal aza-Michael addition, where the desired g-aminocarbonyl compounds were obtained only in low yields. As a result, successful examples for synthetic utilization of a-aminoalkyl radicals under UV or visible light irradiation have been strictly limited to the use of tertiary amine derivatives. These results indicate that the generation and utilization of a-aminoalkyl radicals derived from secondary amines are quite difficult. Hence, we have envisaged the use of a-silylamines as substrates because dissociation of the a-C–Si bond of the radical cations occurs readily, which is considered to be suitable for selective formation of a-aminoalkyl radicals over aminyl radicals (Scheme 1b). In fact, we have recently succeeded in the synthetic utilization of a-aminoalkyl radicals generated from a-silyl tertiary amines in the presence of visible light-photoredox catalysts. In the course of our study, we have disclosed visible light-mediated synthetic utilization of a-aminoalkyl radicals generated from a-silyl secondary amines toward the addition to a,b-unsaturated carbonyl compounds, where the produced g-aminocarbonyl compounds are converted into the corresponding g-lactams and pyrroles in simple one-pot procedures. The preliminary results are described here. Initial investigations of one-pot synthesis of g-lactams were conducted using N-(trimethylsilylmethyl)aniline (1a) and diethyl benzylidenemalonate (2a) as substrates (Table 1). In the presence of 1 mol% of [4a][BF4], the reaction of 1a with 1.2 equiv. of 2a was carried out in N-methylpyrrolidone (NMP) under visible light Scheme 1 Photoreactions of secondary amines via (a) aminyl radicals and (b) a-aminoalkyl radicals.