RESUMEN
We developed an efficient method that enables selective photodimerization of 5-arylpenta-2,4-dienoic acids (i.e., vinylogous cinnamic acids). The use of 1,8-dihydroxynaphthalene as a template ensures proximity of the two reacting olefins so that irradiation of template-bound dienoic acids gives mono [2 + 2] cycloaddition products in good to excellent yields (up to 99%), as single regioisomers, and with high diastereoselectivities (dr = 3:1 to 13:1). The geometrical and stereochemical features of compounds 12a, 16a, and 22a were analyzed by X-ray crystallography.
RESUMEN
We have developed a catalytic aza-Nazarov reaction of N-acyliminium salts generated in situ from the reaction of a variety of cyclic and acyclic imines with α,ß-unsaturated acyl chlorides to afford substituted α-methylene-γ-lactam heterocycles. The reactions proceed effectively in the presence of catalytic (20 mol %) amounts of AgOTf as an anion exchange agent or hydrogen-bond donors such as squaramides and thioureas as anion-binding organocatalysts. The aza-Nazarov cyclization of 3,4-dihydroisoquinolines with α,ß-unsaturated acyl chlorides gives tricyclic lactam products 7 in up to 79% yield with full diastereocontrol (dr = >99:1). The use of acyclic imines in a similar catalytic aza-Nazarov reaction with 20 mol % of AgOTf results in the formation of α-methylene-γ-lactam heterocycles 19 in up to 76% yield and with good to high diastereoselectivities (4.3:1 to 16:1). We have demonstrated the scalability of the reaction with a gram-scale example. The relative stereochemistry of the α-methylene-γ-lactam products 19 has been determined via the single-crystal X-ray analysis of lactam 19l. In order to shed light on the details of the reaction mechanism, we have performed carefully designed mechanistic studies which consist of experiments on the effect of ß-silicon stabilization, the alkene geometry of the α,ß-unsaturated acyl chloride reactants, and adventitious water on the success of the catalytic aza-Nazarov reaction.
RESUMEN
We developed a general method for the selective photochemical homo- and heterodimerization of cinnamic acid derivatives with the use of commercially available 1,8-dihydroxynaphthalene as a covalent template. A variety of symmetrical and unsymmetrical ß-truxinic acids were obtained in high yields and as single diastereomers. The use of a template not only provides the alignment of the two olefins with suitable proximity (<4.2 Å) but also allows the heterodimerization of two different cinnamic acids, leading to unsymmetrical ß-truxinic acid products.