Regiocontrolled Benzannulation of Diaryl(gem-dichlorocyclopropyl)methanols for the Synthesis of Unsymmetrically Substituted α-Arylnaphthalenes:  Application to Total Synthesis of Natural Lignan Lactones

An efficient synthesis of highly substituted α-arylnaphthalene analogues has been developed utilizing Lewis acid-promoted regiocontrolled benzannulation of aryl(aryl‘)-2,2-dichlorocyclopropylmethanols (aryl ≠ aryl‘; abbreviated as AACMs). Both AACM diastereomers were easily prepared via highly stereoselective addition (>95/5) of ArLi to gem-dichlorocyclopropropyl aryl‘ ketones. The choice of Lewis acids determined the cyclization regioselectivity of the present benzannulation. TiCl4 and SnCl4 used the chelation pathway, whereas silyl triflates used a nonchelation pathway to give unsymmetrically substituted regioisomeric α-arylnaphthalenes in 40−91% yields with moderate to excellent regioselectivity (TiCl4 or SnCl4; >99/1−3/1, TBDMSOTf; >1/99−1/4). Thus, the α-aryl or α-aryl‘ moiety (accessory aryl group) was alternatively introduced to α-arylnaphthalenes by choosing either the order of the reaction sequences or the appropriate catalyst. Application of the present method to the total synthesis for unsymmetrically substituted natural lignan lactones, justicidin B, retrojusticidin B, dehydrodesoxypodophyllotoxin, and a related analogue, 5‘-methoxyretrochinensin, was demonstrated. Lignan retrolactones (retrojusticidin B and 5‘-methoxyretrochinensin) were synthesized by the conventional lactonization of the diol precursor, whereas a novel Bu2SnO-mediated monoacylation method was applied to the synthesis of normal lignan lactones (justicidin B and dehydrodesoxypodophyllotoxin).