Regiocontrolled benzannulation of diaryl(gem-dichlorocyclopropyl)methanols for the synthesis of unsymmetrically substituted alpha-arylnaphthalenes: application to total synthesis of natural lignan lactones.
[reaction: see text] An efficient synthesis of highly substituted alpha-arylnaphthalene analogues has been developed utilizing Lewis acid-promoted regiocontrolled benzannulation of aryl(aryl')-2,2-dichlorocyclopropylmethanols (aryl not equal 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 alpha-arylnaphthalenes in 40-91% yields with moderate to excellent regioselectivity (TiCl4 or SnCl4; >99/1-3/1, TBDMSOTf; >1/99-1/4). Thus, the alpha-aryl or alpha-aryl' moiety (accessory aryl group) was alternatively introduced to alpha-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).
Nishii
Yoshinori
Y
Department of Chemistry, Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano 386-8567, Japan. nishii@giptc.shinshu-u.ac.jp
Yoshida
Taichi
T
Asano
Hirofumi
H
Wakasugi
Kazunori
K
Morita
Jun-ichi
J
Aso
Yoshifumi
Y
Yoshida
Eri
E
Motoyoshiya
Jiro
J
Aoyama
Hiromu
H
Tanabe
Yoo
Y
D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008031:Lignin / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry*; D009281:Naphthalenes / Q000138:chemical synthesis*; D013057:Spectrum Analysis
D007783:Lactones; D009281:Naphthalenes; D008031:Lignin; D000432:Methanol