Prev. Article Next Article Table of Contents

Article

Use of Aromatic Radical-Anions in the Absence of THF. Tandem Formation and Cyclization of Benzyllithiums Derived from the Attack of Homo- and Bishomoallyllithiums on α-Methylstyrenes: Two-Pot Synthesis of Cuparene¹

Supporting Info

Theodore Cohen,* Thanapong Kreethadumrongdat, Xiaojun Liu, and Vithalanand Kulkarni

Contribution from the Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

J. Am. Chem. Soc., 2001, 123 (15), pp 3478–3483

DOI: 10.1021/ja004353+

Publication Date (Web): March 23, 2001

To whom correspondence should be addressed: cohen@pitt.edu; 412-624-8220.

Abstract

When a homo- or bishomoallyllithium, generated by reductive lithiation of the corresponding phenyl thioether by the radical anion lithium 1-(dimethylamino)naphthalenide (LDMAN), is added to α-methylstyrene, a tandem addition/cyclization to a phenyl-substituted five- or six-membered-ring occurs. The yields are compromised by polymerization of the α-methylstyrene, a process favored by tetrahydrofuran (THF), the solvent used to generate lithium aromatic radical anions. Thus, a new method of generating LDMAN (unsuccessful for other common radical anions) in the absence of THF has been developed. The radical anion can be generated and the reductive lithiation performed in dimethyl ether at −70 °C. After the addition of diethyl ether or other solvent, and evaporation of the dimethyl ether in vacuo, the α-methylstyrene is added and the solution is warmed to −30 °C. When the unsaturated alkyllithium is primary, no adduct forms in THF due to polymerization of the α-methylstyrene, but moderate yields are attained in a solvent containing mainly hexanes. It was also found that the cyclized organolithiums, which would have become protonated in the presence of THF, can be captured by an electrophile, even at ambient temperature. A two-pot synthesis, the most efficient reported, of the sesquiterpene (±)-cuparene in 46% yield, using this technology is reported.

View: Full Text HTML | Hi-Res PDF