Samarium(II)-mediated spirocyclization onto an aromatic ring was achieved by the reaction of methyl 4-(4-oxoalkyl)benzoates with SmI(2) in the presence of i-PrOH and HMPA, yielding methyl 1-alkyl-1-hydroxyspiro[4.5]dec-6-ene-8-carboxylates in moderate to high yields. Utilizing this chemistry, spiro[3.5] and -[5.5] systems, and sterically congested spiro[4.5] systems, were easily synthesized. For the successful conversion, appropriate activation of the aromatic ring has proven to be extremely important: while an ester or amide functionality on the aromatic ring can promote the spirocyclization, a sulfonamide substituent causes ortho cyclization.

The first samarium(II)-mediated spirocyclisation onto an aromatic ring was achieved by the reaction of methyl 4-(4-oxoalkyl)benzoates with SmI2 in the presence of i-PrOH and HMPA, yielding methyl 1-alkyl-1-hydroxyspiro-[4.5]dec-6-ene-8-carboxylates in moderate to high yields.

Alkyl radicals generated by treatment of thiocarbamates of conformationally favorable 3-alkyl-3-arylpropan-1-ols with tris(trimethylsilyl)silane and AIBN efficiently undergo intramolecular ipso substitution of the methoxy group, yielding the corresponding cyclized products. In contrast, either conformationally favorable or flexible 1-arylalkan-3- or 4-ones easily cyclize into five- or six-membered condensed rings by treatment with SmI(2) via ketyl radical intermediates. The addition of HMPA as cosolvent dramatically changes the cyclization mode of the SmI(2)-induced reaction, and the para-cyclization products are exclusively formed. This "HMPA effect" can be rationalized by the strong chelating ability of HMPA with the samarium atom.

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Cyclohexane derivativesCyclohexane derivatives Q 0040 Samarium(II)-Promoted Radical Spirocyclization onto an Aromatic Ring. -A novel SmI 2 -mediated spirocyclization onto an aromatic ring is developed. Using this method stereoselective formation of spiro[3.5]nonenes, spiro[4.5]decenes, and spiro[5.5]undecenes is possible. The presence of an appropriate electron-withdrawing group such as an ester or amide group at para or ortho position is necessary for successful spirocyclization. -(OHNO, H.; OKUMURA, M.; MAEDA, S.-I.; IWASAKI, H.; WAKAYAMA, R.; TANAKA*, T.; J. Org. Chem. 68 (2003) 20, 7722-7732; Grad. Sch. Pharm. Sci.,