Cyclobutyl annelation

Related to the pyridine studies are the results of base-catalyzed hydrogen exchange in cyclobutabenzene derivatives, which suggest that cyclobutyl annelation increases both the kinetic and thermodynamic acidity at the a-position. The most significant study is the thermodynamic deprotonation/carboxylation reaction of cyclobutabenzene with amyl sodium/COj, in which only the a-carboxy isomer is formed (Figure 6). This is consistent with the value for the a-proton being several p units lower than that for the P-proton in cyclobutabenzene (38). 

Cyclobutyl annelation. Trost and Keeley have used this reagent for a double cyclobutyl annelation in a stereoselective synthesis of grandisol (8), a constituent of the boU weevil sex pheromone. The starting material (1) is obtained by the conjugate addition of thiophenol to methacrolein. This is converted into the cyclobutanone (2) by reaction with 1-lithiocyclopropyl... 

CYCLOBUTYL ANNELATION 1-Lithiocyclopropylphenyl sulfide. CYCLODEHYDRATION Magnesium methyl carbonate. Pyridine hydrochloride. CYCLODEHYDROGENATION Sodium aluminum chloride. 

Grota, J., Domke, I., Stoll, I., Schroder, T., Mattay, J., Schmidtmann, M., Bogge, H., and Muller, A. (2005) Synthesis, fragmentation, and rearrangement reactions of annelated cyclobutyl-carbinols. Synthesis, 2321-2326. 

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