Carvone hydrochloride in the synthesis of thiazole-containing C11–C21-block of epithilones gem-dimethylcyclopropane analogs

Abstract

Starting with R-(-)-carvone hydrochloride a synthesis was developed of the key chiral block for the epothilones gem-dimethylcyclopropane analog.

Rac-2′,3a,6,6,6′,6′-Hexamethyl-3a,3b,6,7-tetra-hydrospiro-[benzo[2,3]cyclopropa[1,2-c]pyrazole-1,1′-cyclo-hepta[2,4]diene]

“…A recent synthesis program in our laboratory concerned the conversion of eucarvone 1, that was prepared by literature methods [2,3], into its deoxygenated cycloheptatriene counterpart 2 (Scheme 1). To perform this transformation, we opted to convert eucarvone into its tosylhydrazone derivative (3), which upon treatment with base was expected to undergo a Bamford-Stevens reaction [4,5].…”

“…To perform this transformation, we opted to convert eucarvone into its tosylhydrazone derivative (3), which upon treatment with base was expected to undergo a Bamford-Stevens reaction [4,5].…”

“…Eucarvone 1 was prepared from carvone by literature known methods [2,3] and isolated as a colorless oil. The synthesis of tosylhydrazone 3 from eucarvone 1 was accomplished as follows: tosyl hydrazine (1.1 mmol, 205 mg) and one drop of acetic acid were added to a solution of eucarvone (1, 1 mmol, 150 mg) in MeCN (0.5 M).…”