Abstract
Dehydration and Rupe rearrangement of 2-(3,3-dimethylcyclohexyl)hex-3-yne-2,5-diol
(9) furnished as a 3% byproduct the
intense vetiver-like smelling 4,7,7-trimethyl-1-methylenespiro[4.5]decan-2-one
(11). Motivated by the commercial importance
of vetiver oil and the lack of synthetic substitutes as well as the
lack of insight into the structural requirements for vetiver odorants,
an efficient synthetic route to vetiver-like smelling compounds was
developed. It consists of Wittig-Horner-Emmons
reaction of diverse cycloalkanones with triethyl 2-phosphonopropionate,
subsequent Grignard reaction with in situ conversion to the trienolate, and
classical Nazarov cyclization of the resulting dienones. This route
not only leads to 11 in 61% yield
in the final Nazarov cyclization, but also to 16 analogs, which
provide insight into both, the Nazarov reaction and the structure-odor
relationship of vetiver odorants. Other vetiver-like smelling compounds
discovered include (1RS,4SR,5SR)-1,4,7,7-tetramethylspiro[4.5]decan-2-one (16), 4-methyl-1-methylenespiro[4.6]undecan-2-one
(30) and 4-methyl-1-methylenespiro[4.7]dodecan-2-one
(31).
Key words
cyclizations - khusimone - odor-structure correlation - spiro compounds - vetiver
