Regioselectivity in the intramolecular carbon–hydrogen insertion in metal-catalysed decomposition of some cis-1-methyl-3-arylcyclohexyl diazomethyl ketones. A highly efficient homogeneous nickel catalyst for carbenoid insertion

Abstract

The comparative effectiveness of a variety of copper catalysts and a few transition-metal chelates [Ni(acac)₂, Pd(acac)₂, and Co(acac)₃] have been examined in the carbenoid decomposition of cis,cis-1,5-dimethyl-3-phenylcyclohexyl diazomethyl ketone (11), and cis-1 -methyl-3-phenyl- and p-methoxyphenyl-cyclohexyl diazomethyl ketones (9) and (10) with reference to the formation of the respective regioisomeric bicyclo-octanones through intramolecular carbon-hydrogen bond insertion at C-3 and C-5. The most thoroughly studied case was that of (11), which clearly revealed that intramolecular competition in this case with most of the metal-catalysts only marginally favours insertion.into Me–C–H bond leading to the bridged bicyclo[3.2.1]octanone (17) in comparison to that of Ph–C–H bond, resulting in the regioisomeric ketone (16). In the catalytic decomposition of (9) and (10) the intramolecular competition in each case strongly favours insertion into the tertiary benzylic bond leading mostly to (12) and (14) rather than the secondary ones, leading to the respective regioisomers (13) and (15). The homogeneous catalyst, Ni(acac)₂ has been found to be the most effective for these insertion reactions as well as the transformations of the octahydrophenanthrene diazo ketones (1a) and (1b) to the respective tetracyclic bridged-ketones (2a) and (2b). The key cyclohexanecarboxylic acids (3), (5), and (7)[for the diazo ketones (9), (10), and (11)], and the corresponding diastereoisomeric acids (4), (6), and (8) have been synthesised through a stereocontrolled route by lithium-ammonia and catalytic reduction of the corresponding benzylic γ-lactones (18), (19), and (20) respectively, and the conformational properties of their methyl esters (26)–(31) have been studied. A mechanism for the lithium–ammonia cleavage of the lactones with retention of configuration at the benzylic asymmetric centre has been advanced. Unambiguous synthesis of the bridged-ketones (12), (14), and (17) and the transformations of (12) and (14) to the respective cis-dicarboxylic acids (51) and (52) are reported.