PHOTOINDUCED MOLECULAR-TRANSFORMATIONS .155. GENERAL-SYNTHESIS OF MACROCYCLIC KETONES BASED ON A RING EXPANSION INVOLVING A SELECTIVE BETA-SCISSION OF ALKOXYL RADICALS, ITS APPLICATION TO A NEW SYNTHESIS OF (+/-)-ISOCARYOPHYLLENE AND (+/-)-CARYOPHYLLENE, AND A CONFORMATIONAL-ANALYSIS OF THE 2 SESQUITERPENES AND THE RADICAL INTERMEDIATE IN THE SYNTHESIS BY MM3 CALCULATIONS

The method used for a general synthesis of macrocyclic ketones based on a ring expansion involving a Selective beta-scission of alkoxyl radicals devised by Suginome and Yamada was extended and modified. Thus, cycloalkanones was transformed into the corresponding alpha-(omega-iodoalkyl)cycloalkanones by alkylation of the corresponding lithium enolates with either 1,3-diiodopropane or 1,4-diiodobutane. Treatment of these alpha-iodoalkyl cyclic ketones with samarium iodide gave bicyclic tertiary alcohols,The generation of the alkoxyl radicals from the bicyclic alcohols by irradiation of the corresponding hypoiodites generated with mercury(II) oxide-iodine-pyridine in benzene resulted in a selective beta-scission of their ring-junction bond to give high yields of macrocyclic ketones carrying an iodine which can be removed with tributyltin hydride. The method was then applied to new syntheses of (+/-)-isocaryophyllene and (+/-)-caryophyllene. Thus, omega-iodopropylation of ethyl 7,7-dimethyl-2-oxobicyclo [4.2.0]octane-3-carboxylate, followed by cyclization of the resulting alpha-(omega-iodoalkyl)cycloalkanone with samarium diiodide, gave cis-transoid-cis-ethyl 1-hydroxy-4,4-dimethyltricyclo [6.3.0.0(2,5)]undecane-8-carboxylate (69%). The ethoxycarbonyl group of this tricyclic alcohol was transformed into a methyl group by the standard method. Irradiation of a solution of the hypoiodite, prepared by the method mentioned above, with Pyrex-filtered light gave the corresponding cis-bicyclo[7.2.0]undecenone (15%), its exomethylene Isomer (<11%), and rearranged lactones (21%), all arising from cleavage of the ring-fusion bond of the generated alkoxyl radical. Basic isomerization of the cis-bicycloundecenone to its trans-isomer, followed by Wittig methylenation, gave (+/-)-isocaryophyllene. Sensitized photoisomerization of (+/-)-isocaryophyllene in hexane in the presence of methyl benzoate gave (+/-)-caryophyllene. The populations of conformers of caryophyllene, isocaryophyllene, and several related compounds, including a radical intermediate in the synthesis, were calculated by the empirical force-field method. The-relative populations of conformers comprising the radical intermediate generated by beta-scission of the ring-junction bond of the alkoxyl radicals derived from cis-transoid-cis-4,4,8-trimethyltricyclo [6.3.0.0(2,5)]undecan-1-ol mentioned above were correlated with the three products.