| This dissertation describes the scope and limitations of the isomerization of epoxides to carbonyl compounds with a homogeneous transition metal catalyst. The most effective catalytic system that was employed for the selective isomerization of activated and unactivated epoxides comprised 5 mol% Pd(OAc){dollar}sb2{dollar} and 15 mol% PBu{dollar}sb3{dollar} in either refluxing tert-butyl alcohol or toluene. Unactivated epoxides such as long-chain mono-alkyl-substituted epoxides containing a methyl, primary hydroxyl, {dollar}alpha,beta{dollar}-unsaturated ester, nitrile, terminal olefinic or an additional epoxy group were selectively isomerized to produce methyl ketones in 85-96% yield. Activated epoxides, such as aryl-substituted epoxides bearing multiple methyl substituents, reacted via exclusive cleavage of the benzylic C-O bond to form benzylic aldehydes or ketones in excellent yields. The isomerization of aryl-substituted epoxides demonstrated good tolerance of reactive functional groups, such as terminal alkenyl, primary alcohol, nitrile, ester and ketone. Both Pd(OAc){dollar}sb2{dollar} and PBu{dollar}sb3{dollar} were required in order to generate an active catalyst for the isomerization reaction. Other low-valent transition metal complexes such as Ni(0)- and Rh(I)-tertiary phosphine complexes were also investigated, but were found to be less efficient, as were the Pd(0) complexes Pd{dollar}sb2{dollar}(dba){dollar}sb3{dollar} and Pd(PPh{dollar}sb3)sb4.{dollar} The Pd(0) catalyst isomerizes epoxides in a wide range of solvents, with different polarities.; The Pd(0)-catalyzed isomerization of aryl-substituted epoxides to benzylic carbonyl compounds can be considered as a two-step protocol for the homologation of an aryl aldehyde or ketone to a higher carbonyl compound. We can also compare our methodology to conventional Lewis acid catalyzed epoxide isomerizations, which are prone to unselective reactions with certain substrates. Under our reaction conditions no allylic alcohols or products arising from alkyl migration were formed; instead, only hydride migration with formation of carbonyl compounds was observed. We were also able to control the reactivity of electronically dissimilar epoxy groups within the same molecule by altering the catalyst composition. Another attractive feature of this methodology is the two-step protocol of alkene epoxidation with m-chloroperbenzoic acid, followed by Pd-catalyzed isomerization, which shows greater chemoselectivity in the oxidation of substrates containing both terminal and conjugated carbon-carbon double bonds. In contrast, the Wacker oxidation, which employs Pd(II) to catalyze alkenes to carbonyl compounds, is less selective, and has the tendency to oxidize both terminal and conjugated C=C.; Kinetic and deuterium labeling studies of the isomerization of aryl-substituted epoxides with Pd(OAc){dollar}sb2{dollar}/PBu{dollar}sb3{dollar} support a three-step mechanism (following the in situ- generation of Pd(0)): (1) turnover-limiting S{dollar}sb{lcub}rm N{rcub}{dollar}2-type oxidative addition of Pd(0) to the epoxide, which cleaves one C-O bond, (2) rapid {dollar}beta{dollar}-hydride elimination to form a Pd(II)-hydrido-enolate complex, and (3) rapid reductive elimination, which forms the carbonyl compound and regenerates the catalyst. |
