Exploration of donor/acceptor carbenoids in a multitude of rhodium(II) catalyzed asymmetric reactions
Ventura, Dominic Louis
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Chiral dirhodium(II) catalysis has been shown to exhibit a wide range of asymmetric reactions. As will be demonstrated in this thesis, a wide variety of transformations can be achieved by this chemistry. The first part of this dissertation will discuss the subtle differences that can occur when utilizing very similar aromatic heterocycles in reactions with donor-acceptor carbenoids. By altering the heteroatom, opposite asymmetric induction can be achieved in biscyclopropanation of the heterocycle in good yields and high selectivity (up to 93% yield, >94% de and up to 96% ee). In addition, a number of other types of carbenoid reactions can be observed with these heterocycles, including C-H insertion. With the study extended to aromatic carbocycles, in some cases similar reactivity to that of the aromatic heterocycles was displayed. Rhodium(II) complexes have been found to be excellent catalysts for carbenoid reactions such as C-H insertion and cyclopropanation, but have never before been shown to catalyze alkyne trimerization. These catalysts were found to trimerize alkynes to generate benzene derivatives in good yields with a similar efficiency to the literature results using conventional catalysts (up to 92% yield). The chirality of the rhodium(II) catalyst has no effect on the enantioselectivity of the trimerization. Asymmetric cyclopropanation of vinyl ethers using vinyldiazoacetates catalyzed by Rh 2 (S-DOSP) 4 has been achieved with high selectivity. The resulting vinylcyclopropanes have been found to undergo an acid catalyzed rearrangement to produce cyclopentenes. In an effort to illustrate the novel utility of this methodology by expansion into total synthesis of Beraprost, an incorrectly assigned structure in published work from the Davies group was uncovered. During the synthesis of the cyclopentene cyclic core of Beraprost, a cyclopropane ring expansion proceeded with unexpected regiochemistry. This outcome hindered any further development of the proposed synthetic route. A novel reaction, the C-H insertion/Cope rearrangement has been very useful at installing up to three stereocenters in a single step that can be used in total synthesis. (+)- Sinulobatin B is an example of a natural product that contains three stereocenters that can easily be synthesized from the combined C-H insertion/Cope reaction. Through an enantiodivergent step, a key intermediate for this compound can be produced. Although an aromatization reaction that could not be hindered was problematic in this synthesis, a highly substituted tricyclic ring system was still synthesized. Siloxyvinyldiazoacetates have not been investigated fully to this point. A study was undertaken to learn more about the reactivity of this diazo compound and the different influences on reactivity of the chiral catalysts Rh 2 (S-DOSP) 4 and Rh 2 (SPTAD) 4 . Dihydronaphthalenes have been found to be excellent substrates for the C-H insertion/Cope rearrangement with other vinyldiazoacetates, but also undergo competing cyclopropanation reactions. Therefore this diazo compound has been studied to find out what governs whether the C-H/Cope reaction or cyclopropanation is the dominant reaction pathway. Previously in the Davies group a study was undertaken to find out what governs rhodium(II) catalyzed carbenoid transformations of C-H insertion versus cyclopropanation of trans -olefins. This study was reinvestigated with highly activated trisubstituted olefins. Although the reaction of trisubstituted olefins produced cyclopropanes of trans -configuration, further investigation was done into the controlling factors in the production of cis versus trans cyclopropanation of 1,1-disubstituted olefins. Optimization of this reaction was accomplished by varying the catalyst, aryldiazoacetate and substrate used. Throughout this research, diazoacetates can undergo carbene dimerization. Although in well-planned reactions carbene dimerization can be avoided, systems lacking reactive trapping agent can lead to carbene self condensation. This study explores some of the previously reported dimer or even trimer formation pathways along with newly discovered dimers and other byproducts.