Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Patrick J. Walsh

Abstract

Transition metal catalyzed C-C bond and C-S bond forming reactions offer a new opportunity to construct sulfur-containing compounds. However, preparation of sulfoxides through this pathway remains sporadic, probably due to the very weakly acidic -protons or instability of sulfenate anion, a key nucleophile to produce sulfoxides. To this end, this dissertation investigated the novel approaches to prepare sulfoxides via palladium catalyzed -arylation of methyl sulfoxides and S-arylation of sulfenate anions.

In chapter 1, the palladium catalyzed alpha arylation of unactivated sulfoxides is introduced. The weakly acidic alpha protons of sulfoxides are reversibly deprotonated by LiOtBu, and an indole-based phosphine ligated palladium complex facilitates the arylation reactions. A variety of (hetero)aryl methyl sulfoxides were successfully cross coupled with aryl bromides. More challenging coupling partners, such as alkyl methyl sulfoxides (including DMSO) proved to be suitable under the optimized conditions. Moreover, aryl chlorides were employed as electrophiles in our protocol by using Buchwald-type precatalyst. This method was utilized to synthesize bioactive benzyl sulfoxide intermediates

In chapter 2, we presented a novel approach to produce diaryl sulfoxides from aryl benzyl sulfoxides. Optimization of the reaction conditions was led by High-Throughput Experimentation (HTE) techniques. A single Pd(dba)2/NiXantPhos based catalyst successfully promotes a triple relay process involving sulfoxide -arylation, C-S bond-cleavage, and C-S bond-formation. Byproduct benzophenone is formed by an additional palladium-catalyzed process. It is noteworthy that palladium catalyzed benzylative substitution to cleavage C-S bond of sulfoxides is unprecedented. A wide range of (hetero)aryl benzyl sulfoxides, as well as alkyl benzyl sulfoxides with various (hetero)aryl bromides were employed in the triple relay process in good to excellent yields (85-99%). Moreover, aryl methyl sulfoxides, dibenzyl sulfoxides and DMSO could be utilized to generate diaryl sulfoxides involving multiple catalytic cycles by a single catalyst.

In chapter 3, we investigated diaryl sulfoxides generation from aryl benzyl sulfoxides and aryl chlorides via three sequential catalytic cycles all promoted by a NiXantPhos-based palladium catalyst. The key step is S-arylation of a sulfenate anion. An air- and moisture-stable palladacyclic precursor derived from NiXantPhos efficiently facilitated the transformation. Various functional groups, especially those with acidic protons, were tolerated. This method can also be extended to methyl and dibenzyl sulfoxides substrates

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