Evolution of anion relay chemistry (ARC): Design, synthesis and evaluation of effective bi-functional linchpins for type II ARC

This two parts dissertation describes the concept of A&barbelow;nion R&barbelow;elay C&barbelow;hemistry (ARC), an effective multi-component union protocol in conjunction with the design, synthesis and validation of viable bifunctional linchpins for Type II ARC.;Part I, Chapter one introduces Type I and II Anion Relay Chemistry (ARC) and describes further extensive studies of Type II ARC mediated by 1,4-C(sp 3)→O Brook Rearrangement.;Chapter two of Part I describes the feasibility of higher order rearrangement, namely [1,5]- and [1,6]-Brook rearrangements, in conjunction with their applications in Type II A&barbelow;nion R&barbelow;elay C&barbelow;hemistry (ARC) to expand the scope of ARC tactic.;Part II, Chapter three introduces examples employing 1,4-C(sp 2)→O Brook Rearrangement reported by the Keay, Moser, Takeda and Xian laboratory. The following four chapters (4-7) will then describe new classes of bifunctional linchpins for Type II ARC mediated by 1,4-C(sp 2)→O Brook Rearrangement.;Chapter four introduces the viability of ortho-TMS benzaldehyde as a new bifunctional linchpin for Type II ARC process. Co-addition of both Cul and HMPA was found to be critical to facilitate 1,4-C(sp2)→O Brook rearrangement via stabilization of the carbanion. The resultant aryl anion permits both alkylation and Pd-mediated C&barbelow;ross C&barbelow;oupling R&barbelow;eactions (CCR). Construction of the 24 possible congeners of a focused library of 10-membered "natural product-like" macrolides employing iterative Type II ARC process was achieved in 6 steps from 2-methyl-1,3-dithiane with an overall yield of 25% (i.e., 13% and 12%, respectively).;Chapter five describes one-pot syntheses of 2,3-disubstituted furans and thiophenes employing 2-TBS-3-formyl furan and thiophenes as the bifunctional linchpins via Type II ARC tactic. Central to this process is a solvent mediated 1,4-C(sp2)→ Brook rearrangement. Rapid construction of a 5-membered fused thiophene exploiting Type II ARC process was also achieved.;Chapter six illustrates a new class of three- and four-carbon bifunctional linchpins, comprising vinyl silanes bearing beta- or gamma-electrophilic sites. Here, we have designed, synthesized these linchpins and demonstrated their application in Type II ARC processes. This synthetic tactic permits not only alkylation but importantly Pd-mediated C&barbelow;ross C&barbelow;oupling R&barbelow;eactions (CCR) of the vinyl anion derived via 1,4-C(sp2)→O Brook rearrangement. To expand further the scope of Type II ARC tactic, we achieved the uniting of 1,2-diastereoselective induction and the Type II ARC process.;Chapter seven introduces a new class of bifunctional linchpins capable of generating benzyne intermediates via Type II Anion Relay Chemistry (ARC), that in turn undergo efficient inter- and intramolecular [2+2], [3+2] and [4+2] cycloadditions. (Abstract shortened by UMI.)...