Using Fluorophobicity in Pd-catalyzed C-O Couplings

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DESCRIPTION (provided by applicant): The goal of this proposal is the expansion of the utility of palladium-catalyzed C-O bond-forming cross-coupling reactions through fluorophobic acceleration. Novel protocols for the general and mild formation of aryl and diaryl ethers are advanced in which the intrinsic fluorophobicity of aryl, alkenyl, and alkyl units is exploited to expedite product formation through fluorophobic packing in the transition state of reductive elimination. On account of the ubiquity of aryl ethers in biologically-active molecules, it is an important challenge to develop a general catalytic method to produce this structural motif. The formation of diaryl, aryl-allyl, and aryl-alkyl ethers is addressed. In the case of aryl-allyl ether formation, it is proposed that a Claisen rearrangement, which is also accelerated in fluorous solvents, will quickly follow reductive elimination. Any chirality that is pre-installed into the allylic alcohol unit will be transferred into the product of the Claisen rearrangement, leading to the potential formation of a chiral quaternary center. Thus, a simple and cheap entry into complicated chiral building blocks for potential use in pharmaceutical synthesis is also advanced.