FINE TUNING BINOLS AND BINAPS FOR ASYMMETRIC SYNTHESIS

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DESCRIPTION: (applicant's abstract) In the field of asymmetric synthesis, one of the most powerful approaches involves use of BINOL and BINAP ligands as catalysts. These binaphthylic species are among the most extensively utilized systems for inducing chirality into a vast array of intermediates of value en route to physiologically active compounds. Their involvement in such targets as naproxen (anti-inflammatory), morphine (narcotic), and dextromethorphan (cough suppressant) only begin to touch upon their importance to the pharmaceutical arena, where most new drugs must now be "chiral" (i.e., single enantiomer). Remarkably, however, there are very few substituted BINOLs known, and no substituted BINAPs, where any of the remaining positions on the naphthalene rings bear groups that might significantly improve enantioselectivity of numerous reactions which rely on one of these ligands. This proposal, therefore, seeks to address this fundamental problem; that is, of supplying methodology for arriving at substituted BINOLs and BINAPs. In particular, substitution at the 3- and 3,3'-positions will be addressed, as these sites can play a pivotal role in enhancing nonracemic binaphthyl-induced stereoinduction via steric factors and/or chelation properties. The key to providing such new ligands rests upon the attachment of the individual naphythylic components to a nonracemic tether, with subsequent intramolecular oxidative biaryl coupling to the corresponding, optically pure, substituted cyclo-BINOL array. From ligands of this type come further options, such as opportunities for polymer mounting, and potentially of greatest attention, conversion to substituted cyclo BINAPs.