Asymmetric addition to chiral naphthalenes 5. An approach to the chlorothricolide system

Abstract

The asymmetric synthesis of several analogs of the so-called bottom half of chlorothricolide has been accomplished. The key reaction involves addition of a pentenyl lithium to the chiral naphtyl oxazoline 2 followed by methyl iodide quench to afford the quaternary tetralin system 3. Further elaboration and Birch reduction gave the hexahydro- naphthalene 9 which readily transformed into the bottom-half analogs 15, 18, 22, and 24. Unfortunately, none of these corresponded to the correct stereochemical configuration of the natural bottom half degradation product. Extensive NMR studies confirmed the stereochemistry of the products analogues to the latter and showed that the metal-ammonia reductions or the catalytic hydrogenation studies were inappropriate methods to reduce aromatic or dihydro analogs to the natural configuration.