| A major objective of organic synthesis is to develop environmentally benign and synthetically efficient reactions that employ inexpensive building blocks and catalysts. Towards this end, the development of molybdenum catalyzed asymmetric allylic alkylation reactions with oxindoles as nucleophiles is described. Molybdenum is one of the least expensive metals and the chiral ligand employed for the reaction is available in one-step from commercially available materials. The starting materials of the reaction, 3-mono-substituted oxindoles, are also readily accessible from inexpensive commercial reagents such as indoles and isatins. The products of molybdenum reactions, chiral 3-di-substituted oxindoles, are highly valuable, as they can be transformed into a variety of biologically relevant natural products. For example, short syntheses of (ent)-(-) debromoflustramine and (-)-physiostigmine were accomplished from products of the reaction between 3-alkyloxindoles and allyl tert-butyl carbonate.;Finally, progress towards the first enantioselective synthesis of perophoramidine is described. The key quaternary carbon center was assembled efficiently by employing the molybdenum reaction. A novel ring-closing strategy was discovered for the preparation of the indolinoquinoline ring, and the second vicinal quaternary center was constructed by a diastereoselective alkylation of a lactone. Model studies for the last steps of the synthesis are also discussed.;The molybdenum reaction is also of interest because it allows access to unusual regioselectivity in allylic substitution reactions compared to other metals. When unsymmetrical allylic electrophiles are employed, the molybdenum reaction generally favors nucleophilic attack at the more substituted allyl terminus to give the branched products, while the same reaction employing palladium generates the regioisomeric linear products. During our studies, the regioselectivity of the molybdenum reaction with oxindoles was found to be highly dependent on the electronic and steric properties of the oxindole nucleophiles. By careful tuning of the nucleophile, excellent levels of regio-, diastereo- and enantioselectivity were obtained for oxindoles with a variety of substitution patterns. |
