The chiral, nucleophilic catalyst TADMAP (1) has been prepared from 3-lithio-4-dimethylaminopyridine (5) and triphenylacetaldehyde (3), followed by acylation and resolution. TADMAP catalyzes the carboxyl migration of oxazolyl, furanyl, and benzofuranyl enol carbonates with good to excellent levels of enantioselection. The oxazole reactions are especially efficient, and are used to prepare chiral lactams (23) and lactones (30) containing a quaternary asymmetric carbon. TADMAP-catalyzed carboxyl migrations in the indole series are relatively slow and proceed with inconsistent enantioselectivity. Modeling studies (B3LYP/6-31G*) have been used in qualitative correlations of catalyst conformation, reactivity, and enantioselectivity.
TADMAP (1a), a new chiral DMAP catalyst, has been designed to place a C(3)-benzylic trityl group over one face of the pyridine ring, while a C(3)-benzylic acetoxy group creates a chirotopic environment on the other face. TADMAP was prepared in four steps (37% overall) from triphenylacetic acid and (dimethylamino)pyridine and was resolved using camphorsulfonic acid. TADMAP catalyzes the enantioselective rearrangement from oxazolyl phenyl carbonates 4 to azlactones 5, from furanyl phenyl carbonate 8 to the furanone 9, from the benzofuranyl carbonates 11a and 11b to benzofuranones 12a and 12b, and from the indolyl carbonates 11c and 11d to oxindoles 12c and 12d. The products are formed in good yield and, in most cases, with practical levels of enantiomer excess at the newly formed quaternary carbon.
The effects of the solvent, temperature, presence of lithium salts in the medium, and acidity of the proton source on enantioselective protonation with R-sulfinyl alcohols 2a-e were studied. Stereoselectivity was generally enhanced when lithium bromide was present in the medium during enolization and also with the use of methylene chloride solutions. Conversely, the optimal reaction temperature varied with the R-sulfinyl alcohol used as a proton source, and its effect appears to be related to both the acidity of the proton source and the enolate structure. R-Sulfinyl alcohols 2a and 2b gave the best results when the reactions were carried out at -100°C, while the optimal temperature with 2c was -78°C. The same ee values were obtained with 2d and 2e at either -100 or -78°C. In addition, an efficient synthesis of R-sulfinyl alcohols 2b and 2c is described.
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