Chiral control is one of the most challenging current problems of organic chemistry, and experimental investigation of the interactions responsible for strong control is essential for future progress. In preliminary experiments, this laboratory has recently discovered that Diels-Alder reactions of 1-(O-methymandeloxy) dienes can be made to give diastereofacial selectivities in excess of 90%, shown that pi-stacking is not the controlling mechanism, and proposed a """"""""perpendicular model"""""""" for the transition state conformation which explains the observed diastereofacial selectivities. The distinctive characteristics of this perpendicular model are that the phenyl group is nearly perpendicular to the ester C=O, i.e., the Ph-C-C=O dihedral angle is near 90 degrees, and that the methoxy group is close to the carbonyl oxygen. The features of this model may well have wider applications for chiral control by alpha-chiral ester groups in other types of reactions. Arising from this laboratory's long-term research goal of >99% asymmetric control of C-C bond-forming reactions, the objective of the research proposed is to exploit asymmetric Diels-Alder and related reactions, especially to examine the scope of the new (still hypothetical) perpendicular model for O-methylmandelate derivatives, develop synthetically useful processes, and elucidate the actual origins of high stereoselectivities. The immediate target is to expand the scope, understanding, and synthetic utility of chiral dienes for control of asymmetric Diels-Alder reactions. This target arises from the relatively little work that has been done with chiral dienes plus the exciting initial results obtained in this laboratory. The significance of the proposed work lies in the fact that chiral molecules are extremely common in nature, and it is therefore very important to develop methods for preparing specific chiral molecules in the laboratory in order to study their reactions and their properties, particularly their physiological properties. Especially pertinent is synthesis of compounds which are rare or unstable in nature (not easily isolated directly from natural sources) and structures which do not occur in nature (e.g., enantiomers, which frequently do not appear in nature, as well as completely unnatural structures). Moreover, in order to design new systems for controlling stereoselectivity, regioselectivity, and/or chemoselectivity, it is essential to develop the experimental basis for reliable explanations, capable of predicting optimal means of control. Essential experimental methodology includes high-performance liquid chromatography, capillary-column gas-liquid chromatography, high-field nuclear magnetic resonance spectroscopy, automated X ray crystal structure determination, and high-resolution mass spectrometry.
| Johnson, K R (1993) Characterization of cDNA clones encoding the human homologue of Saccharomyces cerevisiae ribosomal protein L30. Gene 123:283-5 |
