Enantiomerically pure dihydropyrimidinones as reagents and auxiliaries for asymmetric synthesis

Article abstract of DOI:10.1021/ja00031a039

We report herein full experimental details of the synthesis, structure, and reactivity of (R)- and (S)-2-tert-butyl-l-carbomethoxy-2,3-dihydropyrimidin-4(lH)-one (1). The synthesis employs asparagine as the starting material and provides 1 in 55% yield without the need for Chromatographic purification. The structure of 1, as determined by X-ray crystallographic analysis, demonstrates significant pyramidalization at the C4 (carbonyl) and N1 centers, with little evidence of conjugation of Nl with the αβ,-unsaturated (vinylogous urea) system. In contrast, compound 11 [2-tert-butyl-3-((S)-O-methylmandeloyl)-2,3-dihydropyrimidin-4(lH)-one] shows strong coupling of Nl to the αβ,-unsaturated system, as evidenced by changes in bond lengths and torsional angles. Compound 1 has proven useful as a reagent for the synthesis of enantiomerically pure β-aryl-β-amino acids. The key step in this protocol is the palladium-catalyzed conjugate addition of aryl iodides to 1. Evidence is presented to support a mechanism for this reaction that involves an unprecedented transannular hydride transfer into the palladium coordination sphere. In additional experiments, 1 has been employed as an auxiliary for the synthesis of enantiomerically pure α-substituted carboxylic acids. The crystalline properties of 1 and many of its derivatives allow for simplified purification procedures to be utilized.