ENANTIOMERICALLY PURE DIHYDROPYRIMIDINONES AS REAGENTS AND AUXILIARIES FOR ASYMMETRIC-SYNTHESIS

We report herein full experimental details of the synthesis, structure, and reactivity of (R)- and (S)-2-tert-butyl-1-carbomethoxy-2,3-dihydropyrimidin-4-(1H)-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 N1 with the alpha,beta-unsaturated (vinylogous urea) system. In contrast, compound 11 [2-tert-butyl-3-((S)-O-methyl-mandeloyl)-2,3-dihydropyrimidin-4(1H)-one] shows strong coupling of N1 to the alpha,beta-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 beta-aryl-beta-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 alpha-substituted carboxylic acids. The crystalline properties of 1 and many of its derivatives allow for simplified purification procedures to be utilized.