The development of a catalytic asymmetric three–component Ugi reaction is described. The first chiral catalyst for the three–component Ugi reaction was identified as a result of a screen of a large set of different polyborate catalysts (BOROX catalysts). The BOROX catalysts were assembled in situ from a chiral biaryl ligand, an amine, water, BH3·SMe2, and an alcohol or phenol. The optimal catalyst system (LAP 78-5-47) provided α-amino amides from an aryl aldehyde, a secondary amine, and an isonitrile with high asymmetric induction. It is considered likely that the BOROX bind to the iminium ion or nitrilium ion as a chiral counter anion catalyst, as suggested by 1H and 11B NMR studies.The second project involves the application of BOROX–catalyzed aziridination to the synthesis of β–amino esters. A general study is undertaken to examine the scope of the reductive ring-opening of aziridine–2–carboxylates with samarium diiodide. The competition between C–C and C–N bond cleavage is examined as a function of the nature of the N–substituent of the aziridine, the nature of the substituent in the 3–position of the aziridine and on whether the substituent in the 3–position is in a cis- or trans–relationship with the carboxylate in the 2–position. Exclusive formation of the C–N cleavage product is observed for all aziridines with the strongly N–activating p–toluene sulfonate group. Nearly as high a selectivity is observed for the 2–trimethylsilylethyl sulfonate group (SES) which is easier to remove. The utility of these methods is illustrated in the synthesis of (3–DOPA and L–DOPA from the same aziridine, the former by SmI2 mediated reductive opening at C–2 and the latter by palladium mediated reductive opening at C–3.Lastly, the BOROX–catalyzed asymmetric aziridination is applied in the studies of total synthesis of one of the “two–headed” sphingoid bases, rhizochalinin C. The synthesis of left head 168 and right head 169 was developed. Late stage coupling of the two head-pieces provided the product with the complete carbon skeleton in high yield. The hydrogenation catalyzed by Pd(OH)2 in the presence of (Boc)2O successfully removed the two MEDAM groups, reduced the triple bond, removed the Bn group and reductively opened the aziridine ring. The final steps planned for the synthesis involving selective reduction of the carboxylic acid or the ester in the presence of a ketone failed to give any desired product. The synthesis will be further investigated.
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