Discovery and development of novel reactions: Catalytic, asymmetric aldol-Tishchenko, Claisen, and diboration reactions

It was discovered that 10 mol% of Cr(ClO4)*6H2O could catalyze the intramolecular Cannizzaro reaction with iso-propanol. A series of high-throughput screenings led to the identification of a chiral Cu(II)-box complex as a potential chiral Lewis acid catalyst for the reaction. Selectivities remained low (33% e.e.), although catalyst loading could be lowered to 1 mol% without detrimental effects on product yields or selectivity. A cross-over experiment helped determine that hydride shift probably occurs in an intramolecular fashion.; Utilization of a chiral metal alkoxide library screening led to the discovery that an optimized yttrium (III)/salen complex could catalyze the aldol-Tishchenko reaction between iso-butyraldehyde and several aromatic aldehydes. The 1, 3-diol monoesters were prepared in up to 70% yield and 74% e.e. A postulated mechanism for the reaction was described, as well as a proposed model for asymmetric induction. Further studies on alpha, beta-unsaturated aldehydes were performed, including a focused screening of chiral metal alkoxides that all contained at least one acidic proton.; A library of chiral catalysts was screened for their effectiveness in the reductive ester enolate Claisen rearrangement of allylic acrylates. The results of the screen and the discovery that silyl ketene acetal was the reactive intermediate were presented. Use of a rhodium(I)/Me-Duphos catalyst allowed for selective formation of the (E)-silyl ketene acetal with allylic acrylates and therefore, a highly diastereoselective and mild Ireland-Claisen rearrangement under base-free conditions was discovered. Catalyst loading could be dropped to 0.5 mol% with no detrimental effects. Also, it was shown that the reaction is chemoselective as ester functionality survives the reaction untouched.; Finally, the discovery of a catalytic, enantioselective diboration of simple alkenes is discussed. It was discovered that 5 mol% of a rhodium(I)/( S)-Quinap catalyst complex and bis(catecholatodiboron) could perform the diboration of simple unfunctionalized alkenes. The products were isolated as the 1, 2-diols with yields of up to 76%, diastereomeric ratios >50:1, and >98% e.e. Further functionalization of the diborane intermediate was highlighted through transformation to the bis(pinacol) ester and homologation to the 1, 4-diol.