Asymmetric phosphine-mediated condensation reactions

Asymmetric synthesis, the ability to control the three-dimensional structure of a molecule, has revolutionized the advance of new and efficient catalysts within organic chemistry. The development of organic molecules of low molecular weight acting as catalysts, without the use of any metals, has burgeoned. The variety of chiral hydrogen-bond donors that have been developed and applied to asymmetric synthesis indicates the high synthetic value of these as organocatalysts. A review which demonstrates the power of asymmetric Bronsted acid-catalyzed reactions within synthetic organic chemistry is presented.; Through investigations of the metal alkoxide-promoted Morita--Baylis--Hillman reaction, an asymmetric Bronsted acid-catalyzed reaction was discovered. The reaction was developed into a highly enantioselective procedure for the addition of 2-cyclohexen-1-one to aldehydes promoted by triethylphosphine and a catalytic amount of a BINOL-derived Bronsted acid. The desired allylic alcohol products are provided in good yields and in up to 96% enantiomeric excess for a variety of aldehydes. This asymmetric Bronsted acid-catalyzed Morita--Baylis--Hillman reaction is a unique addition to the area of organocatalysis in that an organic promoter and chiral, hydrogen-bond-donating organic catalyst are necessary for the reaction to proceed.; An in-depth study of the mechanism of the asymmetric Morita--Baylis--Hillman reaction catalyzed by chiral Bronsted acids was undertaken. Nonlinear effect results, experimental and computational kinetic studies, and X-ray crystallographic and NMR analyses revealed a complex mechanism through which the condensation occurs. The optimized 3,3'-diaryl BINOL-derived Bronsted acid used to achieve optimum enantioselectivity was found to have a pronounced effect on reaction rate. A detailed mechanistic model is proposed which accounts for the observed effects.; Phosphines were found to mediate the highly diastereoselective synthesis of bicyclo[3.2.1]octenones from 1,4-dien-3-ones. The highly functionalized products were formed in good yields under the optimized conditions for various aromatic ketones, which condense in the presence of diethylphenylphosphine, and aliphatic ketones, which require the use of tributyphosphine. Mechanistic studies support a domino formal [4 + 2] cycloaddition-Wittig reaction mechanism. Cyclopentenone products can be synthesized via a similar domino Michael-Wittig reaction mechanism from isopropenyl phenyl ketone.