Enantioselective Alkynylation of Trifluoromethyl Ketones Catalyzed by Cation-Binding Salen Nickel Complexes.

Cation-binding salen nickel catalysts were developed for the enantioselective alkynylation of trifluoromethyl ketones in high yield (up to 99 %) and high enantioselectivity (up to 97 % ee). The reaction proceeds with substoichiometric quantities of base (10-20 mol % KOt-Bu) and open to air. In the case of trifluoromethyl vinyl ketones, excellent chemo-selectivity was observed, generating 1,2-addition products exclusively over 1,4-addition products. UV-vis analysis revealed the pendant oligo-ether group of the catalyst strongly binds to the potassium cation (K+ ) with 1:1 binding stoichiometry (Ka =6.6×105 m-1 ).

Copper-Catalyzed Enantioselective Allylic Alkylation with a γ-Butyrolactone-Derived Silyl Ketene Acetal.

Herein, we report a Cu-catalyzed enantioselective allylic alkylation using a γ-butyrolactone-derived silyl ketene acetal. Critical to the development of this work was the identification of a novel mono-picolinamide ligand with the appropriate steric and electronic properties to afford the desired products in high yield (up to 96 %) and high ee (up to 95 %). Aryl, aliphatic, and unsubstituted allylic chlorides bearing a broad range of functionality are well-tolerated. Spectroscopic studies reveal that a CuI species is likely the active catalyst, and DFT calculations suggest ligand sterics play an important role in determining Cu coordination and thus catalyst geometry.

Palladium-Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ-Lactams with Aryl Chlorides and Bromides.

Herein, we report the first Pd-catalyzed enantioselective arylation of α-substituted γ-lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron-rich dialkylphosphine ligand we have been able to construct α-quaternary centers in good yields (up to 91 % yield) and high enantioselectivities (up to 97 % ee).

Nickel-catalyzed enantioselective allylic alkylation of lactones and lactams with unactivated allylic alcohols.

The first nickel-catalyzed enantioselective allylic alkylation of lactone and lactam substrates to deliver products bearing an all-carbon quaternary stereocenter is reported. The reaction, which utilizes a commercially available chiral bisphosphine ligand, proceeds in good yield with a high level of enantioselectivity (up to 90% ee) on a range of unactivated allylic alcohols for both lactone and lactam nucleophiles. The utility of this method is further highlighted via a number of synthetically useful product transformations.

Control of Chemo-, Regio-, and Enantioselectivity in Copper Hydride Reductions of Morita-Baylis-Hillman Adducts.

Nonracemically ligated copper hydride can be used to effect tandem SN2'/1,2-reductions of racemic Morita-Baylis-Hillman (MBH) acetates to access enantioenriched chiral allylic alcohols with defined olefin geometry. MBH esters, including those with ß-substitution, can be transformed to stereodefined enoates by taking advantage of a bulky, oligomeric, in situ generated trialkoxysiloxane leaving group. Finally, an atypical conversion of easily arrived at MBH alcohol derivatives to nonracemic allylic alcohols is disclosed.

Stereoselective silylcupration of conjugated alkynes in water at room temperature.

Micellar catalysis enables copper-catalyzed silylcupration of a variety of electron-deficient alkynes, thereby providing access to isomerically pure E- or Z-ß-silyl-substituted carbonyl derivatives. These reactions take place in minutes, afford high yields and stereoselectivity, and are especially tolerant of functional groups present in the substrates. The aqueous reaction medium has been successfully recycled several times, and a substrate/catalyst ratio of 10,000:1 has been documented for this methodology.