Brønsted base catalysts.

Chiral organic Brønsted bases have emerged as highly efficient catalysts for enantioselective transformations. Since their early use in enantiomeric separation processes, chiral organic Brønsted base catalysis has advanced significantly to include both natural and designed catalysts. Insight into the mode of action of the organocatalysts has promoted modifications in catalyst structures to expand the application to numerous asymmetric reactions. Bifunctional catalysts, containing both Brønsted base and H-activating functionalities, have proven to be very applicable to an array of reaction types. The development of Brønsted base catalysts containing or not containing H-activating moieties, has greatly impacted asymmetric organocatalysis. This overview illustrates the recent developments in this emerging field.

Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides.

Herein an efficient and direct copper-catalyzed coupling of oxazoline-containing aryl bromides with electron-deficient secondary phosphine oxides is reported. The resulting tertiary phosphine oxides can be reduced to prepare a range of PHOX ligands. The presented strategy is a useful alternative to known methods for constructing PHOX derivatives.

A catalytic, asymmetric formal synthesis of (+)-hamigeran B.

A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.

High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates.

The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a non-polar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a ß-keto-ester derived- and an α-phenyl cyclohexanone-derived enol carbonate.

Skeletal diversity via cationic rearrangements of substituted dihydropyrans.

Substituted dihydropyrans, easily accessed from a commercially available glycal, undergo acid-catalyzed rearrangement to provide highly functionalized isochroman and dioxabicyclooctane scaffolds.

Asymmetric Morita-Baylis-Hillman reactions catalyzed by chiral Brønsted acids.

Chiral BINOL-derived Brønsted acids catalyze the enantioselective asymmetric Morita-Baylis-Hillman (MBH) reaction of cyclohexenone with aldehydes. The asymmetric MBH reaction requires 2-20 mol % of the chiral Brønsted acid 2e or 2f and triethylphosphine as the nucleophilic promoter. The reaction products are obtained in good yields (39-88%) and high enantioselectivities (67-96% ee). The Brønsted-acid-catalyzed reaction is the first example of a highly enantioselective asymmetric MBH reaction of cyclohexenone with aldehydes.