Beta-halo-alpha,beta-unsaturated gamma-sultones

The reaction of beta-iodo-alpha,beta-unsaturated gamma-sultones (i.e., 4-halo-1,2-oxathiole 2,2-dioxides) in aprotic polar solvents such as DMSO or acetone, with 'soft' nucleophiles such as iodide or thioacetate, yields an allenesulfonate by a very facile halophilic ring-opening E(2)-elimination. The 'harder' nucleophile, azide ion, reacts under the same conditions to yield the corresponding beta-azido-alpha,beta-unsaturated gamma-sultone (i.e., 4-azido-1,2-oxathiole 2,2-dioxide), displacing the beta-halide by an addition-elimination mechanism. In contrast, in the hydroxylic solvent CD(3)OD at ambient temperature, various nucleophiles yield neither of the above-mentioned products, but catalyze a rapid replacement of the Calpha-H by deuterium. Factors underlying this intriguing rapid exchange are proposed. Interestingly, the beta-bromo analogue exhibits similar reactivity except for the halophilic ring-opening. Calculations indicate the relative importance of the beta-halogen and the S-O(-C) bonds in enhancing the acidity of the H-C(alpha)S(O)2- grouping.     

Asymmetric Lewis acid-catalyzed Diels-Alder reactions of alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides

[reaction: see text] Conformational analysis, van der Waals attractions, and transition structure calculations are combined to design an asymmetric Lewis acid-catalyzed Diels-Alder reaction for simple acyclic alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides, giving up to 83 and 92% ee, respectively. The two-point-binding chiral recognition mechanism, Lewis acid-Lewis base coordination with boron and a van der Waals attraction with the naphthyl group, uses the inherent enone unit of simple alpha,beta-unsaturated carbonyl compounds, ending the need for auxiliary oxygen binding sites on the dienophile.     

Stereoselective synthesis of Z-alpha-aryl-alpha,beta-unsaturated esters

An efficient method for the stereoselective synthesis of (Z)-alpha-arylacrylates is described. Treatment of alpha-hydroxyesters with triflic anhydride and pyridine at 0 degrees C followed by warming to room temperature afforded the corresponding (Z)-alpha-aryl-alpha,beta-unsaturated esters in very good yields and excellent stereoselectivity.     

Catalytic asymmetric 1,4-addition reactions using alpha,beta-unsaturated N-acylpyrroles as highly reactive monodentate alpha,beta-unsaturated ester surrogates

Synthesis and application of alpha,beta-unsaturated N-acylpyrroles as highly reactive, monodentate ester surrogates in the catalytic asymmetric epoxidation and Michael reactions are described. alpha,beta-Unsaturated N-acylpyrroles with various functional groups were synthesized by the Wittig reaction using ylide 2. A Sm(O-i-Pr)(3)/H(8)-BINOL complex was the most effective catalyst for the epoxidation to afford pyrrolyl epoxides in up to 100% yield and >99% ee. Catalyst loading was successfully reduced to as little as 0.02 mol % (substrate/catalyst = 5000). The high turnover frequency and high volumetric productivity of the present reaction are also noteworthy. In addition, a sequential Wittig olefination-catalytic asymmetric epoxidation reaction was developed, providing efficient one-pot access to optically active epoxides from various aldehydes in high yield and ee (96-->99%). In a direct catalytic asymmetric Michael reaction of hydroxyketone promoted by the Et(2)Zn/linked-BINOL complex, Michael adducts were obtained in good yield (74-97%), dr (69/31-95/5), and ee (73-95%). This represents the first direct catalytic asymmetric Michael reaction of unmodified ketone to an alpha,beta-unsaturated carboxylic acid derivative. The properties of alpha,beta-unsaturated N-acylpyrrole are also discussed. Finally, the utility of the N-acylpyrrole unit for further transformations is demonstrated.     

Catalytic enantioselective peroxidation of alpha,beta-unsaturated ketones

Despite the potential of chiral peroxides as biologically interesting or even clinically important compounds, no catalytic enantioselective peroxidation has been reported. With a chiral catalyst not only to induce enantioselectivity but also to convert a well established epoxidation pathway into a peroxidation pathway, the first efficient catalytic peroxidation has been successfully developed. Employing readily available alpha,beta-unsaturated ketones and hydroperoxides and an easily accessible cinchona alkaloid catalyst, this novel reaction will open new possibilities in the asymmetric synthesis of chiral peroxides. Under different conditions a highly enantioselective epoxidation with the same starting materials, reagents, and catalyst has was also established.     

Metallophosphite-catalyzed asymmetric acylation of alpha,beta-unsaturated amides

The l-menthone-derived TADDOL phosphite 6b catalyzes highly enantioselective conjugate additions of acyl silanes to alpha,beta-unsaturated amides. p-Methoxybenzoyl cyclohexyldimethylsilane adds to a variety of N,N-dimethyl acrylamide derivatives in the presence of the lithium salt of 6b. In many instances the alpha-silyl-gamma-ketoamide product undergoes facile enantioenrichment (to 97-99% ee) upon recrystallization. Desilylation with HF.pyr affords the formal Stetter addition products. Baeyer-Villiger oxidation of the desilylated gamma-ketoamides affords useful ester products. An X-ray diffraction study of 6b reveals that the isopropyl group of the menthone ketal influences the position of the syn-pseudoaxial phenyl group in the TADDOL structure. Through a crossover experiment, the silicon migration step in the reaction mechanism is shown to be strictly intramolecular.     

Nornicotine-organocatalyzed aqueous reduction of alpha,beta-unsaturated aldehydes

Nornicotine, a native component of tobacco and minor nicotine metabolite, was found to catalyze the chemoselective reduction of alpha,beta-unsaturated aldehydes under homogeneous aqueous conditions.     

Asymmetric 1,4-hydrosilylations of alpha,beta-unsaturated esters

Complexing catalytic amounts of CuH with a nonracemic JOSIPHOS or SEGPHOS ligand, together with stoichiometric PMHS, leads to exceedingly efficient and highly enantioselective 1,4-reductions of beta,beta-disubstituted enoates and lactones. An unprecedented substrate-to-ligand ratio of 7700:1 for this type of reaction is documented.     

Palladium-catalyzed conjugate allylation reactions of alpha,beta-unsaturated N-acylpyrroles

Conjugate allylation reactions of alpha,beta-unsaturated N-acylpyrroles using allylboronic ester are catalyzed by a palladium complex that is ligated by a bidentate N-heterocyclic carbene. A variety of functional groups are tolerated, and substrates functionalized with electron-withdrawing groups react to afford the highest yields of products. Regioselectivity for 1,4-allylation over 1,2-allylation is demonstrated, and mechanistic experiments are consistent with formation of nucleophilic allylpalladium intermediates.