Asymmetric 1,4-addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a chiral rhodium complex

Highly enantioselective 1,4-addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds was found to be catalyzed by a chiral rhodium complex generated from [Rh(cod)(MeCN)(2)]BF(4) and (S)-BINAP. Both (E)- and (Z)-1-alkenyl groups as well as aryl groups can be introduced enantioselectively into the beta-position of a variety of ketones, esters, and amides. [reaction--see text]     

Palladium-catalyzed conjugate addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds and nitroalkenes

The addition of aryltrialkoxysilanes to alpha,beta-unsaturated carbonyl compounds (ketones, aldehydes) and nitroalkenes in the presence of SbCl(3), TBAF, AcOH, and a catalytic amount of Pd(OAc)(2), in CH(3)CN at 60 degrees C, provides the corresponding conjugate addition products in moderate to good yields. The addition of equimolar amounts of SbCl(3) and TBAF is necessary for this reaction to proceed smoothly. The arylpalladium complex, which is generated by the transmetalation from a putative hypercoordinate silicon compound, is considered to be the catalytically active species.     

Asymmetric conjugate addition of carbonyl compounds to nitroalkenes catalyzed by chiral bifunctional thioureas

Readily available chiral thioureas derived from cyclohexane-1,2-diamine were prepared and found to be highly effective organocatalysts for the conjugate addition of aldehydes and ketones to nitroalkenes. Excellent enantioselectivities and yields were obtained for a variety of aryl and heteroaryl nitroalkenes. The base additives are essential for good yields and excellent enantioselectivities in this transformation. Based on new experimental evidence, a modified catalytic mechanism was proposed to rationalize the important role of the base additives.     

Reagent-controlled stereoselectivity in titanocene-catalyzed epoxide openings: reductions and intermolecular additions to alpha,beta-unsaturated carbonyl compounds

The generation and addition reactions of metal bound radicals derived from normal and meso epoxides by electron transfer from titanocene(III) reagents is described. The control of enantioselectivity and diastereoselectivity of these transformations is investigated by variation of the ligands of the metal complex. The reaction can lead to unprecedented and highly selective reactions, in which synthetically useful alcohols may be prepared. The synthesis presented also circumvents the use of toxic metals. Another advantage is that there is no loss of two functional groups as usually observed in reductive radical chain reactions.     

Pd(II)-bipyridine catalyzed conjugate addition of arylboronic acid to alpha,beta-unsaturated carbonyl compounds

[Reaction: see text]. A Pd(II)-catalyzed conjugate addition of arylboronic acid to alpha,beta-unsaturated ketones, aldehydes, esters, etc. in the presence of 2,2'-bipyridine was developed. A mechanism involving transmetalation, insertion of the carbon-carbon double bond into the C-Pd bond, and protonolysis of the resulting C-Pd bond is proposed. The reaction conditions are mild and the yield is high. The presence of 2,2'-bipyridine is crucial for the reaction to inhibit beta-hydride elimination.     

Synthetic applications of beta-fluoroalkylated alpha,beta-unsaturated carbonyl compounds

Beta-fluoroalkylated alpha,beta-unsaturated carbonyl compounds constitute efficient building blocks for the synthesis of complex fluorinated compounds. As the fluorinated moiety generally increases their reactivity, it also brings important modifications which can change the chemical behavior and selectivity. Their use has been already largely demonstrated. Nevertheless, the synthetic potential has not yet been fully explored and, consequently should play an important role in the design of new sophisticated fluorinated molecules. Nevertheless, it shall be important to develop new synthetic methods to enlarge their availability and their diversity.     

Amine-catalyzed addition of azide ion to alpha,beta-unsaturated carbonyl compounds

[formula: see text] A new protocol for the beta-azidation of alpha,beta-unsaturated carbonyl compounds is described. The method employs tertiary amines as catalysts for azide addition. The azide source is a 1:1 mixture of TMSN3 and AcOH. Tertiary amines, either in solution or bound to a solid support, are efficient catalysts for the reaction.     

Asymmetric conjugate addition of copper reagents to alpha,beta-unsaturated tert-butanesulfinyl imines

[reaction: see text] Addition of organocuprates to N-sulfinyl alpha,beta-unsaturated imines proceeds in good yields and with good diastereoselectivities. alpha,beta-Unsaturated sulfinyl ketimines and aldimines have both been shown to be suitable substrates for this reaction.     

Highly versatile enantioselective conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters

Herein, we report efficient catalysts for the asymmetric copper-catalyzed conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters. MeMgBr adds to aromatic alpha,beta-unsaturated thioesters with excellent enantioselectivities and moderate to good yields using Josiphos/CuBr and Tol-BINAP/CuI complexes. The use of bulky Grignard reagents leads to unprecedented enantioselectivities in the 1,4-addition to a broad range of aromatic and aliphatic alpha,beta-unsaturated thioesters using Tol-BINAP/CuI. The highest enantioselectivities reported so far for the addition of Grignard reagents to crowded beta-substituted aliphatic substrates are achieved with Tol-BINAP/CuI.     

Rhodium-catalysed 1,4-addition of diarylindium hydroxides to alpha,beta-unsaturated carbonyl compounds

Diarylindium(III) hydroxides react with alpha,beta-unsaturated carbonyl compounds in the presence of a rhodium catalyst to afford the 1,4-addition products in high yield. This reaction demonstrates the utility of diarylindium(III) hydroxide as an aryl source with rhodium catalysts.     

beta-Sulfinyl alpha,beta-unsaturated carbonyl compounds from enantiomerically pure sulfenic acids.

The addition of enantiopure sulfenic acids to oxoalkynes constitutes a new and efficient methodology for the synthesis of beta-sulfinyl alpha,beta-unsaturated carbonyl compounds. Sulfenic acids 3 and 4 were generated by thermolysis of suitable precursors and trapped in situ by oxoalkynes 5, affording (R(S),E)- and (S(S),E)-3-alkylsulfinyl-1-phenyl-2-propen-1-ones, 4-alkylsulfinyl-3-buten-2-ones, and 3-[(1S)-isoborneol-10-sulfinyl]-2-propenoates 6 and 7 in good yields and in enantiomerically pure form after simple column chromatography. (R(S),E)-3-[(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen-1-one (6(R)a) was involved as a heterodiene in inverse-electron-demanding Diels-Alder reactions with readily available electron-rich dienophiles 14 and 15, corroborating in each case the sulfinyl auxiliary capability in controlling the stereochemical outcome of these cycloadditions. Furthermore, the addition of methylmagnesium iodide to the carbonyl moiety of 6(R)a demonstrated that the chiral sulfur atom exerts a remote stereocontrol in this reaction if assisted by the hydroxy group being part of the isoborneol substituent.     

Asymmetric conjugate reduction of alpha,beta-unsaturated ketones and esters with chiral rhodium(2,6-bisoxazolinylphenyl) catalysts

New asymmetric conjugate reduction of beta,beta-disubstituted alpha,beta-unsaturated ketones and esters was accomplished with alkoxylhydrosilanes in the presence of chiral rhodium(2,6-bisoxazolinylphenyl) complexes in high yields and high enantioselectivity. (E)-4-Phenyl-3-penten-2-one and (E)-4-phenyl-4-isopropyl-3-penten-2-one were readily reduced at 60 degrees C in 95 % ee and 98 % ee, respectively, by 1 mol % of catalyst loading. (EtO)2MeSiH proved to be the best hydrogen donor of choice. tert-Butyl (E)-beta-methylcinnamate and beta-isopropylcinnamate could also be reduced to the corresponding dihydrocinnamate derivatives up to 98 % ee.     

Transition metal-catalysed acylation of alpha,beta-unsaturated carbonyl compounds with acylstannanes

Acylstannanes were found to add to such alpha,beta-unsaturated carbonyl compounds as enones or ynoates in the presence of a nicel or palladium catalyst to give 2-stannyl-4-oxoalk-2-enoates or 1,4-diketones, whereas the three component coupling between acylstannanes, enones and aldehydes provided 2-hydroxymethyl 1,4-diketones.     

Catalyst-free conjugated addition of thiols to alpha,beta-unsaturated carbonyl compounds in water

[reaction: see text] Catalyst-free conjugate addition of thiols to alpha,beta-unsaturated carbonyl compounds in water is reported. beta-Sulfido carbonyl compounds were formed at room temperature, in short times and with excellent chemoselectivity. Competitive dithiane/dithiolane formation, transesterification, and ester cleavage were not observed. Water played a dual role in simultaneously activating the alpha,beta-unsaturated carbonyl compound and the thiol. This new methodology constitutes an easy, highly efficient, and green synthesis of beta-sulfido carbonyl compounds.     

Samarium(II) iodide-mediated intramolecular conjugate additions of alpha,beta-unsaturated lactones

Samarium(II) iodide, in the presence of catalytic amounts of nickel(II) iodide, has been used to promote intramolecular conjugate additions of alkyl halides onto alpha,beta-unsaturated lactones. This process has been shown to be applicable to a number of alpha,beta-unsaturated lactones, including tetrasubstituted olefins, and has been demonstrated to be quite general for the formation of saturated bicyclic and tricyclic lactones. The method presented herein provides a mild, efficient process to form structurally complex lactones from simple precursors.