One-pot terminal alkene homologation using a tandem olefin cross-metathesis/allylic carbonate reduction sequence

A one-carbon homologation of terminal alkenes has been developed utilizing an olefin cross-metathesis followed by a palladium-mediated allylic carbonate reduction; various substrates were used to demonstrate the scope of the reaction, with yields ranging from 65 to 86%.     

Inositols as chiral templates: 1,4-conjugate addition to tethered cinnamic esters

The 1,4-addition of thio nucleophiles to chiro-inositols containing a cinnamyl Michael acceptor proceeded with excellent diastereochemical induction and good yields. Cleavage of the inositol auxiliary provides beta-thio hydrocinnamic acids in >99% ee's.     

Rhodium catalyzed 1,4-conjugate addition of 1,5-azastibocines with electron deficient olefins

The rhodium-catalyzed reaction of Sb-aryl-1,5-azastibocines with alpha,beta-unsaturated ketones and esters is described. Exclusive formation of 1,4-conjugate adduct was achieved in aqueous NMP (N-methyl-2-pyrrolidinone) in the presence of 5 mol% of [RhCl(cod)](2), and no formation of Heck adduct was observed in this condition. Reactions with various enones and enoates were also demonstrated to prove generality of the 1,4-conjugate addition.     

One-pot synthesis of benzofused heteroaryl azoles via tandem C-heteroatom coupling/C-H activation of azoles

The Cu(I) or Pd(II)-catalyzed cross-couplings of gem-dihaloolefins with azoles via tandem C-heteroatom coupling/C-H activation for the preparation of benzofused heteroaryl azoles have been developed.     

Advances on asymmetric organocatalytic 1,4-conjugate addition reactions in aqueous and semi-aqueous media

Asymmetric Michael addition reactions or 1,4-conjugate addition reactions are considered to be the fundamental C–C bond-forming reaction for the construction of chiral β-nitro, β-carbonyl and several other important structural motifs in organic synthesis. After the development of many chiral metal complexes as catalysts, a tremendous growth in the design and applications of variety of new chiral organocatalysts for asymmetric 1,4-conjugate addition reactions has been witnessed over the last two decades. Initially, asymmetric organocatalysis has been performed in organic solvents, but gradually performing the same catalysis in aqueous and semi-aqueous media became a necessity due to environmental aspects as well as to achieve better reactivity and selectivity. The structural and functional diversity of the chiral organocatalysts derived from natural and synthetic sources utilized differently the water either as the sole solvent, co-solvent or additive for optimising their best performances. In the present review, we discuss a detailed and comprehensive report on the advancement in the field of asymmetric organocatalytic 1,4-conjugate addition reactions in aqueous and semi-aqueous media.     

The ortho effect: copper-catalyzed highly enantioselective 1,4-conjugate addition of diethylzinc to chalcones

The copper-catalyzed enantioselective 1,4-conjugate addition of diethylzinc to chalcones was investigated in the presence of a catalytic amount of N,P-ferrocenyl ligands with central and planar chirality under mild conditions (0 °C→rt). It was found that chalcones with ortho-substituents (from ortho-substituted benzaldehydes and acetophenone/substituted acetophenones) led to a dramatic improvement in the enantioselectivities. The (R)- and (S)-antipodes of the addition reaction were obtained with up to 92% ee after this transformation.     

The first examples of rhodium-catalyzed 1,4-conjugate addition reactions of arylboronic acids with ethenesulfonamides

An unprecedented rhodium-catalyzed 1,4-conjugate addition of arylboronic acids with ethenesulfonamides resulting in the corresponding 2-arylethanesulfonamides is described. The amino substituent, the applied arylboronic acid, the type of Rh-catalyst, and the experimental conditions all affected the reaction outcome.     

(R)-4-menthenone in reactions of 1,4-conjugate and 1,3-dipolar addition

(R)-4-Menthenone compared with common cyclic enones exhibits considerably lower reactivity in 1,4-conjugate addition of organometallic reagents, is inert in Michael reactions and pyrazoline formation evidently due both to the distorted polarization in the enone system and to steric hindrances from the α-isopropyl group in the cyclohexene ring.     

Enantioselective 1,4-conjugate addition of diethylzinc to (E)-alkenyl aryl ketones catalysed by Cu/DiPPAM complex

We report here the use of the DiPPAM-L1 ligand for copper-catalysed asymmetric conjugate addition (ACA) of diethylzinc to various (E)-alkenyl aryl ketones where the aryl ring is either a phenyl group substituted by nitro, chloro or methoxy groups or not substituted, or a naphthyl group. When the conjugate addition was performed in the greener AcOEt solvent with 1 or 2 mol % of Cu(OTf)₂/DiPPAM complex, moderate to good yields (45–83%) and high enantioselectivities (up to 98%) were reached.     

One-pot three-component synthesis of pyrazoles through a tandem coupling-cyclocondensation sequence

An efficient and general one-pot procedure for the synthesis of pyrazoles from acid chlorides, terminal alkynes and hydrazines was described via a coupling and cyclocondensation sequence. Acid chlorides coupled with terminal alkynes to give α,β-unsaturated ynones, and in situ converted into pyrazoles by the cycloaddition of hydrazines. The desired pyrazoles were obtained with 15-85% isolated yields.     

Iridium-catalyzed C-H activation/borylation/oxidation for the preparation of bis-protected phloroglucinol derivatives

The preparation of bis-protected phloroglucinol derivatives from a range of protected resorcinol substrates is presented. Functionalization was achieved via a two-step, one-pot iridium-catalyzed C-H activation/borylation/oxidation protocol. Our system gave high conversions to the arylboronic esters and good yields of the desired phenols following subsequent oxidation. A range of common protecting group categories was studied including alkyl, silyl, ether and ester.     

One-pot three-component tandem metathesis/Diels-Alder reaction

[reaction: see text] A tandem enyne, diene-ene metathesis reaction followed by Diels-Alder reaction accomplished a stereoselective three-component reaction protocol with four stereocenters.     

A rhodium-catalyzed C-H activation/cycloisomerization tandem

A reaction cascade comprising a rhodium-catalyzed C-H activation, a subsequent hydrometalation of an alkylidene cyclopropane in vicinity, regioselective C-C bond activation of the flanking cyclopropane ring, followed by reductive elimination of the resulting metallacycle, opens a new entry into functionalized cycloheptene derivatives. This crossover of C-H activation and higher order cycloaddition has been performed in two different formats, either using alkylidenecyclopropanes with a lateral vinylpyridine moiety or with a pending aldehyde group as the trigger. The reaction tolerates various functional groups, leaves chiral centers alpha to the reacting sites unaffected, and proceeds with excellent stereoselectivity. Labeling experiments support the proposed mechanism explaining the observed net cycloisomerization process.     

Catalytic direct 1,4-conjugate addition of aldehydes to vinylketones on secondary-amines immobilised in FSM-16 silica

Direct 1,4-conjugate addition of naked aldehydes to vinylketones is catalysed effectively by N-methyl-3-aminopropylated FSM-16 mesoporous silica, which can be regarded as a novel heterogeneous catalysis for a practical C-C bond formation reaction.     

Highly enantioselective 1,4-conjugate addition of dialkylzinc to α,β-unsaturated lactone catalyzed by diphosphite-copper complexes

The 1,4-addition of diethylzinc and dimethylzinc to 5,6-hydro-2H-pyran-2-one using new chiral diphosphite-copper catalysts gave products in up to 98% ee.     

New bis(1-ferrocenylethyl)amine-derived monodentate phosphoramidite ligands for highly enantioselective copper-catalyzed 1,4-conjugate addition

A new family of chiral bis(1-ferrocenylethyl)amine-derived monodentate phosphoramidite ligands has been prepared and successfully applied in the Cu-catalyzed asymmetric 1,4-conjugate addition of diethylzinc to a variety of α,β-unsaturated compounds, in which up to 99% ee was obtained for nitroalkenes at ?78 °C and >98% ee for cyclohexenone at ?30 °C, comparable to or higher than those obtained with the most efficient monophosphoramidite ligands reported so far.     

An enantioselective catalytic approach to syn deoxypropionate units combining asymmetric Cu-catalyzed 1,6- and 1,4-conjugate addition

A novel iterative approach to the synthesis of the naturally ubiquitous syn deoxypropionate motif is reported. The route comprises a new Horner–Wadsworth–Emmons reagent to prepare α,β,γ,δ-bisunsaturated thioesters. Next, two Me-substituents are introduced in high yield, regio- and enantioselectivity using sequential asymmetric Cu-catalyzed 1,6-conjugate addition, base-catalyzed olefin isomerization and Cu-catalyzed enantioselective 1,4-conjugate addition. After reduction to the aldehyde these transformations can be repeated to install three or more Me groups with a syn 1,3-relationship.     

One-pot borylation/amination reactions: syntheses of arylamine boronate esters from halogenated arenes

[reaction: see text] A one-pot protocol for converting 1,3- and 1,4-substituted aryl halides to arylamine boronate esters is described. This is achieved by sequential Ir-catalyzed aromatic borylation at the least hindered C-H bond of the aryl halide and subsequent Pd-catalyzed C-N coupling at the halide position of the crude arylboronic ester.     

Chiral pyrrolidinium salts as organocatalysts in the stereoselective 1,4-conjugate addition of N-methylpyrrole to cyclopent-1-ene carbaldehyde

A variety of enantiopure proline derived pyrrolidinium (HX)_n salts have been found to catalyse the 1,4-conjugate addition of N-methylpyrrole to cyclopent-1-ene carbaldehyde with, in some cases, high diastereo- and enantioselectivity. Parameters such as water activity, choice of acidic cocatalyst (HX)_n and also the amount of cocatalyst used turned out to be crucial for the diastereo- and enantioselectivity of the reaction.     

One-pot reductive cleavage of exo-olefin to methylene with a mild ozonolysis-Clemmensen reduction sequence

A one-pot exo-olefin reductive cleavage was for the first time developed. The reaction could proceed under a mild condition avoiding the use of hazardous and expensive reagents. Meanwhile, a TMSCl-mediated Clemmensen reduction in alcoholic solvent was also examined.