Domino Michael/Michael reaction catalyzed by switchable modularly designed organocatalysts.

The domino Michael/Michael reaction between ()-7-aryl-7-oxohept-5-enals and -cinnamaldehydes was investigated by using modularly designed organocatalysts (MDOs). It was found that both the enamine and iminium catalytic modes of the MDOs are switchable and can be individually switched on and off by using appropriate combinations of the precatalyst modules and the reaction conditions. When both the enamine and iminium catalysis modes of the MDOs are switched on, the desired domino reaction products can be obtained in good yields and stereoselectivities under optimized conditions.

Diastereodivergent synthesis of 4-oxocyclohexanecarbaldehydes by using the modularly designed organocatalysts upon switching on their iminium catalysis.

The cinchona thiourea moiety in the self-assembled modularly designed organocatalysts (MDOs) switches off the iminium catalysis of these catalysts. In this study, it was found that the inhibited iminium catalysis could be switched on by using an appropriate weak acid and that, once the iminium catalysis was switched on, these catalysts could be applied for the highly stereoselective and diastereodivergent synthesis of 4-oxocyclohexanecarbaldehydes via a domino reaction between ketones and α,β-unsaturated aldehydes.

Stereoselective Synthesis of 3-Oxabicyclo[3.3.1]nonan-2-ones via a Domino Reaction Catalyzed by Modularly Designed Organocatalysts.

A highly stereoselective method for the synthesis of functionalized 3-oxabicyclo[3.3.1]nonan-2-one derivatives with four contiguous stereogenic centers, including one tetrasubstituted stereogenic center, was realized through an organocatalytic domino Michael-hemiacetalization-Michael reaction of ()-3-aryl-2-nitroprop-2-enols and ()-7-aryl-7-oxohept-5-enals followed by a PCC oxidation.

Diastereodivergent Synthesis of Hexahydro-6H-benzo[c]chromen-6-one Derivatives Catalyzed by Modularly Designed Organocatalysts.

The diastereodivergent synthesis of hexahydro-6H-benzo[c]chromen-6-one derivatives with good to high diastereoselectivities (up to 98:2 d.r.) and enantioselectivities (up to >99 % ee) has been achieved by using a domino Michael/Michael/hemiacetalization reaction between trans-2-hydroxy-β-nitrostyrenes and trans-7-oxo-5-heptenals followed by oxidation.

Stereoselective synthesis of chromane derivatives via a domino reaction catalyzed by modularly designed organocatalysts.

A highly enantio- and diastereoselective method for the synthesis of functionalized chroman-2-ones and chromanes was achieved by using an organocatalytic domino Michael/hemiacetalization reaction of aliphatic aldehydes and (E)-2-(2-nitrovinyl)phenols followed by a PCC oxidation and dehydroxylation, respectively. Using the modularly designed organocatalysts (MDOs) self-assembled from cinchona alkaloid derivatives and amino acids in the reaction media, the title products were obtained in good to high yields (up to 97%) and excellent diastereoselectivities (up to 99 : 1 dr) and enantioselectivities (up to 99% ee).

Pd(II)-Catalyzed Arylation and Intramolecular Amidation of γ-C(sp)-H Bonds: En Route to Arylheteroarylmethane and Pyrrolidone Ring Annulated Furan/Thiophene Scaffolds.

We report the Pd(II)-catalyzed, bidentate directing group (BDG)-assisted arylation and successive arylation/intramolecular amidation of γ-C(sp)-H bonds. The Pd(II)-catalyzed BDG-assisted C-H activation and functionalization of the β-C(sp)-H bonds of carboxylic acids are well documented, but only a few reports are available that deal with the BDG-directed functionalization of the γ-C(sp)-H bonds. Various 3-methylthiophene/furan-2-carboxamides (1a-e) were derived from their corresponding carboxylic acids and bidentate directing groups.

Pd(II)-Catalyzed, Picolinamide-Assisted, Z-Selective γ-Arylation of Allylamines To Construct Z-Cinnamylamines.

Investigations of Pd(II)-catalyzed, picolinamide-assisted, γ-C(sp)-H activation and Z-selective arylation of allylamines are reported. The reactions of N-allylpicolinamides with various aryl iodides in the presence of the catalyst Pd(OAc) and additive AgOAc have led to the selective γ-arylation of allylamines to construct various cinnamylamines with moderate to good yields and good to high E/Z ratios. To obtain good E/Z ratios, the Pd(II)-catalyzed arylation reaction of N-allylpicolinamides was probed using different additives, directing groups, and reaction conditions.

4-Amino-2,1,3-benzothiadiazole as a Removable Bidentate Directing Group for the Pd(II)-Catalyzed Arylation/Oxygenation of sp/sp β-C-H Bonds of Carboxamides.

In this paper, we report 4-amino-2,1,3-benzothiadiazole (ABTD) as a new bidentate directing group for the Pd(II)-catalyzed sp/sp C-H activation/functionalization of various aliphatic/alicyclic/aromatic carboxamide systems. The Pd(II)-catalyzed, ABTD-directed sp C-H arylation/acetoxylation of aliphatic- and alicyclic carboxamides afforded the corresponding β-C-H arylated/acetoxylated carboxamides. The Pd(II)-catalyzed, ABTD-directed sp C-H arylation of cyclobutanecarboxamide with different aryl iodides afforded the corresponding bis β-C-H arylated cyclobutanecarboxamides having all-cis stereochemistry with a high degree of stereocontrol.

Diastereoselective Pd(II)-Catalyzed sp C-H Arylation Followed by Ring Opening of Cyclopropanecarboxamides: Construction of anti β-Acyloxy Carboxamide Derivatives.

The diastereoselective Pd(OAc)-catalyzed, bidentate ligand-directed sp C-H activation/arylation followed by ring opening of cyclopropanecarboxamides, which were assembled from cyclopropanecarbonyl chlorides and bidentate ligands (e.g., 8-aminoquinoline and 2-(methylthio)aniline), has been investigated.

Pd(OAc)2-Catalyzed, AgOAc-Promoted Z Selective Directed β-Arylation of Acrylamide Systems and Stereoselective Construction of Z-Cinnamamide Scaffolds.

A Pd(OAc)2-catalyzed, AgOAc-promoted and bidentate ligand-directed Z selective C-H activation, followed by the β-arylation of the C(sp(2))-H bond of N-(quinolin-8-yl)acrylamide systems with aryl- and heteroaryl iodides, and a contemporary method for the construction of various Z-cinnamamides and β,β-diarylated acrylamides are reported. A plausible reaction mechanism comprising the bidentate ligand-aided, chelation-based C-H functionalization was proposed for the observed Z selective β-arylation of N-(quinolin-8-yl)acrylamide systems.

Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp(3) C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems.

An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp(3) C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp(3))-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities.

Direct bis-arylation of cyclobutanecarboxamide via double C-H activation: an auxiliary-aided diastereoselective Pd-catalyzed access to trisubstituted cyclobutane scaffolds having three contiguous stereocenters and an all-cis stereochemistry.

An auxiliary-aided Pd-catalyzed highly diastereoselective double C-H activation and direct bis-arylation of methylene C(sp(3))-H bonds of cyclobutanecarboxamides and the syntheses of several novel trisubstituted cyclobutanecarboxamide scaffolds having an all-cis stereochemistry are reported. Extensive screening of various auxiliaries and reaction conditions was performed to firmly establish the optimized reaction conditions required for effecting the mono- or double C-H arylation of cyclobutanecarboxamides. The auxiliary-attached cyclobutanecarboxamides 15a, 15g, and 15h, prepared from the auxiliaries such as, 8-aminoquinoline, 2-(methylthio)aniline, and N',N'-dimethylethane-1,2-diamine were found to undergo an efficient direct bis-arylation.

Auxiliary-enabled Pd-catalyzed direct arylation of methylene C(sp3)-H bond of cyclopropanes: highly diastereoselective assembling of di- and trisubstituted cyclopropanecarboxamides.

An auxiliary-enabled and Pd(OAc)2-catalyzed direct arylation of C(sp(3))-H bonds of cyclopropanes and production of di- and trisubstituted cyclopropanecarboxamides having contiguous stereocenters are reported. The installation of aryl groups on cyclopropanecarboxamides led to the assembling of novel mono- and di- aryl-N-(quinolin-8-yl)cyclopropanecarboxamide scaffolds and mono- and di- aryl-N-(2-(methylthio)phenyl)cyclopropanecarboxamides. The stereochemistry of products was unequivocally assigned from the X-ray structures of key compounds.