BBr3-mediated dearomative spirocyclization of biaryl ynones: facile access to spiro[5.5]dienones.

This report covers boron tribromide (BBr3) mediated dearomative spirocyclization of biaryl ynones. The direct synthesis of spiro[5.5]dienones with a tri-substituted double bond is described for the first time in this paper. The scope of the reaction is broad and the spirocyclic products were obtained in moderate to good yields.

Organocatalytic Asymmetric Dearomative Spirocyclization/Oxa-Michael Addition Sequence: Synthesis of Polycyclic Tetralones.

Herein, an organocatalytic asymmetric dearomative spirocyclization/oxa-Michael addition sequence with a newly designed substrate having two naphthol motifs has been developed. The reaction proceeds through in situ chiral vinylidene ortho-quinone methide (VQM) intermediate formation, dearomative spirocyclization of naphthol, and an oxa-Michael addition reaction. The densely functionalized tetralone products were formed in high yields with high diastereo- and enantioselectivities.

Organocatalytic Synthesis of Furan-Embedded Styrene Atropisomers.

Herein, we report the first synthesis of furan-embedded styrene atropisomers via the reaction between 1-(aryl-ethynyl)-naphthalen-2-ol and γ-hydroxyenone. The reaction proceeds through in situ furan formation from γ-hydroxyenone. The styrene derivatives were obtained in moderate to good yields with high diastereoselectivities with a catalytic amount of PTSA. Few applications such as triazole formation and cross-coupling reactions have been demonstrated. A preliminary catalytic asymmetric version was also reported.

Sequential organo and metal catalyzed reaction between 3-pyrrolyloxindoles and linear nitroenynes: access to cyclic aza-spirooxindoles.

An asymmetric Michael addition/hydroarylation reaction sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a combination of silver and gold salts, provides a new series of cyclic aza-spirooxindole derivatives in excellent yields (up to 94%) and high diastero- and enantioselectivities (up to 7 : 1 dr, up to >99% ee). Computational study has also been performed.

Organocatalytic Asymmetric Domino [3+2]-Cycloaddition-Acyl Transfer Reaction between Azomethine Ylides and α-Nitro-α,ß-Unsaturated Ketones.

Herein we have developed an organocatalytic asymmetric domino [3+2]-cycloaddition-acyl transfer reaction between in situ generated azomethine ylides and α-nitro-α,ß-unsaturated ketones. The desired penta-substituted pyrrolidine products were obtained in high yields and in moderate to good enantio- and diastereoselectivities. Also, an isomerization reaction in silica gel was performed for the formation of another diastereomer in high yields with retention of enantioselectivities.

Organocatalytic Asymmetric Inverse-Electron-Demand Diels-Alder Reaction between Alkylidene Pyrazolones and Allyl Ketones: Access to Tetrahydropyrano[2,3-c]pyrazoles.

Herein we report a catalytic asymmetric inverse-electron-demand Diels-Alder reaction between alkylidene pyrazolones and allyl ketones. Allyl ketone gets activated by a bifunctional thiourea catalyst and acts as a dienolate in this reaction. The trisubstituted tetrahydropyrano[2,3-c]pyrazoles were obtained in moderate to good yields with high diastereo- and enantioselectivities. Few applications, including a decarbonylation reaction, have been demonstrated.

Organocatalytic Asymmetric Synthesis of Spirooxindole Embedded Oxazolidines.

The first organocatalytic asymmetric synthesis of spirooxindole embedded oxazolidines has been developed via a domino reaction involving hemiaminal formation, followed by an unprecedented aza-Michael reaction between isatin derived N-Boc ketimines and γ-hydroxy enones. A quinine derived bifunctional squaramide catalyst was found to be efficient for this reaction, and the products were obtained in good diastereoselectivity and with high enantioselectivity.

Organocatalytic Asymmetric Addition of Aromatic α-Cyanoketones to o-Quinone Methides: Synthesis of 3,4-Dihydrocoumarins and Tetrasubstituted Chromans.

The first organocatalytic asymmetric addition of aromatic α-cyanoketones to in situ-generated o-quinone methides has been developed. The products 3,4-dihydrocoumarin and tetrasubstituted chroman were obtained via addition of aromatic α-cyanoketones to in situ-generated o-quinone methides followed by treatment with 0.7 N HCl. With 10 mol % catalyst, the desired products were obtained in high enantio- and diastereoselectivities.

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones.

An organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones is reported. A bifunctional thiourea catalyst was found to be effective for this reaction. With 10 mol % of the catalyst, good results were attained for a variety of 1,5-dihydro-2H-pyrrol-2-ones under mild reaction conditions.

DMAP Catalyzed Domino Rauhut-Currier Cyclization Reaction between Alkylidene Pyrazolones and Nitro-olefins: Access to Tetrahydropyrano[2,3-c]pyrazoles.

Herein, we employ unsaturated pyrazolones in the Rauhut-Currier reaction for the first time. A domino Rauhut-Currier cyclization reaction has been developed between unsaturated pyrazolones and nitro-olefins. The trisubstituted tetrahydropyrano[2,3-c]pyrazoles were obtained in moderate to high yields with excellent diastereoselectivities. A few applications including a synthesis of disubstituted tetrahydropyrano[2,3-c]pyrazole have been demonstrated. A preliminary catalytic asymmetric version of this process was also studied with chiral DMAP catalysts.

Organocatalytic asymmetric addition of thioglycolates to o-quinone methides: a route to 5-substituted-5H-benzoxathiepine-2(3H)-ones.

Herein we have developed the first enantioselective synthesis of 5-substituted-5H-benzoxathiepine-2(3H)-ones. 2-Sulfonylmethyl phenols and thioglycolates were employed as reaction partners in this method. The desired thia Michael products were obtained via bifunctional squaramide catalyzed conjugate addition reaction to in situ generated o-quinone methides and then basic hydrolysis followed by cyclization led to the formation of 5-substituted-5H-benzoxathiepine-2(3H)-ones. Broad scope and moderate to high enantioselectivities were observed for both products.

Organocatalytic asymmetric spirocyclization reactions of cyclic 2,4-dienones with cyanoketones: synthesis of spiro-dihydropyrano cyclohexanones.

The first organocatalytic asymmetric synthesis of spiro-dihydropyrano cyclohexanones has been developed via the cascade reaction between cyanoketones and cyclic 2,4-dienones. A cinchona alkaloid-derived bifunctional primary amine catalyst in combination with N-Boc-tleucine was found to be the most effective for this spirocyclization reaction and provided the desired products in moderate to good yields with high enantioselectivities.

DBU-Mediated Addition of α-Nitroketones to α-Cyano-enones and α,ß-Unsaturated α-Ketoesters: Synthesis of Dihydrofurans and Conjugated Dienes.

1,8-Diazabicyclo[5.4.0]undec-7-ene-mediated reactions of α-nitroketones with α-cyano-enones and α,ß-unsaturated α-ketoesters have been developed. The products, namely, dihydrofurans and conjugated dienes, were isolated in moderate to good yields, and a range of substitutions were tolerated.

Synthesis of N-Formyl-2-benzoyl Benzothiazolines, 2-Substituted Benzothiazoles, and Symmetrical Disulfides from N-Phenacylbenzothiazolium Bromides.

An unusual aerobic hydrolysis-cascade reaction has been developed with N-phenacylbenzothiazolium bromides by treatment with organic and inorganic base. The corresponding N-formyl-2-benzoyl benzothiazoline and 2-substituted benzothiazole products were obtained in moderate to good yields under mild reaction conditions. Also, symmetrical disulfide was formed when keto group was replaced with ester. The scopes of the reactions are fairly broad tolerating aryl, heteroaryl, and alkyl groups.

Organocatalytic asymmetric synthesis of dihydrofuran-spirooxindoles from benzylidene malononitriles and dioxindoles.

The first organocatalytic enantioselective synthesis of dihydrofuran-spirooxindoles having a linkage at the 2-position of the dihydrofuran motif has been developed. Dioxindoles and benzylidene malononitriles were employed in this method. The desired spirooxindole products were obtained via a Michael reaction followed by a Pinner reaction and isomerization and good to high yields with moderate diastereo and good to high enantioselectivities were observed.

Employment of α-nitroketones in organic synthesis.

α-Nitroketones, useful bidentate reagents having nitro and keto functionalities, have been recently employed in a range of metal and organocatalytic domino reactions. In fact, several C-C, C-O, and C-N bond forming reactions were developed including Michael, domino-Michael, denitration, desymmetrisation, Mannich, nucleophilic addition/elimination and cycloaddition pathways. Unlike nitroalkanes, α-nitroketones can generate a range of active 1,3 dipolar intermediates such as nitronates and nitrile oxides which have been engaged in various cycloaddition reactions. Also α-functionalisation reactions such as arylations and halogenations were carried out. A variety of useful organic frameworks such as chromans, dihydrofurans, isoxazoles, pyrazoles etc. have been prepared. This review highlights the recent developments in the utilisation of α-nitroketones in organic synthesis and discusses the progress over the current years.

Organocatalytic asymmetric Michael/hemiketalization/acyl transfer reaction of 1,3-propanediones with (E)-2-(2-nitrovinyl)phenols.

An organocatalytic asymmetric cascade Michael/hemiketalization/acyl transfer reaction between (E)-2-(2-nitrovinyl)phenols and 1,3-propanediones is disclosed. A cinchona alkaloid derived bifunctional thiourea catalyst was found to be the most effective for this reaction and provided the desired products in moderate to good yields with good to high enantioselectivities.

Organocatalytic asymmetric synthesis of highly substituted pyrrolidines bearing a stereogenic quaternary centre at the 3-position.

An organocatalytic asymmetric cascade reaction has been developed for the synthesis of highly substituted pyrrolidines having a stereogenic quaternary centre at the 3-position. N-Tosyl aminomethyl enone and trans-α-cyano-α,ß-unsaturated ketone were utilized as the reaction partners in this method. Cinchonidine derived bifunctional amino-squaramide catalysts were the best to obtain the products in high enantio- and diastereoselectivities.

Organocatalytic Asymmetric Synthesis of Bridged Acetals with Spirooxindole Skeleton.

The first highly diastereo- and enantioselective synthesis of bridged O, O-acetals embedded with spirooxindoles has been developed. Dioxindoles and 2-hydroxy cinnamaldehydes were employed as the reaction partners in this method. The desired products were obtained via diaryl prolinol TBS ether catalyzed Michael reaction followed by acetal formation with TFA.

An organocatalytic asymmetric Mannich reaction for the synthesis of 3,3-disubstituted-3,4-dihydro-2-quinolones.

The first organocatalytic asymmetric Mannich reaction employing 3,4-dihydro-2-quinolones has been developed for the synthesis of biologically important 3,3-disubstituted-dihydro-2-quinolones. N-Boc imine precursor amidosulfones as well as pre-formed N-Boc imine were used for this purpose. Cyclohexyldiamine derived bifunctional amino-thiourea catalysts were employed to provide the products in high enantio- and good diastereoselectivities.