Annulative Coupling Research Articles

Synthesis of Indenones through Rhodium(III)-catalyzed [3+2] Annulation Utilizing a Recyclable Carbazolyl Leaving Group

Abstract The rhodium(III)-catalyzed annulative coupling of 9-benzoylcarbazoles with internal alkynes proceeds efficiently through ortho C–H and C–N bond cleavages. This reaction provides direct access to variously substituted indanone derivatives. The carbazolyl leaving group can be readily recovered and reused for preparing the starting materials.

Synthesis of Substituted Indene Derivatives via Silver-catalyzed Annulative 1:1 Coupling of Secondary Benzyl Alcohols with Alkynes

The annulative coupling of secondary benzyl alcohols with internal alkynes efficiently proceeds in the presence of a silver catalyst. The reaction gives 1,2,3-substituted indene derivatives selecti...

Formal synthesis of schulzeines B and C: A new route to Gurjar's lactams

AbstractDescribed is a formal synthesis of racemic schulzeines B and C that intercepts intermediates developed by Gurjar and co‐workers. The synthetic sequence features an annulative coupling of a ketimine and acrylic acid enabling the construction of the benzoquinolizidine nucleus in a highly convergent manner. We also examined a continuous‐flow version of the thermal aza‐annulation, which proved less practical as compared to the batch processes.

Creation of negatively curved polyaromatics enabled by annulative coupling that forms an eight-membered ring

The discoveries of new forms of carbon have always opened doors to new science and technology. In 1991, three-dimensional (3D) periodic carbon crystals with negative Gaussian curvatures that consist of six- and eight-membered rings were proposed. To realize these 3D periodic carbon crystals (known as Mackay crystals), methods for creating polyaromatic structures embedding eight-membered rings must be developed. Here we report two annulative coupling reactions that form an eight-membered ring through catalytic C–H functionalization. We have discovered that bay-chlorinated polyaromatics undergo either annulative dimerization or cross-coupling with biphenylene in the presence of a palladium catalyst to form various hitherto inaccessible polyaromatics embedding an eight-membered ring. The threefold annulative cross-coupling of 1,5,9-trichlorotriphenylene allowed construction of a highly curved nanocarbon. The present work not only demonstrates the potential of annulative coupling for constructing octagonal nanocarbons but also provides a conceptual pathway for the synthetic realization of 3D periodic carbon crystals. The Mackay crystal is a proposed—but synthetically unachieved—nanocarbon molecule that is anticipated to have many desirable properties. Now, a strategy based on annulative coupling of chlorophenanthrene derivatives is reported, allowing streamlined access to an important substructure.

Rhodium(II)-Catalyzed Annulative Coupling of β-Ketothioamides with α-Diazo Compounds: Access to Highly Functionalized Thiazolidin-4-ones and Thiazolines.

An operationally simple and efficient one-pot protocol for the synthesis of highly functionalized thiazolidin-4-ones and thiazolines has been devised via Rh(OAc)2-catalyzed annulative coupling of β-ketothioamides with diazo compounds under mild reaction conditions for the first time. This double functionalization of diazo compounds proceeds via selective S-alkylation followed by intramolecular N-cyclization enabling the formation of C-S and C-N bonds at moderate temperature. Notably, the products possess Z-stereochemistry with regard to the exocyclic C═C double bond at the 2-position of the ring. Further, the synthetic utility of the strategy has been revealed to access 2,3-dihydrobenzo[d]thiazoles. Remarkably, atom economy and tolerance of a wide range of functional groups are added characteristics to this strategy.

Transition-Metal-Catalyzed Annulative Coupling Cascade for the Synthesis of 3-Methyleneisoindolin-1-ones

This short review describes the recent progress made on transition-metal-catalyzed annulative couplings for the synthesis of 3-methyleneisoindolin-1-ones, which are useful intermediates for the synthesis of numerous alkaloids and can be often found in a wide range of natural products and pharmaceuticals. In particular, new one-pot multiple C–C/C–N bond-forming processes for the construction of the 5-methylenepyrrol-2-one nucleus of such compounds are summarized.1 Introduction2 Intramolecular Cyclization Reactions: C3–N or C3–C3a and C–C Bond Formation3 Intermolecular Annulative Coupling Reactions3.1 C3–C3a and C3–N Bond Formation3.2 C1–C7a and C3–N Bond Formation3.3 C1–C7a and C1–N Bond Formation3.4 C1–C7a, C1–N and C3–N Bond Formation3.5 C3–C3a, C1–C7a, C1–N and C3–N Bond Formation: A Pd-Catalyzed One-Pot Sonogashira Coupling–Carbonylation–Amination–Cyclization Cascade4 Conclusion

Rhodium-Catalyzed Annulative Coupling of Isothiazoles with Alkynes through N–S Bond Cleavage

A Rh(III)-catalyzed annulative coupling of 3,5-diarylisothiazoles and alkynes is reported. The N-S bond in the isothiazole ring acts as an internal oxidant to regenerate the Rh(III) species in combination with an external Cu(II) oxidant, and the corresponding 1:2 coupling products are obtained. The remarkable difference in the reaction outcome between isothiazoles and the relevant isoxazoles has been investigated by DFT calculations, revealing that the relative stability of the enolate intermediates dictates the product selectivity.

Copper-Catalyzed Annulative Coupling of S,S-Disubstituted Enones with Diazo Compounds to Access Highly Functionalized Thiophene Derivatives.

An efficient protocol toward fully substituted thiophenes and thieno[2,3-b]thiophenes has been developed through CuCl2-catalyzed annulative coupling of S,S-disubstituted enones with diazo compounds under mild conditions. Tetrasubstituted thiophenes and thieno[2,3-b]thiophenes were efficiently accessed by variation of the feed ratio of the reactants in good to excellent yields, respectively. The synthetic methodology has demonstrated the potential for the construction of diverse thiophene derivatives.

Mechanistic insight into the rhodium(III)‐catalyzed ortho‐selective coupling of diverse arenes with 4‐acyl‐1‐sulfonyltriazoles: A computational study

AbstractA mechanistic study of the Cp*Rh(III)‐catalyzed annulative coupling of benzimidates with 4‐acyl‐1‐sulfonyltriazoles by CH activation was performed using density functional M06 method. It was demonstrated that the active catalyst during the coupling process should be the cation [Cp*Rh(OAc)]+ rather than the neutral Cp*Rh(OAc)2 and Zn(OAc)2 as proposed previously by the experimenters. A novel energetically feasible reaction pathway has been revealed theoretically in details. The acetic acid‐mediated cyclization process was confirmed to be the rate‐limiting step with an overall barrier of 24.3 kcal/mol, excluding any importance of the CH cleavage mechanism as supported by the kinetic isotope effect experiments. The major factors responsible for the preferred regioselectivity of N‐pyrimidinylinoles with 4‐acetyl‐1‐sulfonyltriazoles were discussed.

Rhodium-Catalyzed Annulative Coupling Using Vinylene Carbonate as an Oxidizing Acetylene Surrogate

Transition-metal-catalyzed C–H activation and subsequent oxidative cyclization with alkynes has been a powerful tool for the synthesis of polycyclic aromatic compounds. Despite the substantial prog...

Rhodium(III)-Catalyzed Annulative Coupling of Sulfoxonium Ylides and Allenoates: An Arene C-H Activation/Cyclopropanation Cascade.

Rhodium(III)-catalyzed annulative coupling of sulfoxonium ylides with allenoates was achieved, forming highly functionalized cyclopropanes with a quaternary carbon center by means of the sulfoxonium ylide functionality as a traceless bifunctional directing group and C4 synthon via an arene C-H activation and cyclopropanation cascade. The protocol features simultaneous formation of three new C-C bonds in one pot with excellent diastereoselectivity. The resultant cyclopropanation products could be further transformed to diverse synthetically useful compounds.

Synthesis of 2-Arylindoles by Rhodium-Catalyzed/Copper-Mediated Annulative Coupling of N-Aryl-2-aminopyridines and Propargyl Alcohols via Selective C-H/C-C Activation.

A versatile rhodium-catalyzed/copper-mediated C-H/C-C activation and cascade annulation reaction was described to form 2-arylindole derivatives. Highly selective C-C bond cleavage of γ-substituted tert-propargyl alcohols occurred, together with pyridine-directed ortho C(sp2)-H bond activation, affording a series of 2-arylindoles with yields up to 90%. Subsequent derivations were smoothly conducted to access polyfunctionalized 2-arylindoles, illustrating the potential applications of this method.

Visible-Light-Promoted Three-Component Coupling Annulation: Synthesis of 2-Iminothiazolidin-4-ones via in Situ Formed Electron Donor-Acceptor Complexes.

A novel and efficient three-component coupling annulation strategy for the synthesis of 2-iminothiazolidin-4-ones from amines, isothiocyanates, and alkyl acetylenedicarboxylates under visible-light irradiation conditions has been demonstrated. In this transformation, the in situ formed photoactive electron donor-acceptor (EDA) complexes facilitate the reaction and smoothly generate the corresponding products with a high adaptability under mild conditions. This protocol provides a cost-efficient and practical route to 2-iminothiazolidin-4-ones and promotes potential applications on the synthetic drugs.

Pd-Catalyzed Three-Component Domino Reaction of Vinyl Benzoxazinanones for Regioselective and Stereoselective Synthesis of Allylic Sulfone-Containing Amino Acid Derivatives.

A Pd-catalyzed, highly regioselective and stereoselective three-component domino allylic substitution/N-H carbene insertion reaction under mild conditions is described. This reaction demonstrates a wide substrate scope and satisfactory functional group tolerance, providing a broad range of allylic sulfone-containing amino acid derivatives. Moreover, DBU mediates highly diastereoselective cross-dehydrogenative coupling annulation of allylic sulfones without using peroxides or any metal oxidants. This developed protocol affords 7-membered ring heterocyclic compounds incorporating both sulfone-containing amino acid esters and one quaternary carbon center. Mechanistic studies indicate that an unusual umpolung of glycine occurred in this annulation.

Rhodium-Catalyzed Cascade Annulative Coupling of 3,5-Diarylisoxazoles with Alkynes

A rhodium-catalyzed cascade annulative coupling of 3,5-di­arylisoxazoles with three equivalents of an alkyne proceeds smoothly in the presence of a Cu(II) oxidant, where the sequential construction of isoquinoline and naphtho[1,8-bc]pyran frameworks connected by a biaryl linkage is achieved by a single operation. Most of the obtained polycyclic compounds exhibit visible fluorescence in both the solution and the solid state. The hexaphenylated isoquinoline-naphthopyran conjugate (R = Ph) as a representative product shows a green emission which can be turned off by making an isoquinolinium salt with an acid. The emission is also reversibly turned on by treatment with a base.

Divergent Annulative C–C Coupling of Indoles Initiated by Manganese-Catalyzed C–H Activation

Manganese(I)-catalyzed C–H activation of indoles and divergent annulative coupling with alkyne-tethered cyclohexadienones has been realized under operationally simple conditions. These annulation systems are under condition control. The coupling in the presence of BPh3 additive followed a C–H activation-alkyne insertion-Michael addition pathway, affording an exocyclic olefin attached to a tetrahydrofuran ring. In contrast, when Zn(OAc)2/PivOH additives were introduced, initial olefination en route to intramolecular Diels–Alder reaction and subsequent elimination of an alcohol was followed to deliver a fused six-membered ring. The selectivity stands in contrast to those reported using rhodium(III) and cobalt(III) catalysts, highlighting the unique reactivity and selectivity of manganese catalysts.

RuII‐Catalyzed Annulative Coupling of Benzoic Acids with Vinyl Sulfone via Weak Carboxylate‐Assisted C−H Bond Activation

AbstractAn efficient annulative coupling of benzoic acids with vinyl sulfone is developed based on weak carboxylate‐assisted RuII‐catalyzed ortho C−H bond activation, delivering sulfone containing phthalides in high yields (up to 92 %). The protocol features operational simplicity, mild conditions, and broad substrate scope with wide functional groups tolerance. The synthetic utility was highlighted through the preparation of biologically relevant 3‐ylidenephthalide scaffolds. This work represents the first example of RuII‐catalyzed annulation of benzoic acid with aryl vinyl sulfone.

Synthesis of Substituted Helicenes by Ir-Catalyzed Annulative Coupling of Biarylcarboxylic Acid Chlorides with Alkynes

Abstract A series of substituted [4] and [5]helicenes were synthesized in moderate to good yields by an Ir-catalyzed annulative coupling of biarylcarboxylic acid chlorides with internal alkynes, which involves facile C-H bond cleavage and decarbonylation. The double annulative coupling of 1,1′:5′,1′′-ternaphthalene-2,2′′-dicarboxylic acid dichloride with 4-octyne was also accomplished to give rise to an S-shaped double helicene. Unexpectedly, a π-extended benzofluoranthene-merged [5]helicene was constructed through the annulative coupling and the successive C(aryl)-C(aryl) bond forming reaction when 1,1′:4′,1′′-ternaphthalene-2,2′′-dicarboxylic acid dichloride was employed as the substrate. The crystal structure and the optical properties of the latter unique product were also investigated.

Access to Quaternary Stereogenic Centers via Rhodium(III)-Catalyzed Annulations between 2-Phenylindoles and Ketenes.

Rh(III)-catalyzed C-H activation of arenes and mild oxidative [4 + 2] annulative coupling with ketenes have been realized. The uniquely high reactivity of the C(3) of 2-phenylindoles was successfully utilized to facilitate the reductive elimination process, leading to efficient synthesis of cyclic products with a quaternary carbon stereocenter.

Rhodium(iii)-catalyzed annulative coupling between arenes and sulfoxonium ylides via C–H activation

Sulfoxonium ylides acts as a bifunctional C2-synthon in Rh(iii)-catalyzed redox-neutral annulative coupling with arenes for the synthesis of N-heterocycles and carbocycles.