Intramolecular Dehydrogenative Cyclization Research Articles

Copper-Promoted Intramolecular Oxidative Dehydrogenation for Synthesizing Dihydroisocoumarins and Isocoumarins.

Isocoumarins and dihydroisocoumarins are important skeletons with a wide range of biological activities, such as anti-bacterial, anti-allergy, anti-fungal, anti-tumor, and anti-HIV properties. Herein, we demonstrated divergent syntheses of isocoumarins and 3,4-dihydroisocoumarins by intramolecular dehydrogenative cyclization of 2-(3-oxobutyl) benzoic acids. This transformation undergoes Csp3-H bonds and O-H bonds coupling in air using copper salt. The reactions may undergo free radical process.

The Benzothiazine Core as a Novel Motif for DNA-Binding Small Molecules.

A new series of 4H-1,3-benzothiazine dyes were prepared and fully characterized in an aqueous medium. Benzothiazine salts were synthesized either through the classical synthetic pathway using Buchwald-Hartwig amination or through economical and environmentally friendly electrochemical synthesis. The latest synthetic approach employs successful electrochemical intramolecular dehydrogenative cyclization of N-benzylbenzenecarbothioamides to form 4H-1,3-benzothiazines. 4H-1,3-Benzothiazines were evaluated as novel DNA/RNA probes. Through the use of several methods such as UV/vis spectrophotometric titrations, circular dichroism and thermal melting experiments, the binding of four benzothiazine-based molecules to polynucleotides was examined. Compounds 1 and 2 acted as DNA/RNA groove binders, thus suggesting the potential of these compounds as novel DNA/RNA probes. This is a proof-of-concept study and will be expanded to include SAR/QSAR studies.

Synthesis of withasomnine and pyrazole derivatives via intramolecular dehydrogenative cyclization, as well as biological evaluation of withasomnine-based scaffolds

Synthesis of a withasomnine-inspired library which shows anticancer reactivities and COX-2 inhibition via an intramolecular dehydrogenative cyclization process.

Synthesis and Photodynamics of Tetragermatetrathia[8]circulene.

Tetragermatetrathia[8]circulene has successfully been synthesized from tetraiodotetrathienylene through palladium-catalyzed germylation and rhodium-catalyzed intramolecular dehydrogenative cyclization. A single-crystal X-ray diffraction analysis elucidated that tetragermatetrathia[8]circulene has a highly symmetric, planar, and rigid structure. DFT calculations suggested that LUMO of tetragermatetrathia[8]circulene is stabilized due to σ*-π* interactions between σ* orbitals of the Ge-C bonds and π* orbitals of the thiophene rings. The excited dynamics of tetragermatetrathia[8]circulene have also been found to be significantly affected by the heavy-atom effect of the germanium atom.

Synthesis of Dibenzosiloles via Platinum-catalyzed Intramolecular Dehydrogenative Cyclization of 2-(Dialkylsilyl)biaryls

The intramolecular dehydrogenative cyclization of 2-(dialkylsilyl)biaryls proceeded in the presence of a catalytic amount of platinum(II) chloride and potassium tris(3,5-dimethyl-1-pyrazolyl)borohydride to give good yields of the corresponding dibenzosilole derivatives.

Benzosiloxaboroles: Silicon Benzoxaborole Congeners with Improved Lewis Acidity, High Diol Affinity, and Potent Bioactivity

The synthesis and physicochemical properties of benzosiloxaboroles, the silicon analogues of an important class of heterocyclic compounds—benzoxaboroles—is presented. They were prepared by halogen–lithium exchange reactions of (2-bromophenyl)boronates with n-BuLi followed by the silylation or boronation of (2-lithiophenyl)dimethylsilanes. The cyclization of the resulting 2-(dimethylsilyl)phenylboronates apparently occurs through intramolecular dehydrogenative cyclization reaction in the presence of water. Unlike the case for benzosiloxaborole, the formation of its analogue containing a thiophene ring is thermodynamically unfavorable, which was confirmed by theoretical calculations. The presence of a B–O–Si linkage results in increased Lewis acidity with respect to the analogous benzoxaboroles. The acidity is strongly enhanced by fluorination or introduction of phenyl groups at the silicon atom. Selected compounds show good antifungal activity, and thus they are potential small-molecule therapeutic agents....

Assembly of indoline-2-carboxylate-embodied dipeptides via Pd-catalyzed C(sp2)-H bond direct functionalization.

Intramolecular dehydrogenative cyclization of 2-methoxyiminoacyl-protected phenylalanine derivatives proceeded at 110 °C under catalysis of Pd(OAc)2 in the presence of 1-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate to afford substituted indoline-2-carboxylates that were converted into indoline-2-carboxylate-embodied dipeptides via Raney Ni-catalyzed hydrogenation.

Copper-catalyzed intramolecular dehydrogenative cyclization: direct access to sensitive formyl-substituted imidazo[1,2-a]pyridines

A direct method for the synthesis of formyl-substituted imidazo[1,2-a]pyridines was achieved easily from cyclization of aminopyridines and cinnamaldehydes via copper catalysis.

Copper-catalyzed diastereoselective aerobic intramolecular dehydrogenative coupling of hydrazones via sp3 C-H functionalization.

Transition metal-catalyzed cross dehydrogenative coupling is an important tool for functionalization of the α Csp3-H bond of amines. Among this reaction category, copper-catalyzed selective C-C bond formation under atmospheric O2 is of considerable research interest and significant progress has been achieved in recent years. In comparison, development of the intramolecular version of this transformation is still in its infancy. Furthermore, diastereoselective cyclization with this transformation has not been achieved. Here, we describe the highly diastereoselective intramolecular dehydrogenative cyclization of N,N-disubstituted hydrazones by a copper-catalyzed sp3 C-H bond functionalization process. The reaction protocol utilizes O2 as the oxidant and shows great functional group compatibility. Computational studies suggest that a 5-center/6-electron disrotatory cyclization mechanism is probably involved in the process for controlling the diastereoselectivity. This work represents the first example of a copper-catalyzed, direct intramolecular diastereoselective coupling reaction via an iminium ion intermediate. Additionally, it provides an environmentally friendly and atom efficient approach to access substituted pyrazolines, an important structural unit in many biologically active compounds.

Nickel-catalyzed site-selective amidation of unactivated C(sp(3))-H bonds.

Intramolecular dehydrogenative cyclization of aliphatic amides was achieved on unactivated sp(3) carbon atoms by a nickel-catalyzed CH bond functionalization process with the assistance of a bidentate directing group. The reaction favors the CH bonds of β-methyl groups over the γ-methyl or β-methylene groups. Additionally, a predominant preference for the β-methyl CH bonds over the aromatic sp(2) CH bonds was observed. Moreover, this process also allows for the effective functionalization of benzylic secondary sp(3) CH bonds.

Copper-Catalyzed Intramolecular N–S Bond Formation by Oxidative Dehydrogenative Cyclization

Copper-catalyzed synthesis of benzo[d]isothiazol-3(2H)-ones and N-acyl-benzothiazetidine by intramolecular dehydrogenative cyclization is described. In this reaction, a new nitrogen-sulfur (N-S) bond is formed by N-H/S-H coupling. The present reaction has high functional group tolerance and gives products in gram scale. This method promotes double cyclization, allowing for synthesis of a drug intermediate.

Copper‐Catalyzed Aerobic Intramolecular Dehydrogenative Cyclization of N,N‐Disubstituted Hydrazones through CH Functionalization

Copper‐Catalyzed Aerobic Intramolecular Dehydrogenative Cyclization of N,N‐Disubstituted Hydrazones through CH Functionalization

Copper‐Catalyzed Aerobic Intramolecular Dehydrogenative Cyclization of N,N‐Disubstituted Hydrazones through CH Functionalization

An aerobic activity: The title reaction proceeds through an oxidation/cyclization/aromatization sequence under an atmosphere of O(2) (see scheme; DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, DCE=1,2-dichloroethane, DMS=dimethylsulfide). This coupling reaction is the first to proceed via an iminium intermediate for a C(sp(3)-H bond-functionalization process, and provides an environmentally friendly and atom-efficient access to substituted pyrazoles.

ChemInform Abstract: Copper‐Catalyzed Aerobic Dehydrogenative Cyclization of N‐Methyl‐N‐phenylhydrazones: Synthesis of Cinnolines.

AbstractN‐Phenylhydrazones as novel substrates for copper‐catalyzed aerobic intramolecular dehydrogenative cyclization are presented.

Correction to Palladium-Catalyzed Synthesis of Dibenzophosphole Oxides via Intramolecular Dehydrogenative Cyclization

Correction to Palladium-Catalyzed Synthesis of Dibenzophosphole Oxides via Intramolecular Dehydrogenative Cyclization

Copper‐Catalyzed Aerobic Dehydrogenative Cyclization of N‐Methyl‐N‐phenylhydrazones: Synthesis of Cinnolines

N-Phenylhydrazones as novel substrates for copper-catalyzed aerobic intramolecular dehydrogenative cyclization are presented.

Copper‐Catalyzed Aerobic Dehydrogenative Cyclization of N‐Methyl‐N‐phenylhydrazones: Synthesis of Cinnolines

N-Phenylhydrazones as novel substrates for copper-catalyzed aerobic intramolecular dehydrogenative cyclization are presented.

ChemInform Abstract: Palladium‐Catalyzed Synthesis of Dibenzophosphole Oxides via Intramolecular Dehydrogenative Cyclization.

ChemInformVolume 43, Issue 4 Organoelement Compounds ChemInform Abstract: Palladium-Catalyzed Synthesis of Dibenzophosphole Oxides via Intramolecular Dehydrogenative Cyclization. Yoichiro Kuninobu, Yoichiro Kuninobu Div. Chem. Biochem., Grad. Sch. Nat. Sci. Technol., Okayama Univ., Okayama 700, JapanSearch for more papers by this authorTakuya Yoshida, Takuya Yoshida Div. Chem. Biochem., Grad. Sch. Nat. Sci. Technol., Okayama Univ., Okayama 700, JapanSearch for more papers by this authorKazuhiko Takai, Kazuhiko Takai Div. Chem. Biochem., Grad. Sch. Nat. Sci. Technol., Okayama Univ., Okayama 700, JapanSearch for more papers by this author Yoichiro Kuninobu, Yoichiro Kuninobu Div. Chem. Biochem., Grad. Sch. Nat. Sci. Technol., Okayama Univ., Okayama 700, JapanSearch for more papers by this authorTakuya Yoshida, Takuya Yoshida Div. Chem. Biochem., Grad. Sch. Nat. Sci. Technol., Okayama Univ., Okayama 700, JapanSearch for more papers by this authorKazuhiko Takai, Kazuhiko Takai Div. Chem. Biochem., Grad. Sch. Nat. Sci. Technol., Okayama Univ., Okayama 700, JapanSearch for more papers by this author First published: 29 December 2011 https://doi.org/10.1002/chin.201204162Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume43, Issue4January 24, 2012 RelatedInformation

Palladium-Catalyzed Synthesis of Dibenzophosphole Oxides via Intramolecular Dehydrogenative Cyclization

Dibenzophosphole oxides were obtained from secondary hydrophosphine oxides with a biphenyl group by dehydrogenation via phosphine-hydrogen and carbon-hydrogen bond cleavage in the presence of a catalytic amount of palladium(II) acetate, Pd(OAc)(2). By using this reaction, a ladder-type dibenzophosphole oxide could also be synthesized by double intramolecular dehydrogenative cyclization.

Reaction of 1-(Dimethylsilyl)-2-silylbenzene with Platinum(0) Phosphine Complexes

Reaction of 1,2-C6H4(SiMe2H)(SiH3) (8) with Pt(dmpe)(PEt3)2 (dmpe = Me2PCH2CH2PMe2) or Pt(dmpe)2 in 1:1 ratio at room temperature gave {1,2-C6H4(SiMe2)(SiH2)}PtII(dmpe) (11a) as a major product in solution. Complex 11a can easily dimerize to form [(dmpe)PtIV(H){1,2-C6H4(SiMe2)(μ-SiH)}]2 (12a), and 11a and 12a are in equilibrium in solution. Although monomer 11a is a major species in solution, only dimer 12a crystallized out from toluene, THF, or DMF solution. Addition of excess dmpe to a toluene solution of 11a/12a trapped the PtII species as a pentacoordinated dimer [{1,2-C6H4(SiMe2)(SiH2)}PtII(dmpe)]2(μ-dmpe) (13). A similar reaction took place between 8 and Pt(depe)(PEt3)2 (depe = Et2PCH2CH2PEt2) or Pt(depe)2 to give {1,2-C6H4(SiMe2)(SiH2)}PtII(depe) (11b) and [(depe)PtIV(H){1,2-C6H4(SiMe2)(μ-SiH)}]2 (12b), and 11b and 12b are in equilibrium in solution. Two equivalents of 8 reacted with Pt(dmpe)(PEt3)2 in toluene at room temperature to afford two isomeric {1,2-C6H4(SiMe2H)(SiH2)}{1,2-C6H4(SiMe2)(SiH2)}(H)PtIV(dmpe) complexes 16 and 17 in 5:3 ratio among eight possible isomers. Heating the mixture of 16 and 17 at 100 °C in toluene resulted in slow intramolecular dehydrogenative cyclization to afford a mixture of isomeric {1,2-C6H4(SiMe2)(SiH2)}2PtIV(dmpe) 18 and 19. The structures of complexes 12a, 12b, 13, 17, 18, and 19 were unambiguously determined by single-crystal X-ray analysis.