Ni-Catalyzed Diastereoconvergent Intramolecular Alkene-Aldehyde Reductive Coupling: A Route to syn-Chromanols.

We demonstrate for the first time a nickel-catalyzed diastereoconvergent reductive coupling of a heteroatom-attached allyl moiety with aldehydes, viz., O-allyl, O-cinnamyl salicylaldehydes, and others, to afford syn-chromanols exclusively. The reaction proceeds through a [2 + 2 + 1] oxidative cycloaddition involving the active catalyst. This method is applicable to both terminal and internal olefin substrates. The formal syntheses of CP-199.330, CP-199.331, and CP-85.958 have been demonstrated. Control experiments, mass spectrometric analysis, and DFT studies supported the plausible mechanism and the origin of exclusive syn-selectivity.

Cascade Aryne Aminoarylation for Biaryl Phenol Synthesis.

We describe a transition metal-free approach to hindered 3-amino-2-aryl phenols through a cascade nucleophilic addition / Smiles-Truce rearrangement of a functionalized Kobayashi aryne precursor. Under anionic conditions, secondary alkyl amines add to the aryne intermediate to set up an aryl transfer from a neighboring sulfonate group. The use of a sulfonate, rather than the more typical sulfonamide, enables access to phenolic biaryl products that are important motifs in natural products and pharmaceuticals.

Ni0-Catalyzed Regioselective [2 + 2 + 2] Cyclotrimerization of 1,3-Diynes: An Expeditious Synthesis of Hexasubstituted Alkynyl Benzenes.

In the present work, we demonstrate a regioselective [2 + 2 + 2] cyclotrimerization of 1,3-diynes catalyzed by Ni0 to provide hexasubstituted benzenes (HSBs). HSBs have significant applications as functional materials and pharmaceuticals. The present protocol exhibited remarkable versatility, transforming 1,3-diynes with diverse alkyl, aryl, and heterocyclic groups to the corresponding HSBs. With the help of control experiments and density functional theory (DFT), the mechanism of the reaction and the origin of regioselectivity were elucidated.

Benchtop nickel-catalyzed reductive coupling of aldehydes with alkynes and ynamides.

We demonstrate the potential of Ni(COD)(DQ), a bench-stable Ni0 complex, as a catalyst for the reductive coupling of aldehydes with alkynes and ynamides, providing silylated allyl alcohols with excellent yields and regioselectivities. Mass spectrometric identification of the intermediates and DFT studies supported the proposed mechanism.

Bis-benzofulvenes: Synthesis and Studies on Their Optoelectronic Properties.

We report the synthesis of bis-benzofulvenes and the studies on their optical and redox properties. Bis-benzofulvenes were achieved through the Pd-catalyzed intramolecular Heck coupling followed by Ni0-mediated C(sp2)-Br dimerization. Low optical and electrochemical energy gaps of 2.05 and 1.68 eV were achieved by tuning the substituent on the exomethylene unit and the aromatic ring. The observed trends in the energy gaps were compared, and the frontier molecular orbitals were visualized using the density functional theory.

Organophosphorus-Catalyzed Borylative Ring-Opening of Vinylcyclopropanes: A Stereoselective Route to δ-Valerolactones.

We report an operationally simple route to δ-valerolactones through an organophosphorus-catalyzed borylative ring-opening/allylation of vinylcyclopropanes providing δ-hydroxy esters stereoselectively. The δ-hydroxy esters were lactonized to obtain densely substituted δ-valerolactones. The present methodology exhibited enhanced functional group tolerance compared to the existing metal-mediated methods. A plausible mechanism for borylative ring-opening reaction has been suggested. 31P NMR studies indicated the involvement of a phosphonium zwitterionic species. The synthetic utility of the intermediate allyl boronates was demonstrated.

Strain Release of Donor-Acceptor Cyclopropyl Boronate Complexes.

The reactivity of boronate complexes which resemble donor-acceptor cyclopropanes is described. The enantioenriched cyclopropyl boronate complexes were shown to undergo concerted 1,2-metalate rearrangement/ring opening upon activation with a Lewis acid. This method provides atom-efficient access to optically active γ-carbonyl boronic esters in moderate to excellent yields with complete enantiospecificity. Furthermore, a three-component variant of the reaction was established through in situ alkylation, and the synthetic utility of the products as chiral building blocks was demonstrated.

Chiral Aniline Synthesis via Stereospecific C(sp3)-C(sp2) Coupling of Boronic Esters with Aryl Hydrazines.

An enantiospecific coupling between alkylboronic esters and lithiated aryl hydrazines is described. The reaction proceeds under transition-metal-free conditions and is promoted by acylation of a hydrazinyl arylboronate complex, which triggers a N-N bond cleavage with concomitant 1,2-metalate rearrangement. Judicious choice of the acylating agent enabled the synthesis of ortho- and para-substituted anilines with essentially complete enantiospecificity from a wide range of boronic ester substrates.

Enantiospecific sp2 -sp3 Coupling of ortho- and para-Phenols with Secondary and Tertiary Boronic Esters.

The coupling of ortho- and para-phenols with secondary and tertiary boronic esters has been explored. In the case of para-substituted phenols, after reaction of a dilithio phenolate species with a boronic ester, treatment with Ph3 BiF2 or Martin's sulfurane gave the coupled product with complete enantiospecificity. The methodology was applied to the synthesis of the broad spectrum antibacterial natural product (-)-4-(1,5-dimethylhex-4-enyl)-2-methyl phenol. For ortho-substituted phenols, initial incorporation of a benzotriazole on the phenol oxygen atom was required. Subsequent ortho-lithiation and borylation gave the coupled product, again with complete stereospecificity.

Alkynyl Moiety for Triggering 1,2-Metallate Shifts: Enantiospecific sp2 -sp3 Coupling of Boronic Esters with p-Arylacetylenes.

The enantiospecific coupling of secondary and tertiary boronic esters to aromatics has been investigated. Using p-lithiated phenylacetylenes and a range of boronic esters coupling has been achieved by the addition of N-bromosuccinimide (NBS). The alkyne functionality of the intermediate boronate complex reacts with NBS triggering the 1,2-migration of the group on boron to carbon giving a dearomatized bromoallene intermediate. At this point elimination and rearomatization occurs with neopentyl boronic esters, giving the coupled products. However, using pinacol boronic esters, the boron moiety migrates to the adjacent carbon resulting in formation of ortho boron-incorporated coupled products. The synthetic utility of the boron incorporated product has been demonstrated by orthogonal transformation of both the alkyne and boronic ester functionalities.

Direct catalytic addition of alkylnitriles to aldehydes by transition-metal/NHC complexes.

Direct catalytic addition of alkylnitriles to aldehydes allows for an atom-economical access to ß-hydroxynitriles under proton transfer conditions. Direct use of alkylnitriles as pronucleophiles has been hampered due to their low acidity resulting in an inability to generate α-cyano carbanions in a catalytic manner. A transition metal/N-heterocyclic carbene (NHC) complex prepared from [{Rh(OMe)(cod)}2] and an imidazolium-based carbene was identified as an effective catalyst to promote the reaction with as little as 1.25 mol% of catalyst loading. The corresponding Rh complex, derived from chiral triazolium salt, rendered the reaction enantioselective, albeit with moderate enantioselectivity.

Electrophile-induced C-C bond activation of vinylcyclopropanes for the synthesis of Z-alkylidenetetrahydrofurans.

We present a detailed study on the behavior of vinylcyclopropanes as masked donor-acceptor system toward the stereoselective synthesis of Z-alkylidenetetrahydrofurans. Results of bromenium catalyzed indirect activation of C-C bond of vinylcyclopropanes and concomitant cyclization to alkylidenetetrahydrofuran and other heterocycles have been discussed. The stereoselective formation of the Z-isomer is strongly controlled by the extent of destabilization of one of the gauche conformers of the vinylcyclopropane. The ring-opening/cyclization step was found to be stereospecific as in the case of DA cyclopropanes. The activation of the C-C bond leads to a tight-carbocation intermediate, which is evident from the complete retention of the stereochemistry. The retention of configuration has been established by a necessary control experiment that rules out the possibility of a double inversion pathway. The present results serve as direct stereochemical evidence in support of a tight ion-pair intermediate versus the controversial S(N)2 pathway. A 2D potential energy scan has been carried out at B3LYP/6-31G(d) level theory to obtain the relative energies of the conformers. The Z-selectivity observed has been explained on the basis of the relative population of the conformers and modeling the intermediate and transition state involved in the reaction at M06-2x/6-31+G(d) level. Energy profile for the cyclization step was modeled considering various possible pathways through which cyclization can happen. The methodology has been successfully demonstrated on vinylcyclobutanes as well.

Bromenium-catalysed tandem ring opening/cyclisation of vinylcyclopropanes and vinylcyclobutanes: a metal-free [3+2+1]/[4+2+1] cascade for the synthesis of chiral amidines and computational investigation.

We present a detailed study of a [3+2+1] cascade cyclisation of vinylcyclopropanes (VCP) catalysed by a bromenium species (Br(δ+)-X(δ-)) generated in situ, which results in the synthesis of chiral bicyclic amidines in a tandem one-pot operation. The formation of amidines involves the ring-opening of VCPs with Br-X, followed by a Ritter-type reaction with chloramine-T and a tandem cyclisation. The reaction has been further extended to vinylcyclobutane systems and involves a [4+2+1] cascade cyclisation with the same reagents. The versatility of the methodology has been demonstrated by careful choice of VCPs and VCBs to yield bicyclo[4.3.0]-, -[4.3.1]- and -[4.4.0]amidines in enantiomerically pure form. On the basis of the experimental observations and DFT calculations, a reasonable mechanism has been put forth to account for the formation of the products and the observed stereoselectivity. We propose the existence of a π-stabilised homoallylic carbocation at the cyclopropane carbon as the reason for high stereoselectivity. DFT studies at B3LYP/6-311+G** and M06-2X/6-31+G* levels of theory in gas-phase calculations suggest the ring-opening of VCP is initiated at the π-complex stage (between the double bond and Br-X). This can be clearly perceived from the solution-phase (acetonitrile) calculations using the polarisable continuum model (PCM) solvation model, from which the extent of the ring opening of VCP was found to be noticeably high. Studies also show that the formation of zero-bridge bicyclic amidines is favoured over other bridged bicyclic amidines. The energetics of competing reaction pathways is compared to explain the product selectivity.

10 years of click chemistry: synthesis and applications of ferrocene-derived triazoles.

Click chemistry has played a significant role as a rapid and versatile strategy for conjugating two molecular fragments under very mild reaction conditions. Introduction of ferrocene-derived triazole systems using click chemistry has attracted enormous interest in various fields due to its potential applications in electrochemical techniques for detection and sensing. The present discussion focuses on the synthesis of ferrocene-triazole and the importance of using a CuAAC reaction for such conjugation. Applications of ferrocene-based click reactions in conjugate chemistry, asymmetric catalysis, medicinal chemistry, host-guest interactions, and materials chemistry have been highlighted.

Tetrathiomolybdate mediated rearrangement of aziridinemethanol tosylates: a thia-aza-Payne rearrangement.

Aziridinemethanol sulfonate esters react with tetrathiomolybdate 1 to give thiirane derivatives as the major product and cyclic disulfides as minor product under mild reaction conditions via an unprecedented thia-aza-Payne-type rearrangement. Interestingly, when the reaction of 1 was carried out with 2-aziridino-cyclohexanol derivatives it resulted in the formation of thia-bicyclo[3.1.1]heptane or dithia-bicyclo[3.2.1]octane derivatives.

Direct synthesis of functionalized unsymmetrical beta-sulfonamido disulfides by tetrathiomolybdate mediated aziridine ring-opening reactions.

Direct synthesis of unsymmetrical beta-sulfonamido disulfides by ring-opening of aziridines by using benzyltriethyl-ammonium tetrathiomolybdate 1 as a sulfur transfer reagent in the presence of symmetrical disulfides as thiol equivalents has been reported. Reaction of benzyl and alkyl disulfides gave unsymmetrical beta-sulfonamido disulfides as the only product in very good yields. From the study, it has been observed that aryl disulfides containing p-NO(2), p-Cl, and p-CN led to the formation of the corresponding beta-aminosulfides as the exclusive products. However, unsubstituted aryl disulfides and the one containing electron-donating substituents (p-Me) provide a mixture of beta-sulfonamido mono- and disulfides as the products.

Conformationally locked bridged bicyclic diselenides: synthesis, structure, Se...O interaction, and theoretical studies.

A general synthetic methodology has been developed for the synthesis of a conformationally locked, bridged diselena-bicyclo[3.2.1]octane skeleton by regio- and stereospecific tandem nucleophilic ring opening of cis-1,4-aziridino-epoxides with tetraethylammonium tetraselenotungstate [Et4N]2WSe4, 1, in a one-pot synthesis. Some correlations have been made on the physicochemical characteristics of the diselenides with a change in the dihedral angles.

Regio- and stereospecific synthesis of beta-sulfonamidodisulfides and beta-sulfonamidosulfides from aziridines using tetrathiomolybdate as a sulfur transfer reagent.

A comprehensive study of a general and effective one-step procedure for the synthesis of beta-sulfonamidodisulfides directly from N-tosyl aziridines in a regio- and stereospecific manner under neutral conditions without the use of any Lewis acid or base has been reported. This methodology is extended to the synthesis of an optically pure cyclic seven-membered disulfide 29. Synthesis of a variety of beta-sulfonamidosulfides involving tandem, multistep reactions in one pot is also reported.