Dehydrogenative [4 + 2] cycloaddition of formamides with alkynes through double C-H activation

Formamides having 1-arylalkyl groups on nitrogen undergo an unprecedented dehydrogenative [4 + 2] cycloaddition reaction with alkynes via nickel/AlMe(3) cooperative catalysis to give highly substituted dihydropyridone derivatives in good yields. Notably, the transformation proceeds through double functionalization of C(sp(2))-H and C(sp(3))-H bonds in the formamides.     

Cobalt-mediated [2+2+2] cycloaddition versus C-H and N-H activation of pyridones and pyrazinones with alkynes: an experimental study

The reactivity of a range of pyridone and pyrazinone derivatives towards alkynes in the presence of cyclopentadienylcobaltbis(ethene) has been investigated. Depending on the nature of the substrates, [2+2+2]- or [2+2] cycloaddition, C-H, or N-H activation may occur. In the case of pyridones, the first three predominated with N-protected derivatives, whereas substrates containing N-H bonds followed an N-H activation pathway. The [2+2+2] cycloaddition of an N-butynylisoquinolone was applied successfully to the total synthesis of anhydrolycorinone. Pyrazinone substrates showed similar patterns of reactivity.     

Cobalt-mediated [2+2+2] cycloaddition versus C-H and N-H activation of 2-pyridones and pyrazinones with alkynes: a theoretical study

DFT computations have been executed aimed at illuminating the variety of pathways by which pyridones react with alkynes in the presence of [CpCoL(2)]: NH-2-pyridones furnish N-dienylated ligands (N-H activation pathway), N-methyl-2-pyridones are converted into ligated cyclohexadienes ([2+2+2] cocycloaddition pathway), and N-alkynyl-2-pyridones may undergo either [2+2+2] cocycloaddition or C-dienylation (C-H activation), depending on the length of the tether. The calculations predict the formation of the experimentally observed products, including their regio- and stereochemical make up. In addition, the unusual regiochemical outcome of the all-intramolecular [2+2+2] cycloaddition of N,N'-dipentynylpyrazinedione was rationalized by computation, which led to the discovery of a new mechanism.     

Highly regioselective [2+2+2] cycloaddition of terminal alkynes catalyzed by titanium complexes of p-tert-butylthiacalix[4]arene

Mono- and dinuclear titanium complexes of p-tert-butylthiacalix[4]arene were applied as a catalyst for [2+2+2] cycloaddition of terminal alkynes. They showed high catalytic activity and regioselectivity toward 1,3,5-trisubstituted benzenes over 1,2,4-trisubstituted isomers. The regioselectivity was rationalized in terms of the steric effect of the thiacalixarene skeleton and the coordination of the bridging sulfur atom to the titanium center.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Nickel-mediated regioselective [2 + 2 + 2] cycloaddition of carboryne with alkynes

Transition metal-benzyne complexes have found many applications in organic synthesis, mechanistic studies, and the synthesis of functional materials. In sharp contrast, the chemistry of transition metal-carboryne complexes, especially late transition metal complexes, is virtually unknown. This communication reports a novel nickel-mediated regioselective [2 + 2 + 2] cycloaddition reaction of carboryne with alkynes via the Ni-carboryne intermediate (eta2-C2B10H10)Ni(PPh3)2. Because of the bulkiness of the carborane moiety, a high regioselectivity was achieved in the reactions involving unsymmetrical alkynes. This work furnishes a novel method for the preparation of highly substituted benzocarboranes which are difficult to obtain by other methods.     

Rhodium-catalyzed [2 + 2 + 2] cycloaddition of alkenyl isocyanates and alkynes

A rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition between alkenyl isocyanates and alkynes has been developed. Heating a mixture of an alkenyl isocyanate and a symmetrical internal alkyne in the presence of [Rh(ethylene)2Cl]2/P(4-OMe-C6H4)3 in toluene delivers substituted indolizinones and quinolizinones. Depending on the substrates, a rare fragmentation of the isocyanate unit can be involved within the cycloaddition process to furnish a vinylogous amide embedded in the indolizinone.     

Microwave-assisted iridium-catalyzed [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes

The [Ir(COD)Cl]₂/dppe system effectively catalyzes the solid-phase [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes under microwave conditions. The reaction results in high purity of isoindoline derivatives with moderate yields.     

Nickel-catalyzed chelation-assisted transformations involving ortho C-H bond activation: regioselective oxidative cycloaddition of aromatic amides to alkynes

Although the pioneering example of ortho metalation involving cleavage of C-H bonds was achieved using a nickel complex (Kleiman, J. P.; Dubeck, M. J. Am. Chem. Soc. 1963, 85, 1544), no examples of catalysis using nickel complexes have been reported. In this work, the Ni-catalyzed transformation of ortho C-H bonds utilizing chelation assistance, such as oxidative cycloaddition of aromatic amides with alkynes, has been achieved.     

NbCl3-catalyzed three-component [2 + 2 + 2] cycloaddition reaction of terminal alkynes, internal alkynes, and alkenes to 1,3,4,5-tetrasubstituted 1,3-cyclohexadienes

Three-component [2 + 2 + 2] cycloaddition of terminal alkynes, internal alkynes, and terminal alkenes is achieved using an NbCl(3)(DME) catalyst, leading to 1,3,4,5-substituted 1,3-cyclohexadienes in excellent yields with high chemo- and regioselectivity.     

C-C versus C-H bond activation of alkynes by early second-row transition metal atoms

The reactions of Y (a2D), Zr (a3F), Nb (a6D), Mo (a7S), and electronically excited-state Mo* (a5S) with propyne (methylacetylene) and 2-butyne (1,2-dimethylacetylene) were investigated using crossed molecular beams. For all of the metals studied, reactions with propyne led to H2 elimination, forming MC3H2. For Y + propyne, C-C bond cleavage forming YCCH + CH3 also was observed, with an energetic threshold in good agreement with an earlier determination of D0(Y-CCH). For Y + 2-butyne, three reactive channels were observed: YC4H4 + H2, YC3H3 + CH3, and YC3H2 + CH4. The C-C bond cleavage products accounted for 21 and 27% of the total products at Ecoll = 69 and 116 kJ/mol, respectively. For Zr and Nb reactions with 2-butyne, competition between H2 and CH4 elimination was observed, with C-C bond cleavage accounting for 12 and 4% of the total product signal at Ecoll = 71 kJ/mol, respectively. For reactions of Mo and Mo* with 2-butyne, only H2 elimination was observed. The similarity between reactions involving two isomeric species, propyne and allene, suggests that H atom migration is facile in these systems.     

Catalytic enantioselective intermolecular [2 + 2 + 2] cycloaddition of an alkene and two alkynes

A catalytic enantioselective intermolecular [2 + 2 + 2] cycloaddition of one molecule of alkene (enone) and two molecules of alkyne was developed in the presence of a nickel complex modified by chiral monodentate oxazoline ligands, which have not previously been used as chiral ligands for transition metals in asymmetric catalysts, and an aluminium phenoxide.     

C-H activation of terminal alkynes by tris-(3,5-dimethylpyrazolyl)boraterhodiumneopentylisocyanide: new metal-carbon bond strengths

C-H bond activation of terminal alkynes by [Tp'Rh(CNneopentyl)] (Tp' = hydridotris-(3,5-dimethylpyrazolyl)borate) resulted in the formation of terminal C-H bond activation products Tp'Rh(CNneopentyl)(C≡CR)H (R = t-Bu, SiMe(3), hexyl, CF(3), p-MeOC(6)H(4), Ph, and p-CF(3)C(6)H(4)). A combination of kinetic selectivity determined in competition reactions and activation energy for reductive elimination has allowed for the calculation of relative Rh-C(alkynyl) bond strengths. The bond strengths of Rh-C(alkynyl) products are noticeably higher than those of Rh-C(aryl) and Rh-C(alkyl) analogues. The relationship between M-C and C-H bond strengths showed a linear correlation (slope R(M-C/H-C) = 1.32), and follows energy correlations previously established for unsubstituted sp(2) and sp(3) C-H bonds in aliphatic and aromatic hydrocarbons.     

Enantioselective synthesis of indolizidines bearing quaternary substituted stereocenters via rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and terminal alkynes

An enantioselective synthesis of indolizidines bearing quaternary substituted stereocenters by way of a rhodium-catalyzed [2+2+2] cycloaddition of substituted alkenyl isocyanates and terminal alkynes is described. The reaction provides lactam products using aliphatic alkynes, whereas aryl alkynes give rise to vinylogous amide products. Through modification of the phosphoramidite ligand, high levels of enantioselectivity, regioselectivity, and product selectivity are obtained for both products.     

[4+2]cycloaddition reactions of triarylphosphaalkene

Cycloaddition reactions of mesityl(diphenyliiifithylene)phosphine ($\text{1}$) were Investigated. With several dienes, no Diels-Alder reactions were oEserved. With azides, diphenyidiazomethane and 2,4,6-trimethylbenzonitrile oxide, the corresponding cycloadducts ($\text{4}$$\text{12}$$\text{17}$$\text{12}$were obtained. In the case of phenyl azide, a competing Staudinger reaction occurred leading to $\text{3}$.     

Enantioselective rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and terminal alkynes: application to the total synthesis of (+)-lasubine II

The use of TADDOL-based phosphoramidite ligands on rhodium allows for the incorporation of terminal alkynes in the [2+2+2] cycloaddition with alkenyl isocyanates. Terminal aliphatic alkynes provide bicyclic lactams, while the use of aryl alkynes provides complementary access to vinylogous amides. Product selectivity seems to be governed by a combination of electronics and sterics, with smaller and/or more electron-deficient substituents favoring lactam formation. The use of homologous alkenyl isocyanates leads to an expedient asymmetric total synthesis of the alkaloid lasubine II.     

Synthesis of silafluorenes by iridium-catalyzed [2 + 2 + 2] cycloaddition of silicon-bridged diynes with alkynes

[reaction: see text] Silicon-bridged 1,6-diynes underwent [2 + 2 + 2] cycloaddition with alkynes in the presence of an iridium(I)-phosphine catalyst to afford densely substituted silafluorene derivatives. Extended silafluorene skeletons were constructed by the [2 + 2 + 2] cycloaddition of tetraynes.     

Generation of 4-polyfluoroaryl pyrrolo[1,2-a]quinolines via C-H bond activation

A novel and efficient preparation of 4-polyfluoroaryl pyrrolo[1,2-a]quinolines via a palladium-catalyzed reaction of 1-[2-(2,2-dibromoethenyl)phenyl]-1H-pyrrole with polyfluoroarene is described. This transformation is efficient, leading to the corresponding products in good yields.