Cobalt-catalyzed annulation of aryl iodides with alkynes

A cobalt-catalyzed approach for the concise synthesis of naphthalenes by the annulation of aryl iodides with alkynes is disclosed. In the reaction, manganese reductant and MeCN solvent are necessary to proceed efficiently, which tolerates various functional groups, for example, boronate ester. Mechanistic investigation indicates that the transformation employs electrophilic aromatic substitution (S_EAr) in the aromatic C–H bond replacement step.     

Cobalt-catalyzed reductive coupling of activated alkenes with alkynes

Cobalt complex/Zn systems effectively catalyze the reductive coupling of activated alkenes with alkynes in the presence of water to give substituted alkenes with very high regio- and stereoselectivity in excellent yields. While the intermolecular reaction of acrylates, acrylonitriles, and vinyl sulfones with alkynes takes place in the presence of CoI2(PPh3)2/Zn, the reaction of enones and enals with alkynes requires the use of the CoI2(dppe)/Zn/ZnI2 system. The intramolecular reductive coupling of activated alkenes (enones, enals, acrylates, and acrylonitriles) with alkynes also works efficiently. Further a variety of cyclic lactones and lactams were prepared using this methodology. Possible mechanistic pathways are proposed based on a deuterium-labeling experiment carried out in the presence of D2O.     

Cobalt-catalyzed regioselective carbocyclization reaction of o-iodophenyl ketones and aldehydes with alkynes, acrylates, and acrylonitrile: a facile route to indenols and indenes

An efficient cobalt-catalyzed carbocylization for the synthesis of indenols and indenes and a new method for reductive decyanation are described. 2-Iodophenyl ketones and aldehydes 1a-g undergo carbocyclization with various disubstituted alkynes 2a-k in the presence of Co(dppe)I(2) and zinc powder in acetonitrile at 80 degrees C for 3 h to afford the corresponding indenol derivatives 3a-s and4a-m in good to excellent yields. For some unsymmetrical alkynes, the carbocyclization was remarkably regioselective, affording a single regioisomer. The cobalt-catalyzed carbocyclization reaction was successfully extended to the synthesis of indene derivatives. Thus, the reaction of 2-iodophenyl ketones and aldehydes (1) with acrylates H(2)C=CHCO(2)R (7a-d) and acrylonitrile H(2)C=CHCN (7e) proceeds smoothly in the presence of Co(dppe)Cl(2)/dppe and zinc powder in acetonitrile at 80 degrees C for 24 h to afford the corresponding indenes 8a-k and 9a-c in moderate to good yields. Interestingly, when 7e was employed for the carbocylization, reductive decyanation also occurred to give an indene derivative without the cyano functionality. A possible mechanism for this cobalt-catalyzed carbocyclization reaction is also proposed.     

Direct carbocyclization of aldehydes with alkynes: combining gold catalysis with aminocatalysis

A combination of gold(I) complexes and amine bases catalyzes the 5-exo-dig cyclization of formyl alkynes. This direct alpha-functionalization of aldehydes with unactivated alkynes does not involve the use of preformed enol equivalents.     

Cobalt-catalyzed highly regio- and stereoselective intermolecular reductive coupling of alkynes with conjugated alkenes

In the presence of Co(PPh3)2I2, PPh3, water, and zinc powder, the reaction of alkynes (R1CCR2: R1 = Ph, R2 = Me (1a); R1 = Ph, R2 = Ph (1b); R1 = Et, R2 = Et (1c); R1 = Ph, R2 = (CH2)3OH (1d); R1 = CO2Et, R2 = Ph (1e); R1 = CO2Me, R2 = (CH2)4CH3 (1f); R1 = CO2Et, R2 = SiMe3 (1g)) with alkenes having an electron-withdrawing substituent (CH2=CHR: R = CO2Bu (2a), CN (2b), SO2Ph (2c) and CO2Me (2d)) proceeded smoothly in acetonitrile to give the corresponding reductive coupling products (R1HC=CR2CH2CH2R, 3a-j) in fair to excellent yields. This reductive coupling is highly regio- and stereoselective; only one isomer was observed for each reaction. The results of an isotope-labeling experiment using D2O (99%) to replace normal water for the reductive coupling of vinyl phenyl sulfone 2c with alkyne 1a revealed that the product is E-Ph(D)C=CMeCH2CH(D)SO2Ph deuterated at the olefinic proton and one of the protons of the alpha-methylene group in 84 and 96%, respectively. Possible mechanisms for this highly regio- and stereoselective ene-yne catalytic reaction are proposed.     

Cobalt-catalyzed stereoselective iodosulfonylation and diiodination of alkynes via oxidation of potassium iodide in air

Cobalt-catalyzed iodosulfonylation of alkynes can be achieved using sodium sulfinates in the presence of KI. This procedure produces numerous stereoselective (E)-β-iodoalkenyl sulfones with good yields and suppresses the formation of diiodoalkenes. Furthermore, when this reaction is performed in the absence of sodium sulfinates, the expected (E)-diiodoalkenes are obtained.     

Cobalt-catalyzed regioselective [3+2] annulation of ortho-formyl and acetyl substituted phenylboronic acids with alkynes

Treatment of alkynes with ortho-formyl and acetyl phenylboronic acids in the presence of a cobalt catalyst resulted in the formation of 2,3-disubstituted indenols in good yields. When aryl silyl alkynes were used, 2-aryl-3-silyl indenols were obtained regioselectively in good yields.     

Cobalt-catalyzed, room-temperature addition of aromatic imines to alkynes via directed C-H bond activation

A quaternary catalytic system consisting of a cobalt salt, a triarylphosphine ligand, a Grignard reagent, and pyridine has been developed for chelation-assisted C-H bond activation of an aromatic imine, followed by insertion of an unactivated internal alkyne that occurs at ambient temperature. The reaction not only tolerates potentially senstitive functional groups (e.g., Cl, Br, CN, and tertiary amide), but also displays a unique regioselectivity. Thus, the presence of substituents such as methoxy, halogen, and cyano groups at the meta-position of the imino group led to selective C-C bond formation at the more sterically hindered ortho positions. Under acidic conditions, the hydroarylation products of dialkyl- and alkylarylacetylenes underwent cyclization to afford benzofulvene derivatives, while those of diarylacetylenes afforded the corresponding ketones in moderate to good yields. A mechanistic investigation into the reaction with the aid of deuterium-labeling experiments and kinetic analysis has indicated that oxidative addition of the ortho C-H bond is the rate-limiting step of the reaction. The kinetic analysis has also shed light on the complexity of the quaternary catalytic system.     

Cobalt-catalyzed cyclotrimerization of alkynes: the answer to the puzzle of parallel reaction pathways

To understand some experimental data at odds with the computed mechanism of the CpCo(L2)-catalyzed [2 + 2 + 2] cyclotrimerization of ethyne, DFT computations were carried out following the fate of methyl- and hydroxycarbonyl-substituted alkynes to give the corresponding arenes. The key intermediate in all cases is a triplet cobaltacyclopentadiene obtained by oxidative coupling of the corresponding CpCo(bisalkyne) complex and subsequent spin change via a minimum energy crossing point (MECP). From that species, two different catalytic cycles lead to an arene product, depending on the nature of the alkyne and other ligands present: either alkyne ligation to furnish a cobaltacyclopentadiene(alkyne) intermediate or trapping by a sigma-donor ligand to generate a coordinatively saturated cobaltacyclopentadiene(PR3) complex. The former leads to the CpCo-complexed arene product via intramolecular cobalt-assisted [4 + 2] cycloaddition, whereas the latter may, in the case of a reactive dienophile (butynedioic acid), undergo direct intermolecular [4 + 2] cycloaddition to generate a cobaltanorbornene. The bridgehead cobalt atom is then reductively eliminated after another change in spin state from singlet to triplet. The necessary conditions for one or the other mechanistic pathway are elaborated.     

Intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with symmetrical and unsymmetrical alkynes

The crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon and heteroatom tethered 1,6-enynes can be accomplished with symmetrical and unsymmetrical alkynes, to afford the corresponding bicyclohexadienes in an efficient and highly selective manner.     

Rh-catalyzed [4 + 2] carbocyclization of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones and 1-naphthols

Regio-, diastereo-, and enantioselective intermolecular [4 + 2] carbocyclizations of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones and 1-naphthols have been developed by using a cationic rhodium(I)/dppb or dppp complex as a catalyst.     

Intermolecular rhodium-catalyzed [3+2+2] carbocyclization of alkenylidenecyclopropanes with activated alkynes: regio- and diastereoselective construction of cis-fused bicycloheptadienes

Polycyclic structures that contain seven-membered carbocycles constitute important structural motifs that are ubiquitous in several classes of bioactive natural products. We have developed the first regio- and diastereoselective intermolecular rhodium-catalyzed [3+2+2] carbocyclization of carbon- and heteroatom-tethered alkenylidenecyclopropanes with mono- and disubstituted alkynes for the construction of cis-fused bicycloheptadienes. This study delineates some of the critical features for controlling regioselectivity in this process and demonstrates that E-alkenes can be incorporated in a stereospecific manner to afford products with up to three new stereogenic centers. The latter feature is particularly significant given that related carbocyclization reactions are often limited in this respect.     

Ruthenium-catalyzed alkylative lactonization and carbocyclization

[reaction: see text] The cationic ruthenium complex [CpRu(NCCH3)3]PF6 promotes the coupling of monosubstituted allene carboxylic acids and simple alpha,beta-unsaturated olefins to form five- and six-membered lactones. The mild reaction conditions allow for the presence of various functional groups.     

Tandem functionalization of nonactivated alkenes and alkynes in intramolecular N-acyloxyiminium ion carbocyclization. Synthesis of 6-substituted hydroindole 2-carboxylic acids

[reaction: see text] Five-membered N-Boc acyliminium ions derived from L-pyroglutamic acid harboring 4-butenyl and 4-butynyl tethers undergo Lewis acid-mediated halo and tandem Friedel-Crafts carbocyclization within minutes at -78 degrees C to give stereodefined 6-substituted octahydroindole and hexahydroindole 2-carboxylic acid methyl esters, respectively. The cyclic vinyl bromides are excellent substrates for Pd-catalyzed Suzuki-Miyaura, Heck, and Stille couplings. The method also provides access to enantiopure sp2- and sp3-arylated azabicyclics that are novel and versatile scaffolds for chemical diversification.     

Cobalt-catalyzed cross-coupling reactions

In the last few years, we and other groups have demonstrated that economical cobalt salts can advantageously replace expensive and toxic catalysts for cross coupling reactions. These cobalt-catalyzed reactions have considerably extended the range of functionalized compounds. A variety of sensitive functional groups can be tolerated in these coupling reactions and various organic compounds RX could be involved (R = alkyl, alkynyl, aryl, allyl and X = halides: F, Cl, Br, I and even triflates). Here, we describe our contributions in this area for the preparation of a broad range of functionalized compounds from organometallic species or by direct cross-coupling.     

Light-induced carbocyclization of iodoalkenes

The direct irradiation of iodoalkenes leads to the formation of carbon-centered radical by homolysis of the C–I bond. The photoreaction is used in cyclizations with formation of six membered rings.     

Cobalt-catalyzed asymmetric olefin aziridination with diphenylphosphoryl azide

The cobalt(II) complexes of D2-symmetric chiral porphyrins, such as 3,5-Di(t)Bu-ChenPhyrin P5, can catalyze asymmetric olefin aziridination with diphenylphosphoryl azide (DPPA) as a nitrene source. Acceptable asymmetric inductions were observed for the [Co(P5)]-based catalytic system, forming the desired N-phosphorus-substituted aziridines in moderate to high yields and good enantioselectivities.