Three characteristic reactions of alkynes with metal compounds in organic synthesis

Alkynes have two sets of mutually orthogonal π‐bonds that are different from the π‐bonds of alkenes. These π‐bonds are able to bond with transition metal compounds. Alkynes easily bond with the various kinds of compounds having a π‐bond such as carbon monoxide, alkenes, other alkynes and nitriles in the presence of the transition metal compounds. The most representative reaction of alkynes is called the Pauson–Khand reaction. The Pauson–Khand reactions include the cyclization of alkynes with alkenes and carbon monoxide in the presence of cobalt carbonyls. Similar Pauson–Khand reactions also proceed in the presence of other transition metal compounds. These reactions are the first type of characteristic reaction of alkynes. Other various kinds of cyclizations with alkynes also proceed in the presence of the transition metal compounds. These reactions are the second type of characteristic reaction of alkynes. These include cyclooligomerizations and cycloadditions. The cyclooligomerizations include mainly cyclotrimerizations and cyclotetramerizations, and the cycloadditions are [2 + 2], [2 + 2 + 1], [2 + 2 + 2], [3 + 2], [4 + 2], etc., type cycloadditions. Alkynes are fairly reactive because of the high s character of their σ‐bonds. Therefore, simple coupling reactions with alkynes also proceed besides the cyclizations. The coupling reactions are the third type of characteristic reactions of alkynes in the presence of, mainly, the transition metal compounds. These reactions include carbonylations, dioxycarbonylations, Sonogashira reactions, coupling reactions with aldehydes, ketones, alkynes, alkenes and allyl compounds. Copyright © 2008 John Wiley & Sons, Ltd.     

Competition between alkenes in intramolecular ketene-alkene [2 + 2] cycloaddition: what does it take to win?

In the course of developing a new synthetic methodology using ketenes in sequential cycloaddition steps, we were faced with a competition problem with molecules containing a ketene tethered to more than one reacting partner. To pinpoint the electronic and tethering requirements for a chemoselective reaction, we undertook a series of ketene-alkene [2 + 2] cycloaddition competition experiments. Those experiments were conducted on molecules containing either two identical alkenes having different tether lengths or two alkenes having the same tether length but being electronically different. We demonstrated that the reaction is much faster for forming five-membered rings than six-membered rings and calculated the Hammett constant rho for intramolecular ketene-alkene [2 + 2] cycloadditions to be -1.39.     

Tf2NH-catalyzed,highly regio-and stereo-selective synthesis of trisubstituted alkenes and indane derivatives from benzylic alcohols and alkenes

A reaction of benzylic alcohols with alkenes has been developed in the presence of bis(trifluoromethane)sulfonimide for the synthesis of trisubstituted alkenes and indane derivatives with high stereoselectivity.In general,benzylic alcohols react with 1,1-diaryl alkenes to afford trisubstituted alkenes,and the reaction with 1,2-disubstituted and trisubstituted alkenes affords indane derivatives through a [3 + 2] annulation reaction.     

Formal and standard ruthenium-catalyzed [2 + 2 + 2] cycloaddition reaction of 1,6-diynes to alkenes: a mechanistic density functional study

"Formal" and standard Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,6-diynes 1 to alkenes gave bicyclic 1,3-cyclohexadienes in relatively good yields. The neutral Ru(II) catalyst was formed in situ by mixing equimolecular amounts of [Cp*Ru(CH3CN)3]PF6 and Et4NCl. Two isomeric bicyclic 1,3-cyclohexadienes 3 and 8 were obtained depending on the cyclic or acyclic nature of the alkene partner. Mechanistic studies on the Ru catalytic cycle revealed a clue for this difference: (a) when acyclic alkenes were used, linear coupling of 1,6-diynes with alkenes was observed giving 1,3,5-trienes 6 as the only initial reaction products, which after a thermal disrotatory 6e-pi electrocyclization led to the final 1,3-cyclohexadienes 3 as probed by NMR studies. This cascade process behaved as a formal Ru-catalyzed [2 + 2 + 2] cycloaddition. (b) With cyclic alkenes, the standard Ru-catalyzed [2 + 2 + 2] cycloaddition occurred, giving the bicyclic 1,3-cyclohexadienes 8 as reaction products. A complete catalytic cycle for the formal and standard Ru-catalyzed [2 + 2 + 2] cycloaddition of acetylene and cyclic and acyclic alkenes with the Cp*RuCl fragment has been proposed and discussed based on DFT/B3LYP calculations. The most likely mechanism for these processes would involve the formation of ruthenacycloheptadiene intermediates XXIII or XXVII depending on the alkene nature. From these complexes, two alternatives could be envisioned: (a) a reductive elimination in the case of cyclic alkenes 7 and (b) a beta-elimination followed by reductive elimination to give 1,3,5-hexatrienes 6 in the case of acyclic alkenes. Final 6e-pi electrocyclization of 6 gave 1,3-cyclohexadienes 3.     

Copper‐Catalyzed Formal [2+2+1] Heteroannulation of Alkenes,Alkylnitriles, and Water: Method Development and Application to a Total Synthesis of (±)‐Sacidumlignan D

A copper‐catalyzed three‐component reaction of alkenes, alkylnitriles, and water affords γ‐butyrolactones in good yields. The domino process involves an unprecedented hydroxy‐cyanoalkylation of alkenes and subsequent lactonization with the creation of three chemical bonds and a quaternary carbon center. The synthetic potential of this novel [2+2+1] heteroannulation reaction was illustrated by a concise total synthesis of (±)‐sacidumlignan D.     

Copper‐Catalyzed Formal [2+2+1] Heteroannulation of Alkenes,Alkylnitriles, and Water: Method Development and Application to a Total Synthesis of (±)‐Sacidumlignan D

A copper‐catalyzed three‐component reaction of alkenes, alkylnitriles, and water affords γ‐butyrolactones in good yields. The domino process involves an unprecedented hydroxy‐cyanoalkylation of alkenes and subsequent lactonization with the creation of three chemical bonds and a quaternary carbon center. The synthetic potential of this novel [2+2+1] heteroannulation reaction was illustrated by a concise total synthesis of (±)‐sacidumlignan D.     

Recent advances in "formal" ruthenium-catalyzed [2+2+2] cycloaddition reactions of diynes to alkenes

"Formal" and standard RuII-catalyzed [2+2+2] cycloaddition of 1,6-diynes to alkenes gave bicyclic 1,3-cyclohexadienes in relatively good yields. When terminal 1,6-diynes 1 were used, two isomeric bicyclic 1,3-cyclohexadienes 4 or 6 were obtained, depending on the acyclic or cyclic nature of the alkene partner. When unsymmetrical substituted 1,6-diynes 7 were used, the reaction with acyclic alkenes took place regio- and stereoselectively to afford bicyclic 1,3-cyclohexadienes 8. A cascade process that behaves as a "formal" RuII-catalyzed [2+2+2] cycloaddition explained these results. Initially, a Ru-catalyzed linear coupling of 1,6-diynes 1 and 7 with acyclic alkenes occurs to give open 1,3,5-trienes of type 3, which after a thermal disrotatory 6e(-) pi-electrocyclization led to the final 1,3-cyclohexadienes 4 and 8. When disubstituted 1,6-diyne 10 was used with electron-deficient alkenes, new exo-methylene cyclohexadienes 12 arose from a competitive reaction pathway.     

Ruthenium-catalyzed carbonylative cycloaddition of alpha-keto lactones with alkenes or alkynes: the participation of an ester-carbonyl group in cycloaddition reactions as the two-atom assembling unit

The reaction of benzofuran-2,3-dione derivatives 1 with CO and alkenes (or alkynes) results in a carbonylative [2+2+1] cycloaddition in which the ester-carbonyl group is incorporated into a two-atom assembling unit to give spirolactone derivatives 2. This reaction provides the first example of an ester-carbonyl group participating in a carbonylative cycloaddition reaction.     

Palladium-catalyzed [2 + 2 + 2] cocyclotrimerization of benzynes with bicyclic alkenes: an efficient route to anellated 9,10-dihydrophenanthrene derivatives and polyaromatic compounds

An efficient method for the cocyclotrimerization of bicyclic alkenes and benzynes catalyzed by palladium phosphine complexes to give the corresponding norbornane anellated 9,10-dihydrophenanthrene derivatives is described. Bicyclic alkenes 1a-i undergo [2 + 2 + 2] cocyclotrimerization with benzynes generated from precursors 2a-d [2-(trimethylsilyl)phenyl triflate (2a), 4,5-dimethyl-2-(trimethylsilyl)phenyl triflate (2b), 6-(trimethylsilyl)-2,3-dihydro-1H-5-indenyl triflate (2c), 4-methyl-2-(trimethylsilyl)phenyl triflate (2d)] in the presence of PdCl(2)(PPh(3))(2) in acetonitrile at ambient temperature to yield anellated 9,10-dihydrophenanthrene products 3a-r in moderate to excellent yields. The [2 + 2 + 2] cocyclotrimerization products from oxa- and azabicyclic alkenes can be applied for the synthesis of polyaromatics, substituted benzo[b]triphenylenes (8a-f), via a simple Lewis acid mediated deoxyaromatization in good yields. In addition the [2 + 2 + 2] products undergo retro Diels-Alder reaction readily, providing a new method for the synthesis of substituted phenanthrenes and for generating isobenzofurans. A plausible mechanism is proposed to account for the catalytic [2 + 2 + 2] cycloaddition reaction.     

Alkene‐Directed N‐Attack Chemoselectivity in the Gold‐Catalyzed [2+2+1]‐Annulations of 1,6‐Enynes with N‐Hydroxyanilines

Kinetically unstable nitrones are generated from gold‐catalyzed reactions of 1,6‐enynes with N‐hydroxyanilines, and subsequently trapped by tethered alkenes to furnish [2+2+1]‐annulations. Our experimental data reveal that such nitrones arise from atypical N‐attack chemoselectivity that is triggered by tethered alkenes to facilitate the key protodeauration reaction.     

Computational Insights into Different Mechanisms for Ag-, Cu-, and Pd-Catalyzed Cyclopropanation of Alkenes and Sulfonyl Hydrazones

The [2+1] cycloaddition reaction of a metal carbene with an alkene can produce important cyclopropane products for synthetic intermediates, materials, and pharmaceutical applications. However, this reaction is often accompanied by side reactions, such as coupling and self-coupling, so that the yield of the cyclopropanation product of non-silver transition-metal carbenes and hindered alkenes is generally lower than 50 %. To solve this problem, the addition of a low concentration of diazo compound (decomposition of sulfonyl hydrazones) to alkenes catalyzed by either CuOAc or PdCl₂ was studied, but side reactions could still not be avoided. Interestingly, however, the yield of cyclopropanation products for such hindered alkenes were as high as 99 % with AgOTf as a catalyst. To explain this unexpected phenomenon, reaction pathways have been computed for four different catalysts by using DFT. By combining the results of these calculations with those obtained experimentally, it can be concluded that the efficiency of the silver catalyst is due to the barrierless concerted cycloaddition step and the kinetic inhibition of side reactions by a high concentration of alkene.     

Transition-metal-catalyzed formation of trans alkenes via coupling of aldehydes

[reaction: see text] Rh(2)(OAc)(4) catalyzed the formation of exclusively trans fluorinated alkenes from aldehydes and pentafluorobenzaldehyde tosylhydrazone salts, which were readily prepared from pentafluorobenzaldehyde using the Bamford-Stevens reaction. A series of pentafluorophenyl-containing alkenes were synthesized from aldehydes in moderate to good yields under mild reaction conditions in a one-pot reaction. It is the first report of coupling two different aldehydes to form exclusively trans alkenes.     

Regio- and stereochemistry of [2 + 2] photocycloadditions of imines to alkenes: a computational and experimental study

The [2 + 2] photocycloaddition of isoxazolines to alkenes has been studied by means of CASPT2/6-31G*//CASSCF/6-31G*. The reaction outcome is influenced by the relative ratio of imine deactivation and photocycloaddition. Analysis of the conical intersection points involved in the photoreaction shows that fast deactivation is prevented when an electron-withdrawing group is placed in any position that can affect the imine moiety. Computational data predict that the photoreaction will be regiospecific but without stereoselectivity. Furthermore, the favored regioisomer will be different for alkenes with electron-withdrawing or electron-releasing substituents. The results of a complementary experimental study correlate well with the computational data. Several conclusions included in the present work could prove useful for the generalization of the photocycloaddition of imines.     

Gold-catalyzed intermolecular reactions of propiolic acids with alkenes: [4 + 2] annulation and enyne cross metathesis

A gold-catalyzed intermolecular reaction of propiolic acids with alkenes led to a [4 + 2] annulation or enyne cross metathesis. The [4 + 2] annulation proceeds with net cis-addition with respect to alkenes and provides an expedient route to α,β-unsaturated δ-lactones, for which preliminary asymmetric reactions were also demonstrated. For 1,2-disubstituted alkenes, unprecedented enyne cross metathesis occurred to give 1,3-dienes in a completely stereospecific fashion. DFT calculations and experiments indicated that the cyclobutene derivatives are not viable intermediates and that the steric interactions during concerted σ-bond rearrangements are responsible for the observed unique stereospecificity.     

铱催化环加成反应的研究进展

过渡金属催化环加成反应是合成单环及多环化合物的重要方法,也是有机化学的研究热点之一.综述了近年来铱催化环加成反应的研究进展,主要包括了[2+2+1],[2+2+2],[4+2],1,3-偶极环加成反应等,及少量关于[3+2+2],[3+2],[5+1]环加成反应的报道,并讨论了部分铱催化环加成反应机理.     

Enantioselective Template‐Directed [2+2] Photocycloadditions of Isoquinolones: Scope,Mechanism and Synthetic Applications

A strategy for the enantioselective [2+2] photocycloaddition of isoquinolones with alkenes is presented, in which the formation of a supramolecular complex between a chiral template and the substrate ensures high enantioface differentiation by shielding one face of the substrate. Fifteen different electron‐deficient alkenes and ten different substituted isoquinolones undergo efficient photocycloaddition, yielding the cyclobutane products in excellent yields and with outstanding regio‐, diastereo‐ and enantioselectivities (up to 99 % ee). The mechanism of the reaction is investigated by means of triplet sensitization/quenching and radical clock experiments, the results of which are consistent with the involvement of a triplet excited state and a 1,4‐biradical intermediate. The variety of functionalized cyclobutanes obtained using this approach can be further increased by straightforward synthetic transformations of the photoadducts, allowing rapid access to libraries of compounds for various applications.     

Stereoselective [3+2] Carbocyclization of Indole‐Derived Imines and Electron‐Rich Alkenes: A Divergent Synthesis of Cyclopenta[b]indole or Tetrahydroquinoline Derivatives

An unprecedented stereoselective [3+2] carbocyclization reaction of indole‐2‐carboxaldehydes, anilines, and electron‐rich alkenes to obtain cyclopenta[b]indoles is disclosed. This pathway is different from the well‐established Povarov reaction: the formal [4+2] cycloaddition involving the same components, which affords tetrahydroquinolines. Moreover, by simply changing the Brønsted acid catalyst, this multicomponent coupling process could be divergently directed towards the conventional Povarov pathway to produce tetrahydroquinolines or to the new pathway (anti‐Povarov) to generate cyclopenta[b]indoles. Supported by computational studies, a stepwise Mannich/Friedel–Crafts cascade is proposed for the new anti‐Povarov reaction, whereas a concerted [4+2] cycloaddition mechanism is proposed for the Povarov reaction.     

Diastereoselective [3+2] Annulation of Aromatic/Vinylic Amides with Bicyclic Alkenes through Cobalt‐Catalyzed C−H Activation and Intramolecular Nucleophilic Addition

A highly diastereoselective method for the synthesis of dihydroepoxybenzofluorenone derivatives from aromatic/vinylic amides and bicyclic alkenes is described. This new transformation proceeds through cobalt‐catalyzed C?H activation and intramolecular nucleophilic addition to the amide functional group. Transition‐metal‐catalyzed C?H activation reactions of secondary amides with alkenes usually lead to [4+2] or [4+1] annulation; to the best of our knowledge, this is the first time that a [3+2] cycloaddition is described in this context. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. Mechanistic studies imply that the C?H bond cleavage may be the rate‐limiting step.     

Reactions of a metallacyclobutene complex with alkenes

The first productive reactions of a characterized metallacyclobutene complex with alkenes are reported. Thus, the metallacyclobutene complex (eta5-C5H5)(PPh3)Co[kappa2-(C,C)-C(SO2Ph) C(Si(CH3)3)CH(CO2CH2CH3)] (2) undergoes reaction with alkenes to give 1,4-diene complexes with a high degree of regio- and stereoselectivity. A mechanism is proposed in which the metallacyclobutene generates a cyclic vinylcarbene intermediate that undergoes [4 + 2]-cycloaddition reactions with activated alkenes. A model of the vinylcarbene intermediate has been examined using quantum mechanical methods.     

Synthesis of Cyclobutenes and Allenes by Cobalt‐Catalyzed Cross‐Dimerization of Simple Alkenes with 1,3‐Enynes

Cobalt‐catalyzed cross‐dimerization of simple alkenes with 1,3‐enynes is reported. A [2+2] cycloaddition reaction occurred, with alkenes bearing no allylic hydrogen, by reductive elimination of a η³‐butadienyl cobaltacycle. On the other hand, aliphatic alkenes underwent 1,4‐hydroallylation by means of exo‐cyclic β‐H elimination. These reactions can provide cyclobutenes and allenes that were previously difficult to access, from simple substrates in a highly chemo‐ and regioselective manner.