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.     

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.     

Gold-catalyzed stereoselective synthesis of azacyclic compounds through a redox/[2 + 2 + 1] cycloaddition cascade of nitroalkyne substrates

We report a new redox/cycloaddition cascade on readily available 1-alkynyl-2-nitrobenzenes that produces complex azacyclic compounds stereoselectively. The core structures of the resulting products are constructed through a formal [2 + 2 + 1] cycloaddition among α-carbonyl carbenoids, nitroso species, and external alkenes.     

Intramolecular [2 + 2] cycloaddition reactions of alkynyl ether derived ketenes. A convenient synthesis of donor-acceptor cyclobutanes

Mild thermolysis of tert-butyl alkynyl ethers furnishes aldoketenes, which undergo facile [2 + 2] cycloaddition reactions with pendant di- and trisubstituted alkenes. A wide variety of cis-fused cyclobutanones are produced in moderate to high diastereoselectivity and good to excellent yields by this method, and free hydroxyl groups are tolerated in the ene-ynol ether starting materials. Enol-ynol ethers also undergo efficient reaction to produce donor-acceptor cyclobutanes in high yields.     

Phosphine-catalyzed [4 + 2] annulation and vinylogous addition reactions between 1,4-dien-3-ones and 1,1-dicyanoalkenes

Phosphine-catalyzed [4 + 2] annulation and vinylogous Michael addition reactions between 1,4-dien-3-ones and 1,1-dicyanoalkenes are presented. Under the catalysis of PBu(3) (20 mol %), 1,4-dien-3-ones like styryl ketones with 2-aryl 1,1-dicyanoalkenes as doubly activated alkenes readily undergo a formal [4 + 2] cycloaddition reaction, affording polysubstituted cyclohexanones in satisfactory yield and good diastereoselectivity; with the doubly activated alkenes bearing an acidic methyl or methylene at the 2-position, a vinylogous Michael addition of 1,4-dien-3-ones occurs under the same reaction conditions, giving a non-cyclized multifunctional adduct in good yield. These two phosphine-catalyzed transformations represent atom economical carbon-carbon bond forming reactions capable of rapid construction of molecular complexity. Based on experimental results, formation of the products has been mechanistically rationalized, and a phosphonium activation is proposed.     

Photochemical Decarbonylation of Oxetanone and Azetidinone: Spectroscopy,Computational Models,and Synthetic Applications**

Photoexcitation of cyclic ketones leads to the expulsion of carbon monoxide and a mixture of products derived from diradical intermediates. Here we show that synthetic utility of this process is improved if strained heterocyclic ketones are used. Photochemistry of 3-oxetanone and N-Boc-3-azetidinone has not been previously described. Decarbonylation of these 4-membered rings proceeds through a step-wise Norrish type I cleavage of the C−C bond from the singlet excited state. Ylides derived from both compounds are high-energy species that are kinetically stable long enough to undergo [3+2] cycloaddition with a variety of alkenes and produce substituted tetrahydrofurans and pyrrolidines. The reaction has a sufficiently wide scope to produce scaffolds that were either previously inaccessible or difficult to synthesize, thereby providing experimental access to new chemical space.     

Photochemical Decarbonylation of Oxetanone and Azetidinone: Spectroscopy,Computational Models,and Synthetic Applications**

Photoexcitation of cyclic ketones leads to the expulsion of carbon monoxide and a mixture of products derived from diradical intermediates. Here we show that synthetic utility of this process is improved if strained heterocyclic ketones are used. Photochemistry of 3-oxetanone and N-Boc-3-azetidinone has not been previously described. Decarbonylation of these 4-membered rings proceeds through a step-wise Norrish type I cleavage of the C−C bond from the singlet excited state. Ylides derived from both compounds are high-energy species that are kinetically stable long enough to undergo [3+2] cycloaddition with a variety of alkenes and produce substituted tetrahydrofurans and pyrrolidines. The reaction has a sufficiently wide scope to produce scaffolds that were either previously inaccessible or difficult to synthesize, thereby providing experimental access to new chemical space.     

`Inverse‐Electron‐Demand' Diels‐Alder Reactions of (E)‐3‐Diazenylbut‐2‐enes in Water

The cycloadditions of (E)‐3‐diazenylbut‐2‐enes 1 with a variety of alkenes 2 – 6 were carried out in water as well as in organic solvents. The reactions were always faster in heterogeneous aqueous medium than in the organic solvents. These conjugated diazenyl‐alkenes behave mainly as heterodienes, and the Diels‐Alder adducts are the sole or at least main reaction products. Pyrroles derived from zwitterionic [3+2] cycloaddition reactions were observed in some cases. The cycloaddition of 1a with (+)‐2‐(ethenyloxy)‐3,7,7‐trimethylbicyclo[4.1.0]heptane ( 5 ) is the first example of an asymmetric `inverse electron‐demand' Diels‐Alder reaction carried out in pure water.     

Synthesis and unusual [2+2] cycloaddition reactions of haloacetylenes activated with the trifluoroacetyl group

Halogenated trifluoroacetylacetylenes have been synthesized for the first time. It was shown that they undergo formally forbidden by the orbital-symmetry rules [2+2] cycloaddition reactions with nonactivated alkenes in the absence of light and catalyst. A possible mechanism for this transformation is suggested.     

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.     

Hetero [6+3] cycloaddition of fulvenes with N-alkylidene glycine esters: a facile synthesis of the delavayine and incarvillateine framework

[reaction: see text] In contrast to the [3+2] or [4+3] cycloaddition of N-metalated azomethine ylides and various alkenes, N-benzylidene glycine ethyl ester reacts with fulvenes to give the hetero [6+3] cycloaddition adducts with high stereoselectivity, constituting an efficient and novel route to [2]pyrindines.     

Intramolecular and intermolecular diels-alder reactions of acylhydrazones derived from methacrolein and ethylacrolein

The intramolecular Diels-Alder reactions of hydrazones derived from methacrolein or ethylacrolein and terminally unsaturated N-acyl-N-methylhydrazines have been investigated. The hydrazones 7b and 7c derived from N-methyl-N-pent-4-enoylhydrazine 3b were found to undergo intramolecular [4 + 2] cycloaddition above 140 °C and the pyridopyridazines 12 were isolated. The corresponding hydrazones 8b and 8c from N-methyl N-pent-4-ynoylhydrazone 4a reacted similarly and gave as the final products the pyridines 13. The scope of the reaction is limited, as was shown by the failure of several other terminally unsaturated hydrazones of β-unsaturated aldehydes to undergo intramolecular cycloaddition. These hydrazones did, however, undergo intermolecular [4 + 2] cyctoaddition to N-phenylmaleimide. Other hydraiones 15 of methacrolein. including the benzoylhydrazone and the phenylhydrazone, also reacted with N-phenylmaleimide to give the pyridine 14b by way of an isolable dihydropyridine 16.     

Rhodium(I)-Catalyzed Bridged [5+2] Cycloaddition of cis-Allene-vinylcyclopropanes to Synthesize the Bicyclo[4.3.1]decane Skeleton

Previously reported was that cis-ene-vinylcyclopropanes (cis-ene-VCPs) underwent Rh-catalyzed [5+2] reaction to give 5,7-fused bicyclic products, where vinylcyclopropane (VCP) acts as five-carbon synthon. Unfortunately, this reaction had very limited scope. Replacing the 2π component of cis-ene-VCPs to allene moiety, the corresponding cis-allene-VCPs did not undergo the expected normal [5+2] cycloaddition to give 5,7-fused bicyclic products. Instead, the challenging bicyclo[4.3.1]decane skeleton was obtained via an unprecedented bridged [5+2] cycloaddition. DFT calculations were applied to understand why this bridged [5+2] reaction is favored over the anticipated but not realized normal [5+2] reaction.     

Ruthenium-catalyzed [2+2] cycloadditions of alkynyl sulfides and alkynyl sulfones

Ruthenium-catalyzed [2+2] cycloadditions of bicyclic alkenes with alkynyl sulfides and alkynyl sulfones were investigated. The sulfide and sulfone moieties were found to be compatible with the Ru-catalyzed cycloadditions, giving the corresponding cyclobutene cycloadducts in good yields. The sulfonyl-containing cycloadducts can be transformed into a variety of products that are difficult to obtain via direct cycloaddition.     

Alkenes in [2+2+2] Cycloadditions

Participation of alkenes and allenes in [2+2+2] cycloaddition reactions has attracted much attention recently. This version of the well‐established alkyne cyclotrimerization renders interesting products, such as cyclohexadienes and other polycycles, through cascade processes. Many mechanistic variations are observed when using certain metal complexes as catalysts. The frequent generation of stereogenic centers has prompted the development of efficient asymmetric versions. This Minireview summarizes the efforts reported to date on the use of double bonds as partners in [2+2+2] cyclotrimerizations.     

Ruthenium‐Catalyzed Oxidative Transformations of Terminal Alkynes to Ketenes By Using Tethered Sulfoxides: Access to β‐Lactams and Cyclobutanones

The oxidation of in situ generated Ru vinylidenes to ketenes is realized with tethered sulfoxides. The result is a Ru‐catalyzed oxidative transformation of terminal alkynes to highly valuable ketenes. Moreover, the ketenes generated here were shown to undergo characteristic ketene [2+2] cycloaddition reactions with tethered alkenes and external imines, yielding synthetically versatile bicyclic cyclobutanones and β‐lactams, respectively.     

Mechanism, regioselectivity, and the kinetics of phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes

With the aid of computations and experiments, the detailed mechanism of the phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes has been investigated. It was found that this reaction includes four consecutive processes: 1) In situ generation of a 1,3-dipole from allenoate and phosphine, 2) stepwise [3+2] cycloaddition, 3) a water-catalyzed [1,2]-hydrogen shift, and 4) elimination of the phosphine catalyst. In situ generation of the 1,3-dipole is key to all nucleophilic phosphine-catalyzed reactions. Through a kinetic study we have shown that the generation of the 1,3-dipole is the rate-determining step of the phosphine-catalyzed [3+2] cycloaddition reaction of allenoates and electron-deficient alkenes. DFT calculations and FMO analysis revealed that an electron-withdrawing group is required in the allene to ensure the generation of the 1,3-dipole kinetically and thermodynamically. Atoms-in-molecules (AIM) theory was used to analyze the stability of the 1,3-dipole. The regioselectivity of the [3+2] cycloaddition can be rationalized very well by FMO and AIM theories. Isotopic labeling experiments combined with DFT calculations showed that the commonly accepted intramolecular [1,2]-proton shift should be corrected to a water-catalyzed [1,2]-proton shift. Additional isotopic labeling experiments of the hetero-[3+2] cycloaddition of allenoates and electron-deficient imines further support this finding. This investigation has also been extended to the study of the phosphine-catalyzed [3+2] cycloaddition reaction of alkynoates as the three-carbon synthon, which showed that the generation of the 1,3-dipole in this reaction also occurs by a water-catalyzed process.     

Intramolecular pyridone/enyne photocycloaddition: partitioning of the [4 + 4] and [2 + 2] pathways

Intramolecular photocycloaddition (>290 nm) between a 1,3-enyne and a 2-pyridone is far more selective than the intermolecular version; a three-atom linkage both controls regiochemistry and separates the [2 + 2] and [4 + 4] pathways. All four head-to-head, head-to-tail, tail-to-head, and tail-to-tail tetherings have been investigated. Linkage via the ene of the enyne leads to [2 + 2] products regardless of alkene geometry, whereas linkage through the yne results in [4 + 4] cycloadducts. The bridged 1,2,5-cyclooctatriene products of [4 + 4] cycloaddition are unstable and undergo a subsequent [2 + 2] dimerization reaction.     

Phosphine-catalyzed cycloadditions of allenic ketones: new substrates for nucleophilic catalysis

A range of phosphine-catalyzed cycloaddition reactions of allenic ketones have been studied, extending the scope of these processes from the more widely used 2,3-butadienoates to allow access to a number of synthetically useful products. Reaction of allenyl methyl ketone 4 with exo-enones afforded spirocyclic compounds in good regioselectivity and promising enantioselectivity via a [2 + 3] cycloaddtion. Aromatic allenyl ketones undergo a phosphine-promoted dimerization to afford functionalized pyrans, leading to a formal [2 + 4] Diels-Alder product, but did not react in the [2 + 3] cycloaddition. The results from other reactions that had found utility with 2,3-butadienoates are also reported.     

Rhodium(I)‐Catalyzed Bridged [5+2] Cycloaddition of cis‐Allene‐vinylcyclopropanes to Synthesize the Bicyclo[4.3.1]decane Skeleton

Previously reported was that cis‐ene‐vinylcyclopropanes (cis‐ene‐VCPs) underwent Rh‐catalyzed [5+2] reaction to give 5,7‐fused bicyclic products, where vinylcyclopropane (VCP) acts as five‐carbon synthon. Unfortunately, this reaction had very limited scope. Replacing the 2π component of cis‐ene‐VCPs to allene moiety, the corresponding cis‐allene‐VCPs did not undergo the expected normal [5+2] cycloaddition to give 5,7‐fused bicyclic products. Instead, the challenging bicyclo[4.3.1]decane skeleton was obtained via an unprecedented bridged [5+2] cycloaddition. DFT calculations were applied to understand why this bridged [5+2] reaction is favored over the anticipated but not realized normal [5+2] reaction.