Intramolecular Benzyne–Phenolate [4+2] Cycloadditions

An intramolecular benzyne–phenolate [4+2] cycloaddition is reported. Benzyne precursors, having vicinal halogen-sulfonate functionalities, linked with a phenol(ate) by various tether groups undergo efficient intramolecular [4+2] cycloaddition by treatment with either Ph₃MgLi or nBuLi for halogen–metal exchange to form various benzobarrelenes.     

Catalytic Asymmetric Intramolecular [4+2] Cycloaddition of In Situ Generated ortho‐Quinone Methides

Herein, we describe the first catalytic asymmetric intramolecular [4+2] cycloaddition of in situ generated ortho‐quinone methides. In the presence of a confined chiral imidodiphosphoric acid catalyst, various salicylaldehydes react with dienyl alcohols to give transient ortho ‐quinone methide intermediates, which undergo an intramolecular [4+2] cycloaddition to provide highly functionalized furanochromanes and pyranochromanes in excellent diastereoselectivity and enantioselectivity.     

Lewis Acid or Brønsted Acid Catalyzed Reactions of Vinylidene Cyclopropanes with Activated Carbon–Nitrogen,Nitrogen–Nitrogen,and Iodine–Nitrogen Double‐Bond‐Containing Compounds

Lewis acid or Brønsted acid catalyzed reactions of vinylidene cyclopropanes (VDCPs), 1 , with activated carbon–nitrogen, nitrogen–nitrogen, and iodine–nitrogen double‐bond‐containing compounds have been thoroughly investigated. We found that pyrrolidine and 1,2,3,4‐tetrahydroquinoline derivatives can be formed in good yields in the reactions of VDCPs 1 with ethyl (arylimino)acetates 2 by a [3+2] cycloaddition or intramolecular Friedel–Crafts reaction pathway. Based on these results, we found that activated carbon–nitrogen and nitrogen–nitrogen double‐bond‐containing compounds, such as N‐toluene‐4‐sulfonyl (N‐Ts) imines 5 and diisopropylazodicarboxylate ( 7 ), can also react with VDCPs 1 to give [3+2] cycloaddition products in moderate to good yields in the presence of a Lewis acid. When N‐tert‐butoxycarbonyl aldimine 9 was used as the substrate, six‐membered cycloaddition products 10 and 11 were formed in moderate yields in the presence of a Brønsted acid, trifluoromethanesulfonic acid (TfOH). The reactions of VDCPs 1 with N‐Ts‐iminophenyliodinane ( 12 ) were also carried out in the presence of (CuOTf)₂ ? C₆H₆ and it was found that nitrogen‐containing indene derivatives 13 were obtained, rather than the aziridination products. Plausible mechanisms for all of these transformations are discussed, based on the obtained results.     

[6+2]Cycloadditions catalyzed by titanium complexes

The Ziegler catalyst TiCl₄-Et₂AlCl and the arenetitanium(II) complex (η6-C₆H₆)Ti(II)(AlCl₄)₂ induce [6 + 2]cycloaddition reactions of cycloheptatriene with dienes and acetylenes. Addition to 1,3-butadiene affords 7 - endo - vinyl - bicyclo[4.2.1]nona - 2,4 - diene (main product) and bicyclo[4.4.1]- undeca - 2,4,8 - triene, a product of [6+4]cycloaddition. Isoprene reacts similarly, yielding mainly 7- endo - isopropenyl - bicyclo[4.2.1]nona - 2,4 - diene. 2,3 - Dimethyl - 1,3 - butadiene gives 8,9dimethylbicyclo [4.4.1]undeca - 2,4,8 - triene, a product of [6 + 4]cycloaddition, while [6 + 2]cross-adducts are minor products. The reaction of cycloheptatriene with norbornadiene gives mainly hexacyclo[6.5.1.0^2,7.0^3,12.^6,10.0^9,13]tetradec - 4 - ene via [6+2]cycloaddition followed by intramolecular Diels-Alder reaction. As a by-product, pentacyclo[7.5.0.0^2,7.0^3,5.0⁴⁸]tetradeca - 10,12 - diene is formed by a [2+2+2]mechanism. Addition of cycloheptatriene to diphenylacetylene and bis - (tri- methylsilyl)acetylene furnishes sustituted bicyclo[4.2.1]nona - 2,4,7 - trienes. Alkenes, E,E-2,4 - hexadiene and 1,3 - cyclooctadiene are unreactive. The [6+2]cycloaddition is made possible by coordination of cycloheptatriene to titanium, which changes the symmetry of the frontier orbitals in the triene. The reactivity of the trienophile is also enhanced by coordination to the catalyst.     

Studies in the furan series. 23. Preparation of some new 5-substituted furfurylallylarylamines. Influence of substituents on the intramolecular Diels-Alder (IMDA) reaction

Several new N-allyl-N-(5-substituted)-2-furfuryl-p)-toluidines IIIa-e with Cl, Br, I, NO₂ or CH₃O groups in position 5 of the furan nucleus were prepared by allylation of the corresponding secondary furfurylaryl-amines. Both, electron withdrawing and releasing substituents enhanced the yield of intramolecular [4+2] cycloaddition.     

A Catalytic Diastereoselective Formal [5+2] Cycloaddition Approach to Azepino[1,2‐a]indoles: Putative Donor–Acceptor Cyclobutanes as Reactive Intermediates

A catalytic formal [5+2] cycloaddition approach to the diastereoselective synthesis of azepino[1,2‐a]indoles is reported. The reaction presumably proceeds through a Lewis acid catalyzed formal [2+2] cycloaddition of an alkene with an N‐indolyl alkylidene β‐amide ester to form a donor–acceptor cyclobutane intermediate, which subsequently undergoes an intramolecular ring‐opening cyclization. Azepine products are formed in up to 92 % yield with high degrees of diastereoselectivity (up to 34:1 d.r.).     

Isobutane chemical ionization mass spectra of unsaturated alcohols

Analysis of the isobutane chemical ionization mass spectra of hexenols, cyclohexenols and various syn/anti pairs of bicyclic and tricyclic homoallylic alcohols shows that: (i) the spectra of the allylic alcohols are dominated by [M + H – H₂O]⁺ and [M + C₄H₉–H₂O]⁺ ions and contain traces of [M + H]⁺ ions; (ii) [M + H]⁺ ions are prominent in the spectra of acyclic and certain cyclic homoallylic alcohols; and (iii) [M + H]⁺ ions dominate the spectra of other acyclic unsaturated alcohols. The [M + H]⁺ ions may result from either: (a) protonation of the hydroxyl group, followed by a very rapid intramolecular proton transfer from the protonated hydroxyl group to the carbon–carbon double bond or internal solvation of the protonated hydroxyl group by the carbon–carbon double bond; and/or (b) direct protonation of the carbon–carbon double bond with significant internal solvation of the resulting carbocation by the hydroxyl group, which may lead to carbon–oxygen bond formation to give a protonated cyclic ether. The consequences of placing various geometric constraints on the possible intramolecular interactions between the hydroxyl group and the carbon–carbon double bond in unsaturated alcohols are explored.     

Thermische und photochemisch induzierte intramolekulare, 1,3-dipolare Cycloadditionen von 4-Phenyl-3-(2-allylphenyl)-sydnon. Vorläufige Mitteilung. 53. Mitteilung über Photoreaktionen

Thermal and photochemically induced intramolecular 1,3-dipolar cycloaddition reactions of 4-phenyl-3-(2-allylphenyl)-sydnone The title compound 9 was synthesised in the usual way, starting from 2-allylaniline and ethyl 2-bromo-2-phenylacetate, via the nitrosaminacid 8 (Scheme 2). 9 reacts at room temperature with its potential azomethinimine-function in an intramolecular [3+2]-cycloaddition to give the tricyclic compound 11 (Scheme 2). On irradiation, 9 yields the dihydro-3H-pyrazolo[2,3-a]indole 10 which probably arises by intramolecular [3+2]-cycloaddition of the corresponding intermediate nitrilimine.     

GeCl<Subscript>2</Subscript> cycloaddition reactions to unsaturated organic compounds taking ethylene,buta-1,3-diene,and hexa-1,3,5-triene as examples: a quantum chemical study

The cycloaddition reactions of dichlorogermylene GeCl₂ to ethylene, buta-1,3-diene, and hexa-1,3,5-triene were studied within the framework of the density functional theory (PBE and B3LYP density functionals) and by the ab initio CBS-QB3 method. The energy characteristics of the reaction of GeCl₂ with ethylene were refined and non-empirical quantum chemical calculations of reaction pathways in the GeCl₂ + buta-1,3-diene and GeCl₂ + hexa-1,3,5-triene systems were carried out for the first time. It was shown that the [2+1] cycloaddition reactions are kinetically hindered and thermodynamically unfavorable, while the [4+1] and [6+1] cycloaddition reactions are characterized by low barriers and result in thermodynamically favorable products. For the [4+1] cycloaddition to buta-1,3-diene and [6+1] cycloaddition to hexa-1,3,5-triene, the most energetically favorable reaction pathways involve a suprafacial and antarafacial approach of reactants, respectively.     

Intramolecular [4 + 2] cycloaddition reactions of pyridazino-[4,5-d]pyridazines with acetylenic side-chain dienophiles: Synthesis of f-annelated phthalazines

Starting from the thione 1 , a series of 1-(alkynyl-X)-4-phenylpyridazino[4,5-d]pyridazines 4–8 (X = 0, NH, S) was prepared. Thermally induced intramolecular [4+2] cycloaddition reactions of the ethers 4, 5 and the thioether 8 afforded f-annelated phthalazine derivatives.     

One Stone for Three Birds‐Rhodium‐Catalyzed Highly Diastereoselective Intramolecular [4+2] Cycloaddition of Optically Active Allene‐1,3‐dienes

RhCl(PPh₃)₃‐catalyzed [4+2] intramolecular cycloaddition of optically active axially chiral allene‐dienes afforded cis‐fused [3.4.0]‐bicyclic products with three chiral centers in good yields with an excellent chemo‐ and diastereoselectivity. A pair of enantiomers of such products was generated highly selectively from both enantiomers of starting allene‐dienes, indicating that the axial chirality dictated the absolute configurations of the three in situ generated chiral centers with a very high efficiency of chirality transfer.     

Crystal structure and photoreactivity of a halogen‐bonded cocrystal based upon 1,2‐diiodoperchlorobenzene and 1,2‐bis(pyridin‐4‐yl)ethylene

The formation of a photoreactive cocrystal based upon 1,2‐diiodoperchlorobenzene ( 1,2‐C₆I₂Cl₄ ) and trans‐1,2‐bis(pyridin‐4‐yl)ethylene ( BPE ) has been achieved. The resulting cocrystal, 2( 1,2‐C₆I₂Cl₄ )·( BPE ) or C₆Cl₄I₂·0.5C₁₂H₁₀N₂, comprises planar sheets of the components held together by the combination of I…N halogen bonds and halogen–halogen contacts. Notably, the 1,2‐C₆I₂Cl₄ molecules π‐stack in a homogeneous and face‐to‐face orientation that results in an infinite column of the halogen‐bond donor. As a consequence of this stacking arrangement and I…N halogen bonds, molecules of BPE also stack in this type of pattern. In particular, neighbouring ethylene groups in BPE are found to be parallel and within the accepted distance for a photoreaction. Upon exposure to ultraviolet light, the cocrystal undergoes a solid‐state [2 + 2] cycloaddition reaction that produces rctt‐tetrakis(pyridin‐4‐yl)cyclobutane ( TPCB ) with an overall yield of 89%. A solvent‐free approach utilizing dry vortex grinding of the components also resulted in a photoreactive material with a similar yield.     

A Novel N,P,C Cage Complex Formed by Rearrangement of a Tricyclic Phosphirane Complex: On the Importance of Non‐covalent Interactions

The reaction of Li/Cl P‐CPh₃ phosphinidenoid tungsten(0) complex 2 with dimethylcyanamide afforded tricyclic phosphirane complex 4 , an unprecedented rearrangement of which led to the novel N,P,C cage complex 6 . On the basis of DFT calculations, formation and intramolecular [3+2] cycloaddition of the transient nitrilium phosphane ylide complex 3 to a phenyl ring of the triphenylmethyl substituent to give 4 is proposed. Furthermore, theoretical evidence for terminal N‐amidinophosphinidene complex 7 , formed by [2+1] cycloelimination from 4 , is provided, and the role of the electronic structure and non‐covalent interactions of intermediate 7 discussed.     

The Cobalt Way to Angucyclinones: Asymmetric Total Synthesis of the Antibiotics (+)‐Rubiginone B2, (−)‐Tetrangomycin,and (−)‐8‐O‐Methyltetrangomycin

A cobalt(I)‐mediated convergent and asymmetric total synthesis of angucyclinones with an aromatic B ring has been developed. In the course of our research, we synthesized three naturally occurring anguclinone derivatives, namely, (+)‐rubiginone B₂ ( 1 ), (?)‐8‐O‐methyltetrangomycin ( 2 ), and (?)‐tetrangomycin ( 3 ). By combining 3‐hydroxybenzoic acid, 3‐methoxybenzoic acid, citronellal, and geraniol as starting materials in a convergent way, we were able to synthesize chiral triyne chains, which were cyclized with [CpCo(C₂H₄)₂] (Cp=cyclopentadienyl) by means of an intramolecular [2+2+2] cycloaddition to their corresponding tetrahydrobenzo[a]anthracenes. Successive oxidation and deprotection steps led to the above‐mentioned natural products 1 – 3 .     

Stereoselective Rhodium‐Catalysed [2+2+2] Cycloaddition of Linear Allene–Ene/Yne–Allene Substrates: Reactivity and Theoretical Mechanistic Studies

Allene–ene–allene ( 2 and 5 ) and allene–yne–allene ( 3 and 7 ) N‐tosyl and O‐linked substrates were satisfactorily synthesised. The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh₃)₃] was evaluated. Substrates 2 and 5 , which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. The reaction of substrates 3 and 7 , which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. A Diels–Alder reaction on N‐tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction.     

Phanes with Three- and Four-Membered Rings as Building Elements

The systematic integration of the small 2π- and 4π-electron systems cyclopropenylium ion, cyclopropenone, oxo-cyclobutenylium ion, and cyclobutadiene into phane chemistry was initiated only a few years ago. [n₂]Cyclopropenylophanes, [n₂]cyclopropenonophanes, metal-capped [n₄]cyclobutadienosuperphanes, and other new families of double-decker phane species became available from cycloalkydiynes through special methods of double [2+1]cycloaddition with carbenes and metal complex induced dimerization by double [2+2]cycloaddition. Phane-specific structural features were elucidated by X-ray structural analyses. Cyclic voltammetry and PE spectroscopy as well as MO calculations reealed considerable interactions between closely spaced π-electron systems. Decapping cyclobutadienosuperphanes formally extended the synthetic principle to threefold [2+2]cycloadditions resulting in [n₄]-bridged tricyclo-[4.2.0.0^{3, 5}]octa-3,7-dienes, which represent a new type of cage compounds. Moreover, completion to fourfold [2+2]addition was achieved with the photoinduced transformation of [3₄]bridged tricyclo[4.2.0.0^{3, 5}]octa-3,7-diene into propella[3₄]cubane.     

Multiple electronic state mechanism for carboryne reaction with benzene: A DFT study

The multiple electronic state mechanisms of the reaction of carboryne with benzene were investigated by M11 calculations. Mechanisms leading to [4 + 2] cycloaddition product P_{4 + 2} , [2 + 2] cycloaddition product P _{2 + 2} , C? C insert product P _C‐Cins and C? H insert product P _C‐Hins were considered. The barrier/stability to structural characteristics correlations revealed that, 1) [2 + 2] addition is a two‐step mechanism which exhibits three electronic state reactivity, and both the addition steps are controlled by the barriers on open‐shell singlet (OSS) potential energy surface (PES); 2) [4 + 2] product P _{4 + 2} is a kinetic product on the experimental condition, and other products should be obtained under more harsher condition. The theoretical results well explain the experimental facts.     

Rhodium-Catalyzed [2+1+2+1] Cycloaddition of Benzoic Acids with Diynes through Decarboxylation and C≡C Triple Bond Cleavage

It has been established that an electron-deficient cyclopentadienyl rhodium(III) (Cp^ERh^III) complex catalyzes the oxidative and decarboxylative [2+1+2+1] cycloaddition of benzoic acids with diynes through C≡C triple bond cleavage, leading to fused naphthalenes. This cyclotrimerization is initiated by directed ortho C−H bond cleavage of a benzoic acid, and the subsequent regioselective alkyne insertion and decarboxylation produce a five-membered rhodacycle. The electron-deficient nature of the Cp^ERh^III complex promotes reductive elimination giving a cyclobutadiene–rhodium(I) complex rather than the second intermolecular alkyne insertion. The oxidative addition of the thus generated cyclobutadiene to rhodium(I) (formal C≡C triple bond cleavage) followed by the second intramolecular alkyne insertion and reductive elimination give the corresponding [2+1+2+1] cycloaddition product. The synthetic utility of the present [2+1+2+1] cycloaddition was demonstrated in the facile synthesis of a donor–acceptor [5]helicene and a hemi-hexabenzocoronene by a combination with the chemoselective Scholl reaction.     

Rhodium‐Catalyzed Enantioselective [4+2] Cycloadditions of Vinylcarbenes with Dienes

The reaction of 2‐siloxycyclo‐1,3‐dienes with E‐vinyldiazoacetates in the presence of the bulky chiral dirhodium tetracarboxylate catalyst, Rh₂(R‐p‐PhTPCP)₄ results in an enantioselective [4+2] cycloaddition, in which three new stereogenic centers are formed. The [4+2] cycloadducts are generated as single diastereomers with high enantiocontrol (95–98 % ee). When the diene contains an additional stereogenic center, effective kinetic resolution can be achieved.     

Rhodium-Catalyzed Enantioselective [4+2] Cycloadditions of Vinylcarbenes with Dienes

The reaction of 2-siloxycyclo-1,3-dienes with E-vinyldiazoacetates in the presence of the bulky chiral dirhodium tetracarboxylate catalyst, Rh₂(R-p-PhTPCP)₄ results in an enantioselective [4+2] cycloaddition, in which three new stereogenic centers are formed. The [4+2] cycloadducts are generated as single diastereomers with high enantiocontrol (95–98 % ee). When the diene contains an additional stereogenic center, effective kinetic resolution can be achieved.