[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.     

Photoannelation Reactions of 3‐(Alk‐1‐ynyl)cyclohept‐2‐en‐1‐ones

Irradiation (350 nm) of the newly synthesized 3‐(alk‐1‐ynyl)cyclohept‐2‐en‐1‐ones 1 and 2 leads to the selective formation of tricyclic head‐to‐head dimers. In the presence of 2,3‐dimethylbuta‐1,3‐diene, the (monocyclic) enone 1 affords trans‐fused 7‐alkynyl‐bicyclo[5.2.0]nonan‐2‐ones as major photoproducts, whereas photocycloaddition of benzocyclohept‐5‐en‐7‐one 2 to the same diene gives preferentially the eight‐membered cyclic allene 16 via ‘end‐to‐end’ cyclization of the intermediate allyl‐propargyl biradical 22 . On contact with acid, cycloocta‐1,2,5‐triene 16 isomerizes to cycloocta‐1,3,5‐triene 18 .     

Photocycloaddition of Cyclohex‐2‐enones to Penta‐1,2,4‐triene

Dihydrothiinone 9a undergoes photocycloaddition regioselectively to all three C?C bonds of penta‐1,2,4‐triene ( 10 ), the relative stabilities of the biradical intermediates determining the product distribution. In contrast, cyclohexenone 9b and dihydropyranone 9c afford more complex mixtures of bicyclo[4.2.0]octanones, which also turn out to be less stable on chromatographic workup, reflecting the higher strain due to the shorter bond lengths (C? O and C? C vs. C? S) in the six‐membered rings, respectively.     

Mo(CO)6- and [Rh(CO)2Cl]2-catalyzed allenic cyclocarbonylation reactions of alkynones: efficient access to bicyclic dienediones

Allenyl alkynones are efficiently transformed into fused bicyclic dienediones via cyclocarbonylation reaction conditions. Mo(CO)6/DMSO reaction conditions result in the formation of a bicyclo[3.3.0]octenone ring system, and the [Rh(CO)2Cl]2-catalyzed reaction affords bicyclo[4.3.0]nonenone and bicyclo[5.3.0]decenone scaffolds.     

Photocycloaddition of Cyclohex‐2‐enones to 2‐Methylbut‐1‐en‐3‐yne

Irradiation (350 nm) of 2‐alkynylcyclohex‐2‐enones 1 in benzene in the presence of an excess of 2‐methylbut‐1‐en‐3‐yne ( 2 ) affords in each case a mixture of a cis‐fused 3,4,4a,5,6,8a‐hexahydronaphthalen‐1(2H)‐one 3 and a bicyclo[4.2.0]octan‐2‐one 4 (Scheme 2), the former being formed as main product via 1,6‐cyclization of the common biradical intermediate. The (parent) cyclohex‐2‐enone and other alkylcyclohex‐2‐enones 7 also give naphthalenones 8 , albeit in lower yields, the major products being bicyclo[4.2.0]octan‐2‐ones (Scheme 4). No product derived from such a 1,6‐cyclization is observed in the irradiation of 3‐alkynylcyclohex‐2‐enone 9 in the presence of 2 (Scheme 4). Irradiation of the 2‐cyano‐substituted cyclohexenone 12 under these conditions again affords only traces of naphthalenone 13 , the main product now being the substituted bicyclo[4.2.0]oct‐7‐ene 16 (Scheme 5), resulting from [2+2] cycloaddition of the acetylenic C−C bond of 2 to excited 12 .     

Dimethylformamide Catalyzed Synthesis of Novel Heterocycles—Their Characterization and Antimicrobial Evaluation

Indandione 1 was brominated to yield 2‐bromoIndandione 2 , which further reacted with substituted thiocarbamides, carbamides, 2‐aminothiophenols, 2‐aminophenol, and triazole to furnished 3‐substituted aniline‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐1(5),3‐octadiene 3 , 3‐substituted aniline‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐1(5),3‐octadiene 4 , 2‐Thia‐5‐aza‐9‐oxo‐3,4‐(3′‐substituted) benzo‐7,8‐benzo‐bicyclo[4.3.0]‐1(6) nonene 5 , 2‐oxa‐5‐aza‐9‐oxo‐(3, 4)‐(7,8)‐dibenzo‐bicyclo[4.3.0]‐1(6) nonene 6 , 3′‐substituted‐(1′,2′,4′)triazolo[5,6‐b][indeno(2,3‐e)]‐1,3,4‐thiadiazine 7 , respectively. The structures of compounds were elucidated on the basis of spectral techniques, further the representative compounds were screened for their antimicrobial activity.     

A Facile Approach to Optically Active Hydroquinoline‐2‐carboxylates by a One‐Pot Asymmetric Michael/Transamination/Cyclization Process

An efficient one‐pot synthesis of optically active hydroquinoline‐2‐carboxylates from 1,3‐cyclohexanediones, β,γ‐unsaturated α‐keto ester, and benzylamine in the presence of a chiral base catalyst and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) with good diastereoselectivity and high enantioselectivity is described. The reaction proceeds by a sequential asymmetric Michael/transamination/cyclization process.     

Reduction vs. Addition: The Reaction of an Aluminyl Anion with 1,3,5,7‐Cyclooctatetraene

The potassium aluminyl complex K[Al(NON^Ar)] (NON=NON^Ar=[O(SiMe₂NAr)₂]^2?, Ar=2,6‐iPr₂C₆H₃) reacts with 1,3,5,7‐cyclooctatetraene (COT) to give K[Al(NON^Ar)(COT)]. The COT‐ligand is present in the asymmetric unit as a planar μ₂‐η²:η⁸‐bridge between Al and K, with additional K???π‐aryl interactions to neighboring molecules that generate a helical chain. DFT calculations indicate significant aromatic character, consistent with reduction to [COT]^2?. Addition of 18‐crown‐6 causes a rearrangement of the C₈‐carbocycle to form the isomeric 9‐aluminabicyclo[4.2.1]nona‐2,4,7‐triene anion.     

Rhodium(I)-catalyzed intramolecular pauson-khand-type [2 + 2 + 1] cycloaddition of allenenes

[reaction: see text] The novel [RhCl(CO)(2)](2)-catalyzed [2 + 2 + 1] cycloaddition of allenenes leading to the bicyclo[4.3.0]non-1(9)-en-8-one as well as the bicyclo[5.3.0]dec-1(10)-en-9-one skeletons has been developed. This method also provides a new procedure for the construction of the bicyclo[4.3.0]non-1(9)-en-8-one skeleton having an alkyl appendage at the ring juncture, which was hardly attained in a satisfactory yield by the Pauson-Khand reaction of the corresponding enynes.     

Photocycloaddition Reactions of 5,5‐Dimethyl‐3‐(3‐methylbut‐3‐en‐1‐ynyl)cyclohex‐2‐en‐1‐one

The title cyclohexenone 1d undergoes photodimerization selectively at the exocyclic C?C bond to give a 1 : 1 mixture of 1,2‐dialkynyl‐1,2‐dimethylcyclobutanes 6 and 7 . On irradiation in the presence of 2,3‐dimethylbuta‐1,3‐diene, 1d affords bicyclo[8.4.0]tetradeca‐1,2,3,7‐tetraen‐11‐one 9 . This – formal – (6+4)‐cycloadduct undergoes quantitative isomerization to 3‐cycloheptadienyl‐2,5,5‐trimethylcyclohex‐2‐enone 11 on treatment with basic silica gel.     

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.     

Total Syntheses of (±)‐Fawcettimine, (±)‐Fawcettidine, (±)‐Lycoflexine,and (±)‐Lycoposerramine‐Q

The total syntheses of four fawcettimine‐related Lycopodium alkaloids, (±)‐fawcettimine, (±)‐fawcettidine, (±)‐lycoposerramine‐Q, and (±)‐lycoflexine, were completed in a highly stereoselective manner. The Pauson–Khand reaction of 4‐methylidene‐6‐siloxyoct‐1‐en‐7‐yne followed by regio‐ and stereoselective hydrogenation led to the short‐step preparation of the bicyclo[4.3.0]nonenone intermediate bearing a methyl group with the required stereochemistry. The subsequent chemical manipulation of the bicyclic compound afforded the 6‐5‐9‐membered tricyclic dioxo compound, which was then transformed into the four targeted alkaloids in an alternative and more efficient fashion.     

Asymmetric Synthesis of Oxa‐Bridged Oxazocines through a Catalytic RhII/ZnII Relay [4+3] Cycloaddition Reaction

Oxa‐bridged oxazocines bearing three chiral carbon centers were synthesized efficiently through a bimetallic catalytic asymmetric tandem reaction of β,γ‐unsaturated α‐ketoesters with diazoimides. The process contained a rhodium‐promoted in situ generation of isomünchnone from diazoimide decomposition, and a [4+3]‐cycloaddition of β,γ‐unsaturated α‐ketoester catalyzed by a chiral N,N′‐dioxide‐Zn^II complex. Ligand‐accelerated catalysis was found, and a possible transition‐state model was proposed to explain the origin of stereoselectivity.     

Bromenium‐Catalysed Tandem Ring Opening/Cyclisation of Vinylcyclopropanes and Vinylcyclobutanes: A Metal‐Free [3+2+1]/[4+2+1] Cascade for the Synthesis of Chiral Amidines and Computational Investigation

We present a detailed study of a [3+2+1] cascade cyclisation of vinylcyclopropanes (VCP) catalysed by a bromenium species (Br^δ+? X^δ?) generated in situ, which results in the synthesis of chiral bicyclic amidines in a tandem one‐pot operation. The formation of amidines involves the ring‐opening of VCPs with Br? X, followed by a Ritter‐type reaction with chloramine‐T and a tandem cyclisation. The reaction has been further extended to vinylcyclobutane systems and involves a [4+2+1] cascade cyclisation with the same reagents. The versatility of the methodology has been demonstrated by careful choice of VCPs and VCBs to yield bicyclo[4.3.0]‐, ‐[4.3.1]‐ and ‐[4.4.0]amidines in enantiomerically pure form. On the basis of the experimental observations and DFT calculations, a reasonable mechanism has been put forth to account for the formation of the products and the observed stereoselectivity. We propose the existence of a π‐stabilised homoallylic carbocation at the cyclopropane carbon as the reason for high stereoselectivity. DFT studies at B3LYP/6‐311+G** and M06‐2X/6‐31+G* levels of theory in gas‐phase calculations suggest the ring‐opening of VCP is initiated at the π‐complex stage (between the double bond and Br? X). This can be clearly perceived from the solution‐phase (acetonitrile) calculations using the polarisable continuum model (PCM) solvation model, from which the extent of the ring opening of VCP was found to be noticeably high. Studies also show that the formation of zero‐bridge bicyclic amidines is favoured over other bridged bicyclic amidines. The energetics of competing reaction pathways is compared to explain the product selectivity.     

Manganese(III) Acetate Catalyzed Oxidative Radical Additions of α‐Dicarbonyl Compounds to 1‐ and 2‐Phenylcyclohepta‐1,3,5‐triene

Manganese(III) acetate catalyzed oxidative radical‐addition reactions of α‐dicarbonyl compounds such as methyl acetoacetate ( 6 ), acetylacetone ( 7 ), and dimedone ( 8 ) to the mixture of 1‐ and 2‐phenylcyclohepta‐1,3,5‐triene ( 4 and 5 ) were investigated (Scheme 1). The 1‐phenylcyclohepta‐1,3,5‐triene ( 4 ) formed mainly [2+3] and [4+3] dihydrofuran addition products derived from cycloheptatriene and [2+3] dihydrofuran addition products derived from the norcaradiene structure. The 2‐phenylcyclohepta‐1,3,5‐triene ( 5 ) formed mainly [6+3] dihydrofuran addition products derived from cycloheptatriene and [4+3] dihydrofuran addition products derived from the norcaradiene structure. The structures of isolated products were established by their spectroscopic data (IR, ¹H‐ and ¹³C‐NMR, MS, and elemental analysis) and comparison with literature data. The formation mechanism of the products is discussed.     

RhI‐Catalyzed Bimolecular Cyclization between Two Different 1,5‐Bisallenes: A Combinatorial One‐Step Approach to Heterosteroids and Mechanistic Implications

In this paper, a bimolecular‐cyclization reaction between two different bis(allene)s with at least one heteroatom as the tether under the catalysis of trans‐[RhCl(CO)(PPh₃)₂] is described. This protocol provides an efficient entry to different heterocyclic 18,19‐norsteroid‐like scaffolds. The tricyclic product was formed highly selectively from the cyclization reaction of bis(2,3‐butadienyl)sulfide with dimethyl 2‐bis(2′,3′‐butadienyl)malonate, which sheds light on the mechanism involving the metalla‐[4.3.0]‐bicyclic intermediate formed by the cyclometallation of the terminal and the internal C=C bonds of each of the two allene moieties in 2‐bis(2′,3′‐butadienyl)malonate.     

Synthesis of 1‐azabicyclic systems by double cyclization

5‐Cyano‐1‐azabicyclo[3.3.0]octane ( 1 ) was prepared in one step from 1,7‐dichloro‐4‐heptanone ( 4 ) under mild conditions. The application of this method for the preparation of 5‐cyano‐4,6‐dimethyl‐1‐azabicy‐clo[3.3.0]octane ( 11 ) gave two diastereomers in equilibrium. The NMR measurements of 11 and its reduced compound 15 showed that the major isomer is the cis‐exo form, and the minor isomer is the trans form. Molecular orbital calculations indicated that the cis‐exo form is more stable than the trans form, in agreement with the experimental results. Furthermore, 6‐cyano‐1‐azabicyclo[4.3.0]nonane ( 17 ) and 1‐azabicy‐clo[4.4.0]decane ( 19 ), both including a six‐membered ring, were prepared from appropriate haloketones by using this double cyclization method.     

Polymerisation du cyclononatriene-1,2,6

1,2,6-Cyclononatriene gives low molecular weight polymers in good yield using cationic or Ziegler-Natta catalysts. The monomer unit has a bicyclo [4.3.0] nonene type structure resulting from the opening of the two unsaturated sites, i.e. the carbon-carbon double bond and the allenic group, according to a transannular mechanism.     

Construction of Hexahydrophenanthrenes By Rhodium(I)‐Catalyzed Cycloisomerization of Benzylallene‐Substituted Internal Alkynes through C−H Activation

The treatment of benzylallene‐substituted internal alkynes with [RhCl(CO)₂]₂ effects a novel cycloisomerization by C(sp²)?H bond activation to produce hexahydrophenanthrene derivatives. The reaction likely proceeds through consecutive formation of a rhodabicyclo[4.3.0] intermediate, σ‐bond metathesis between the C(sp²)?H bond on the benzene ring and the C(sp²)?Rh^III bond, and isomerization between three σ‐, π‐, and σ‐allylrhodium(III) species, which was proposed based on experiments with deuterated substrates.     

Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]‐Catalyzed Stereoselective Construction of Functionalized Bicyclo[5.3.0]decane Frameworks

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3‐siloxy‐1,3,9‐triene‐7‐yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)₅(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl‐substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven‐membered rings were present. The reaction of (Z)‐enol silyl ethers proceeded through Cope rearrangement of cis‐divinylcyclopropane intermediates, and that of (E)‐enol silyl ethers by 1,4‐addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.