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.     

Synthesis of [3,3′(4H,4′H)‐Bi‐2H‐1,3‐oxazine]‐4,4′‐diones and Their Hydrolysis

The [3,3′(4H,4′H)‐bi‐2H‐1,3‐oxazine]‐4,4′‐diones 3a – 3i were obtained by [2+4] cycloaddition reactions of furan‐2,3‐diones 1a – 1c with aromatic aldazines 2a – 2d (Scheme 1). So, new derivatives of bi‐2H‐1,3‐oxazines and their hydrolysis products, 3,5‐diaryl‐1H‐pyrazoles 4a – 4c (Scheme 3), which are potential biologically active compounds, were synthesized for the first time.     

[2+2] Cycloaddition of 1,3‐Dienes by Visible Light Photocatalysis

[2+2] Photocycloadditions of 1,3‐dienes represent a powerful yet synthetically underutilized class of reactions. We report that visible light absorbing transition metal complexes enable the [2+2] cycloaddition of a diverse range of 1,3‐dienes. The ability to use long‐wavelength visible light is attractive because these reaction conditions tolerate the presence of sensitive functional groups that might be readily decomposed by the high‐energy UVC radiation required for direct photoexcitation of 1,3‐dienes. The resulting vinylcyclobutane products are poised for a variety of further diversification reactions, and this method is consequently expected to be powerfully enabling in the synthesis of complex organic targets.     

Copper‐Catalyzed Aminothiolation of 1,3‐Dienes via a Dihydrothiazine Intermediate

Heteroatom‐containing organic molecules are of particular interest to medicinal chemists and materials scientists. A strategy to reach these architectures via direct difunctionalization of abundant 1,3‐dienes is especially attractive. Herein, we describe the development of a regio‐ and diastereoselective 1,4‐aminothiolation of 1,3‐dienes with a sulfur diimide reagent, a copper catalyst, and alkyl Grignard reagents. This unique protocol provides remote nitrogen and sulfur functionalities with high levels of stereocontrol. The reaction proceeds via a tandem hetero‐Diels–Alder cycloaddition of N,N′‐bis(benzenesulfonyl)sulfur diimide with 1,3‐diene followed by copper‐catalyzed Grignard substitution. Mechanistic studies support a copper catalyzed formation of an unprecedented [10‐S‐4] sulfurane that reductively eliminates to afford a 3,6‐dihydrothiazine, which is selectively converted to 1,4‐aminothiols.     

Regioselective Synthesis of 5‐(2‐Cyanoethyl)‐1,1′‐biphenyl‐2‐carboxylates by Formal [3+3] Cyclocondensations of 1,3‐Bis[(trimethylsilyl)oxy]buta‐ 1,3‐dienes

5‐(2‐Cyanoethyl)‐1,1′‐biphenyl‐2‐carboxylates were prepared by regioselective formal [3+3] cyclocondensations of 1,3‐bis[(trimethylsilyl)oxy]buta‐1,3‐dienes.     

Regioselective Synthesis of 4‐(Arylsulfanyl)‐2‐hydroxyhomophthalates by [4+2] Cycloaddition of 3‐(Arylsulfanyl)‐1‐(trimethylsilyloxy)buta‐1,3‐dienes with Dimethyl Penta‐2,3‐dienedioate

The [4+2] cycloaddition of 3‐(arylsulfanyl)‐1‐(trimethylsilyloxy)buta‐1,3‐dienes with dimethyl penta‐2,3‐dienedioate provides a convenient and regioselective approach to a variety of 4‐(arylsulfanyl)‐2‐hydroxyhomophthalates.     

Synthesis of β‐Lactam‐containing Pyrido[3′,2′:4,5]thieno[3,2‐e][1,4]diazepines

Novel tricyclic 1,4‐diazepine derivatives – pyrido[3′,2′:4,5]thieno[3,2‐e ][1,4]diazepin‐2‐ones – have been synthesized. Azetidin‐2‐one moiety has been incorporated into the 1,4‐diazepine scaffold by [2 + 2]cycloaddition of functionalized ketenes to imine C═N bond, and several tetracyclic azetodiazepines which can be considered as potential compounds of biological interest have been prepared. Stereoselectivity of the cycloaddition was proved by NMR and X‐ray analysis data.     

γ′‐Selective Functionalization of Cyclic Enones: Construction of a Chiral Quaternary Carbon Center by [4+2] Cycloaddition/Retro‐Mannich Reaction with 3‐Substituted Maleimides

The first example of organocatalyzed γ′‐selective functionalization of cyclic enones with 3‐substituted maleimides results in the stereoselective construction quaternary carbon center is presented. The reactions provided γ′‐functionalized cyclic enones and β‐functionalized cyclopentenones in good to excellent yields with excellent diastereo‐ and enantioselectivities. DFT calculations indicated that the reaction might proceed as a [4+2] cycloaddition/retro‐Mannich reaction which could explain the unexpected product with a chiral quaternary carbon center and the excellent stereoselectivity.     

Cycloadditions of Diarylgermylenes to a Diazabutadiene [1]

The reaction of tetrakis(2‐tert‐butyl‐4,5,6‐trimethylphenyl)digermene, which dissociates into the germylene molecules 2 in solution, with 1,4‐diisopropyl‐1,4‐diazabuta‐1,3‐diene ( 3 ) furnishes the [4+1] cycloaddition product of 2 to the nitrogen atoms of 3 . Under drastic conditions tetrakis(2,4,6‐triisopropylphenyl)digermene also forms the germylene molecules 6 which react with 3 in a similar fashion to afford the corresponding [4+1] cycloadduct.     

Multiple Cycloaddition Reactions of Ketones with a β‐Diketiminate Al Compound

A β‐diketiminate Al compound ( 1 ) with an exocyclic double bond reacts with two equivalents each of benzophenone and 2‐benzoylpyridine in a [4+2] cycloaddition to generate bicyclic and tricyclic compounds 2 and 3, respectively. Compound 2 consists of six‐ and eight‐membered aluminium rings, whereas 3 has two five‐ and one eight‐membered ring. Compounds 2 and 3 were characterized by a number of analytical tools including single‐crystal X‐ray diffraction. The quantum mechanical calculations suggest that the dissociation of the solvent molecule from 1 would lead to an active species 1A having two 1,4‐dipolar 4π electron moieties, in which the electrophilic site is the Al atom and the nucleophilic positions are polarized exocyclic and endocyclic C?C π bonds. The detailed mechanistic study shows that the dipolarophiles, benzophenone, and 2‐benzoylpyridine undergo double cycloaddition with two 1,4‐dipolar 4π electron moieties of 1A . Herein, the addition of one molecule of the dipolarophile promotes the addition of the second one.     

Synthesis,Interionic Structure,and Reactivity toward CO and p‐Methylstyrene of Palladacyclic Compounds Bearing α‐Diimine Ligands

Palladacyclic compounds [Pd(C₆H₄(C₆H₅C?O)C?N? R)(N? N)] [X] (R = Et, ⁱPr, 2,6‐ⁱPr₂C₆H₃; N? N = bpy = 2,2′‐bipyridine, or 1,4‐(o,o′‐dialkylaryl)‐1,4‐diazabuta‐1,3‐dienes; [X]^? = [BF₄]^? or [PF₆]^?) were synthesized from the dimers [{Pd(C₆H₄(C₆H₅C?O)C?N? R)(μ‐Cl)}₂] and N? N ligands. Their interionic structure in CD₂Cl₂ was determined by means of ¹⁹F,¹H‐HOESY experiments and compared with that in the solid state derived from X‐ray single‐crystal studies. [Pd(C₆H₄(C₆H₅C?O)C?N? R)(N? N)] [X] complexes were found to copolymerize CO and p‐methylstyrene affording syndiotactic or isotactic copolymers when bpy or 1,4‐(o,o′‐dimethylaryl)‐1,4‐diazabuta‐1,3‐dienes were used, respectively. The reactions with CO and p‐methylstyrene of the bpy derivatives were investigated. Two intermediates derived from a single and a double insertion of CO into the Pd? C bonds were isolated and completely characterized in solution.     

Ruthenium‐Catalyzed [2+2+2] Cycloaddition of 1,6‐Enynes and Unactivated Alkynes: Access to Ring‐Fused Cyclohexadienes

The [2+2+2] intermolecular carbocyclization reactions between 1,6‐enynes and alkynes catalyzed by [RuCl(cod)(Cp*)] (cod=1,5‐cyclooctadiene, Cp*=pentamethylcyclopentadienyl) are reported to provide bicyclohexa‐1,3‐dienes. The presented reaction conditions are compatible with internal and terminal alkynes and the chemo‐ and regioselectivity issues are controlled by the presence of substituents at the propargyl carbon center of the alkyne(s) partner(s).     

Mechanistic Intricacies of Gold‐Catalyzed Intermolecular Cycloadditions between Allenamides and Dienes

The mechanism of the gold‐catalyzed intermolecular cycloaddition between allenamides and 1,3‐dienes has been explored by means of a combined experimental and computational approach. The formation of the major [4+2] cycloaddition products can be explained by invoking different pathways, the preferred ones being determined by the nature of the diene (electron neutral vs. electron rich) and the type of the gold catalyst (AuCl vs. [IPrAu]⁺, IPr=1,3‐bis(2,6‐diisopropylphenyl)imidazole‐2‐ylidene). Therefore, in reactions catalyzed by AuCl, electron‐neutral dienes favor a concerted [4+3] cycloaddition followed by a ring contraction event, whereas electron‐rich dienes prefer a stepwise cationic pathway to give the same type of formal [4+2] products. On the other hand, the theoretical data suggest that by using a cationic gold catalyst, such as [IPrAuCl]/AgSbF₆, the mechanism involves a direct [4+2] cycloaddition between the diene and the gold‐activated allenamide. The theoretical data are also consistent with the observed regioselectivity as well as with the high selectivity towards the formation of the enamide products with a Z configuration. Finally, our data also explain the formation of the minor [2+2] products that are obtained in certain cases.     

A Novel,One‐Pot Four‐Component Route to 2′‐Thioxo‐2′,3′‐dihydrospiro[indole‐3,6′‐[1,3]thiazin]‐2‐one Derivatives

An efficient route to 2′,3′‐dihydro‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives is described. It involves the reaction of isatine, 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one, and different amines in the presence of CS₂ in dry MeOH at reflux (Scheme 1). The alkyl carbamodithioate, which results from the addition of the amine to CS₂, is added to the α,β‐unsaturated ketone, resulting from the reaction between 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one and isatine, to produce the 3′‐alkyl‐2′,3′‐dihydro‐4′‐phenyl‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives in excellent yields (Scheme 2). Their structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses.     

Palladium‐Catalyzed Formal [4+2] Cycloaddition of Benzoic and Acrylic Acids with 1,3‐Dienes via C—H Bond Activation: Efficient Access to 3,4‐Dihydroisocoumarin and 5,6‐Dihydrocoumalins

We report a palladium‐catalyzed formal intermolecular [4+2] cycloaddition of benzoic and acrylic acids with 1,3‐dienes including the stock chemicals 1,3‐butadiene and isoprene leading to synthetically useful 3,4‐dihydroisocoumarins and 5,6‐dihydrocoumalins. Stepwise C—H bond cleavage and annulation are likely involved in the reaction pathway. The synthetic potential of the methodology was demonstrated by two short derivatizations and total synthesis of natural product Clausamine B.     

One‐Pot Synthesis of Dispiro[oxindole‐3,3′‐pyrrolidines] by Three‐Component [3+2] Cycloadditions of in situ‐Generated Azomethine Ylides with 3‐Benzylidene‐2,3‐dihydro‐1H‐indol‐2‐ones

An efficient one‐pot, three‐component synthesis of novel dispiro[oxindole‐3,3′‐pyrrolidines] by 1,3‐dipolar cycloaddition of azomethine ylides, in situ generated by reaction of 1,2‐diones with sarcosine and subsequent decarboxylation, with a series of (E)‐3‐benzylidene‐2,3‐dihydro‐1H‐indol‐2‐ones is reported. Molecular complexity is generated in only one synthetic step. All reactions proceed with excellent regioselectivity and in good‐to‐excellent yields. The workup is easy, the reaction times are short, and no catalyst is required.     

A Functionalized Spiro[chlorin‐porphyrin]‐Type ‘Dimer’ Dizinc Complex from Rapid [4+2] Self‐cycloaddition of a Conjugated [β,β′‐Bis(methylene)porphyrinato]zinc

Thermal extrusion of SO₂ from β,β′‐sulfolenoporphyrins is an effective method for in situ generation of β,β′‐bis(methylene)porphyrin which remained unobserved in typical synthetic applications but underwent quickly efficient [4+2]‐cycloaddition reactions with dienophiles.We now report the thermal extrusion of SO₂ from the symmetrical (tetra‐β,β′‐sulfolenoporphyrinato)zinc 1?Zn in the absence of a dienophile (Scheme). In the event, the thermally in situ generated conjugated diene underwent a [4+2] self‐cycloaddition, to give the {spirobi[tri‐β,β′‐sulfolenoporphyrinato]}dizinc 4?2Zn . This chiral (racemic) spirobiporphyrinoid dizinc complex represents the combination of the closely positioned and interacting chromophores of a (porphyrinato)zinc and of a (β‐methylene‐β,β′‐dihydroporphyrinato)zinc. It carries six sulfoleno moieties that are still available for further SO₂ extrusion and cycloaddition reactions.     

Study of 1,3‐Dipolar Cycloaddition and Ring Contraction of New 1,4‐Phenylene‐bis[1,5]benzothiazepine Derivatives

Some 1,4‐phenylene‐bis[1,2,4]oxadiazolo‐[5,4‐d][1,5]benzothiazepine derivatives ( 4a , 4b , 4c ) were synthesized by 1,3‐dipolar cycloaddition reaction of benzohydroximinoyl chloride with 1,4‐phenylene‐bis(4‐aryl)‐2,3‐dihydro[1,5]benzothiazepine ( 2a , 2b , 2c ); meanwhile, compounds 2a , 2b , 2c also occurred ring contraction under acylating condition to obtain bis[2‐aryl‐2′‐(β‐1,4‐phenylenevinyl)‐3‐acetyl]‐2,3‐dihydro[1,5]benzothiazoles ( 3a , 3b , 3c ). The structures of some novel compounds were confirmed by IR, ¹H‐NMR, elemental, and X‐ray crystallographic analysis.     

Unexpected Spiroproducts from the Reaction of N‐Benzoylglycine with Ortho‐Formylbenzoic Acids −3,5′‐Dioxo‐2′‐Phenyl‐1,3‐Dihydrospiro[Indene‐2,4′‐[1,3]Oxazol]‐1‐yl Acetates: Establishments of Their Structure

This paper describes a method of preparation of new 3,5′‐dioxo‐2′‐phenyl‐1,3‐dihydrospiro[indene‐2,4′‐[1,3]oxazol]‐1‐yl acetate and its 5‐chloro‐ and bromoderivatives as products of interaction of N‐benzoylglycine (hippuric acid) with corresponding ortho‐formylbenzoic acids. The reaction carried out in acetic anhydride media in the presence of piperidine as catalyst. The novel spirocompounds were purified by column chromatography from multicomponent reaction mixtures. The composition of the spiro‐products was confirmed by C, H, N element analysis. The structure was established by IR, MS, ¹H‐ and ¹³C‐NMR analysis including COSY ¹H‐¹³C experiments.