[2+4] vs [4+2] Cycloaddition reactions of o-thioquinones with 1,3-dienes

Under kinetic control, the reaction of o-thioquinones with acyclic 1,3-dienes afforded, as main products, the spiro cycloadducts deriving from the participation of the thiones as dienophiles. Under thermodynamic control, or with cyclic dienes, the thioquinones behave as hetero dienes to give the benzoxathiin derivatives with complete regioselectivity.     

Substituent Effects on Site Selectivity (C=C vs C=N) in Heterocumulene-Heterodiene [4 + 2] Cycloadditions: Density Functional and Semiempirical AM1 Molecular Orbital Calculations

The effect of substituents on the site selectivity (C=C vs C=N) in the [4 + 2] cycloaddition between heterocumulenes (ketene imines) 2a-g with heterodienes (acroleines 9a-n and 4-acylfuran-2,3-diones 1a-d) is treated by semiempirical AM1 molecular orbital and density functional calculations using Becke's three-parameter hybrid method (B3LYP/6-31G). For some reactions calculations were also done at the B3LYP/6-31+G level of theory. For reaction of the oxa 1,3-dienes with ketene imines unsubstituted at the terminal carbon invariably addition across the C=C heterocumulene double bond has a lower activation energy than addition across the C=N double bond. Substitution of methyl or especially phenyl groups at the ketene imine C-terminus leads to a reversal of the respective activation energies. Incorporation of the oxa 1,3-diene system into the heterocyclic dione 1 substantially enhances the reactivity ( approximately 10 kcal mol(-1) lower activation energies) as compared to similarly substituted acroleins. At the DFT level of theory all reactions are found to proceed via a concerted asynchronous mechanism.     

Transition metal-catalyzed [4 + 2 + 2] cycloadditions of bicyclo[2.2.1]hepta-2,5-dienes (norbornadienes) and bicyclo[2.2.2]octa-2,5-dienes

The transition-metal-catalyzed [4 + 2 + 2] cycloadditions of norbornadienes, bicyclo[2.2.2]octa-2,5-diene, and benzobarrelene with 1,3-butadienes proceed in excellent yields using cobalt-based catalytic systems. Two key distinctions between these [4 + 2 + 2] cycloadditions and the corresponding transition-metal-catalyzed [2 + 2 +2] reactions of norbornadiene are the requirement of a bimetal catalytic system with a bisphosphine ligand for the former and exclusive regioselectivity in the [4 + 2 + 2] reaction of 2-substituted norbornadienes to produce 1-substituted adducts. These distinctions may indicate two distinct mechanisms for the [4 + 2 + 2] and [2 + 2 + 2] reactions.     

[4 + 2] Cycloaddition reactions of hexachlorotropone

The cycloaddition of hexachlorotropone to selected olefins, including 1,3-dienes, has been examined. Unlike tropone, which undergoes [6 + 4] cycloadditions with 1,3-dienes, only [4 + 2] processes were observed with hexachlorotropone. Its apparent preference for exo-addition (contrast tetrachlorocyclopentadienone) probably results from thermodynamic control of the endo : exo product ratios.     

Formal intermolecular 4 + 4 approach to cyclooctanoids: 4 + 3 capture of the Nazarov oxyallyl intermediate with simple 1,3-dienes

[reaction: see text] Simple 1,4-dien-3-ones and 1,3-dienes react in the presence of BF(3).OEt(2) via a domino Nazarov electrocyclization/intermolecular [4 + 3]-cycloaddition sequence to furnish keto-bridged cyclooctenes in good yield. Most cases showed high diastereofacial selectivity and/or endo/exo selectivity, and surprising levels of regioselectivity were observed when isoprene was used as the diene partner.     

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 twist of the [8+2] cycloadditions of dienylisobenzofurans and dimethyl acetylenedicarboxylate: stepwise [8+2] versus [4+2]/[1,5]-vinyl shift mechanisms revealed through a theoretical and experimental study

Recently, it was reported that both dienylfurans and dienylisobenzofurans could react with dimethyl acetylenedicarboxylate (DMAD) to give [8+2] cycloadducts. Understanding these [8+2] reactions will aid the design of additional [8+2] reactions, which have the potential for the synthesis of 10-membered and larger carbocycles. The present Article is aimed to understand the detailed mechanisms of the originally reported [8+2] cycloaddition reaction between dienylisobenzofurans and alkynes at the molecular level through the joint forces of computation and experiment. Density functional theory calculations at the (U)B3LYP/6-31+G(d) level suggest that the concerted [8+2] pathway between dienylisobenzofurans and alkynes is not favored. A stepwise reaction pathway involving formation of a zwitterionic intermediate for the [8+2] reactions between dienylisobenzofurans that contain electron-donating methoxy groups present in their diene moieties and DMAD has been predicted computationally. This pathway is in competition with a Diels-Alder [4+2] reaction between the furan moieties of dienylisobenzofurans and DMAD. When there is no electron-donating group present in the diene moieties of dienylisobenzofurans, the [8+2] reaction occurs through an alternative mechanism involving a [4+2] reaction between the furan moiety of the tetraene and DMAD, followed by a [1,5]-vinyl shift. This computationally predicted novel mechanism was supported experimentally.     

Theoretical Study of Mechanism and Regioselectivity of 1,3-dipolar Cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] Nitrilimine with Dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate

The mechanism and regioselectivity of 1,3-dipolar cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] nitrilimine with dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate were investigated using activation energy calculations and density functional theory-based re-activity indexes. The reaction proceeds by an asynchronous concerted mechanism. The calculations are performed at the B3LYP/6-31G(d) level of theory and the obtained results are in agreement with experimental outcome.     

DFT study on the Diels-Alder cycloaddition between alkenyl-M(0) (M = Cr, W) carbene complexes and neutral 1,3-dienes

The thermal Diels-Alder reaction between alkenylmetal(0) Fischer carbenes and 1,3-dienes (isoprene and cyclopentadiene) has been studied computationally within the density functional theory framework. The selectivity of the [4 + 2] cycloadditions between alkenyl-group 6 (Fischer) carbene complexes and isoprene is similar to the selectivity computed for the reactions involving Lewis acid complexed acrylates. The experimentally observed complete endo selectivity in the [4 + 2] cycloadditions of alkenyl-group 6 (Fischer) carbene complexes with cyclopentadiene, which takes place under kinetic control, may be due in part to the presence of stabilizing secondary orbital interactions. These interactions are stronger than the analogues in the metal-free processes. The [4 + 2] cycloadditions between alkenyl-group 6 (Fischer) carbene complexes and neutral dienes occur concertedly via transition structures which are more asynchronous and less aromatic than their non-organometallic analogues, a behavior which is extensible to the reactions between Lewis acid complexed acrylates.     

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.     

[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.     

[2 + 2] Cycloaddition Reactions of Butadienyl Ketene with 1,4‐Diazabuta‐1,3‐dienes: Synthesis of Functionalized Butadienyl‐4‐iminomethyl‐azetidin‐2‐ones and Butenylidene‐butadienyl‐[2,2′‐biazetidine]‐4,4′‐diones

The reactions of butadienylketene with variety of 1,4‐diazabuta‐1,3‐dienes are studied. The reactions resulted in the formation of previously unknown functionalized cis butadienyl‐4‐iminomethyl‐azetidin‐2‐ones and butenylidene‐butadienyl‐[2,2′‐biazetidine]‐4,4′‐ diones. Butadienyl ketene reacts in [2+2] cycloaddition fashion with both iminic portion of 1,4‐ diazabuta‐1,3‐dienes and competitive [4+2] cycloaddition reaction of 1,4‐diazabuta‐1,3‐dienes as 4π component with butadienyl ketene as 2π component are not observed.     

Understanding the nature of the molecular mechanisms associated with the competitive Lewis acid catalyzed [4+2] and [4+3] cycloadditions between arylidenoxazolone systems and cyclopentadiene: a DFT analysis

The molecular mechanisms of the reactions between aryliden-5(4H)-oxazolone 1, and cyclopentadiene (Cp), in presence of Lewis acid (LA) catalyst to obtain the corresponding [4+2] and [4+3] cycloadducts are examined through density functional theory (DFT) calculations at the B3LYP/6-31G* level. The activation effect of LA catalyst can be reached by two ways, that is, interaction of LA either with carbonyl or carboxyl oxygen atoms of 1 to render [4+2] or [4+3] cycloadducts. The endo and exo [4+2] cycloadducts are formed through a highly asynchronous concerted mechanism associated to a Michael-type addition of Cp to the beta-conjugated position of alpha,beta-unsaturated carbonyl framework of 1. Coordination of LA catalyst to the carboxyl oxygen yields a highly functionalized compound, 3, through a domino reaction. For this process, the first reaction is a stepwise [4+3] cycloaddition which is initiated by a Friedel-Crafts-type addition of the electrophilically activated carbonyl group of 1 to Cp and subsequent cyclization of the corresponding zwitterionic intermediate to yield the corresponding [4+3] cycloadduct. The next rearrangement is the nucleophilic trapping of this cycloadduct by a second molecule of Cp to yield the final adduct 3. A new reaction pathway for the [4+3] cycloadditions emerges from the present study.     

Hetero Diels-Alder reactions of nitrosoamidines: an efficient method for the synthesis of functionalized guanidines

Hetero Diels-Alder reactions of transient nitrosoamidines are reported. Transient nitrosoamidines are formed by oxidation of protected N-hydroxylguanidines and are trapped in situ by 1,3-dienes to give [4 + 2] cycloadducts in good yields and regioselectivity. The resultant cycloadducts are versatile intermediates for the formation of functionalized guanidines. [reaction: see text]     

Catalytic enantioselective [2 + 4] and [2 + 2] cycloaddition reactions with propiolamides

We report here the catalytic and highly enantioselective [2 + 4] and [2 + 2] cycloaddition reactions of electron-rich dienes or silyl enol ethers with electron-deficient propiolamide derivatives induced by copper(II).3-(2-naphthyl)-L-alanine amide complex.     

Rh-catalyzed intermolecular and enantioselective [4 + 2] cycloaddition of 1,3-dienes with dimethyl acetylenedicarboxylate

A Rh-BINAP complex catalyzed an intermolecular and enantioselective [4 + 2] cycloaddition of 1-monosubstituted, 1,1- or 1,2-disubstituted buta-1,3-dienes with dimethyl acetylenedicarboxylate to give chiral cyclohexa-1,4-dienes.     

Dienophilic behavior of the vinylic (C=C) and the carbonyl (C=O) bonds of ketenes in reactions with 1,3-diazabuta-1,3-dienes

[reaction: see text] Ab initio and density functional studies (DFT) on cycloaddition reactions of 1,3-diazabuta-1,3-dienes with ketenes are reported. The vinylic (C=C) and the carbonyl (C=O) units of the ketenes are found to participate in concerted asynchronous [4 + 2] cycloaddition reactions. The transition states (3t, 4t, and 7t) for these paths have been located on the PE surface at the correlated levels of ab initio calculations. A reasonable mechanism for the formation of [4 + 2] and [2 + 2] adducts is presented.     

Theoretical evaluation of the origin of the regio- and stereoselectivity in the Diels-Alder reactions of dialkylvinylboranes: studies on the reactions of vinylborane, dimethylvinylborane, and vinyl-9-BBN with trans-piperylene and isoprene

Ab initio and DFT calculations have been performed to study the origin of the regio- and stereoselectivity of the Diels-Alder reactions of dialkylvinylboranes with substituted dienes. B3LYP/6-31G energies of the transition structures for the reactions of dimethylvinylborane and vinyl-9-BBN with trans-piperylene and isoprene yielded calculated ratios which are in very good agreement with experimental values. Nonclassical carbon-boron [4+3] secondary orbital interactions seem to account for the high endo stereoselectivity of these reactions. However, C-B interactions become less important when the bulkiness of the alkyl groups attached to boron increases. Both endo and exo transition structures for the reactions of dimethylvinylborane and vinyl-9-BBN adopt classical [4+2] character. This study also extends Singleton's investigation on butadiene to regioselectivity. FMO theory has been used to rationalize the lack of regioselectivity in the reactions of dimethylvinylborane. The anomalous meta regioselectivity of the Diels-Alder reaction of vinyl-9-BBN with trans-piperylene is mainly caused by steric effects.     

Nickel-catalyzed dehydrogenative [4 + 2] cycloaddition of 1,3-dienes with nitriles

Pyridines, which comprise one of the most important classes of the six-membered heterocyclic compounds, are widely distributed in nature, and the transition-metal-catalyzed [2 + 2 + 2] cycloaddition reaction of two alkynes and a nitrile is one of the most powerful methods for preparing versatile, highly substituted pyridine derivatives. However, the lack of chemo- and regioselectivity is still a crucial issue associated with fully intermolecular [2 + 2 + 2] cycloaddition. The present study developed the Ni(0)-catalyzed intermolecular dehydrogenative [4 + 2] cycloaddition reaction of 1,3-butadienes with nitriles to give a variety of pyridines regioselectively.     

"Formal" ruthenium-catalyzed [4+2+2] cycloaddition of 1,6-diynes to 1,3-dienes: formation of cyclooctatrienes vs vinylcyclohexadienes

[reaction: see text] A new "formal" Ru-catalyzed [4+2+2] cycloaddition of 1,6-diynes to 1,3-dienes giving conjugated 1,3,5-cyclooctatrienes and vinylcyclohexadienes is described. This formal cycloaddition is really a tandem process, the Ru(II)-catalyzed formation of (Z)-tetraenes or vinyl-(Z)-trienes followed by a pure thermal conrotatory 8 pi- or disrotatory 6 pi-electrocyclization. The proposed mechanism allows the differences in product ratio to be explained in terms of steric and stereochemical considerations.