Peri-selective photocycloadditions of methyl 2-pyrone-5-carboxylate with unsaturated cyclic ethers

Photosensitized cycloaddition reaction of methyl 2-pyrone-5-carboxylate ( 1 ) with 2,3-dihydrofuran gave cis- exo- and cis-endo-[2 + 2] cycloadducts across the C₃-C₄ double bond in 1 , and a [4 + 2] cycloadduct which was different in addition-orientation from the Diels-Alder adducts. Each [2 + 2] cycloadduct was obtained by the use of sensitizers having different triplet energies. Photosensitized reactions of 1 with 3,4-dihydro-2H-pyrans afforded cis-endo-[2 + 2] cycloadducts, respectively. The photocycloaddition mechanism was also explained from the excited state of 1 calculated by means of MNDO-Cl method.     

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.     

Diels-Alder-Reaktion eines elektronenarmen C-Acylimins mit Tetraethoxyethylen

Summary The synthesis of two C-acylimines and their reactivity towards electron rich dienophiles inDiels-Alder reactions is described. A [4+2] cycloadduct is obtained only in one case: from the reaction of a C-acylimine substituted by two methoxycarbonyl groups with tetraethoxyethylene. No [2+2] cycloadducts are observed.

     

Nitrene insertion reactions. 1. Dimethyl N-carbethoxyazepines and their cycloaddition reaction products

Dimethyl-N-carbethoxyazepines, isolated from the reaction between ethyl azidoformate and o-, m- and p-xylenes, react with tetracyanoethylene to give [4 + 2] Diels-Alder adducts. Nitroso-benzene is inert toward 2-methylazepines, but reacts with 3,6-dimethyl-N-carbethoxyazepine to give a [6 + 2] cycloadduct. The effect of two methyl substituents on the course of the cycloaddition reactions is discussed.     

A novel and facile stereocontrolled synthetic method for polyhydro-quinolines and pyridopyridazines via a diene-transmissive Diels-Alder reaction involving inverse electron-demand hetero Diels-Alder cycloaddition of cross-conjugated azatrienes

Cross-conjugated azatrienes bearing an electron-withdrawing sulfonyl or benzoyl group on the nitrogen atom underwent, on heating or in the presence of a Lewis acid (TMSOTf), an initial inverse electron-demand hetero Diels-Alder reaction with electron-rich dienophiles (vinyl ether, vinyl thioether, and allenyl ether) to produce 1:1 cycloadducts with high endo selectivity. The initial cycloadducts thus obtained underwent a second Diels-Alder reaction stereoselectively on the newly formed diene unit with electron-deficient dienophiles to give the crossed bis-cycloadducts, octahydroquinolines, with high diastereo-π-facial selectivity. The N-sulfonylazatrienes tethering an ortho-cinnamyloxyphenyl dienophile at the triene terminal underwent an initial intramolecular hetero Diels-Alder reaction of the inverse electron-demand type. The subsequent second Diels-Alder reaction of the formed mono-cycloadducts completed the diene-transmissive hetero Diels-Alder protocol to give benzopyrano[3,4-c]quinolines in a highly stereoselective manner.     

Reaction of carboryne with styrene and its derivatives

Reaction of carboryne generated from 1-I-2-Li-1,2-C₂B₁₀H₁₀ with styrene and its derivatives has been studied. In addition to [2+2] cycloaddition reaction and/or ene reaction, an extra-annular [4+2] cycloaddition reaction is also observed, depending upon the substituents on the vinyl unit. The resulting [4+2] cycloaddition intermediates are so reactive that they immediately undergo rearomatization via either a formal 1,3-hydrogen rearrangement or dehydrogenation initiated by hydrogen abstraction with carboryne in biradical form, to give 3,4-dihydronaphtho[1,2]-o-carboranes and naphtho[1,2]-o-carboranes, respectively. In sharp contrast to that of benzyne, further additions of carboryne onto the primary cycloadducts are not observed.     

Evaluation of ethyl 2-carbomethoxyethenesulfinates as 2-hydroxymethyl enethiol equivalents in the Diels-Alder reaction

Z- and E-ethyl 2-carbomethoxyethenesulfinates 1 and 2 hold the potential to be enethiol equivalents by way of Diels-Alder cycloaddition chemistry followed by reduction. To pursue this, both dieneophiles were subjected to thermal and Lewis acid mediated [4+2] cycloadditions with a number of dienes. Yields of cycloadduct ranged from 34 to 94%, with cycloadditions of the aromatic dienes proceeding in moderate yields, presumably due to the reversibility of the reactions. Many cycloadducts were obtained as a mixture of sulfur epimers, but these isomers were unified in the subsequent reduction step. Using either LAH or DIBAL, the cycloadducts were reduced providing β-mercapto (or sulfanyl) carbinols in 32-97%. The sequence of two reactions places sulfur and hydroxy functional groups in set relative stereochemistry within a 6-membered ring.     

New synthetic approach to α-fluoro-β-arylvinyl sulfones and their application in Diels-Alder reactions

A new pathway towards α-fluoro-β-arylvinyl sulfones was elaborated. The reaction of β-bromo-β-fluorostyrenes with sodium 4-methylphenylsulfinate proceeds with maximum 94:6 stereoselectivity and 72-90% yields. The formed α-fluoro-β-arylvinyl sulfones were found to be good dienophiles for Diels-Alder reactions with simple 1,3-dienes. From corresponding (E)-configured dienophiles and cyclopentadiene, cycloadducts bearing the fluorine substituent in exo-position were formed predominantly, while with diphenylisobenzofuran the products with endo-orientation of the fluorine were obtained as the major products. From these cycloadducts, as a proof of principle, p-toluenesulfinic acid was eliminated to give 2-fluoro-3-(4-nitrophenyl)norbornadiene, the formal [4+2]-cycloadduct of cyclopentadiene and 1-fluoro-2-(4-nitrophenyl)acetylene, or the corresponding diphenylisobenzofuran cycloadducts, respectively. This reaction was not successful when other β-hydrogen atoms are accessible for elimination.     

Dynamic effects on the periselectivity, rate, isotope effects, and mechanism of cycloadditions of ketenes with cyclopentadiene

The cycloadditions of cyclopentadiene with diphenylketene and dichloroketene are studied by a combination of kinetic and product studies, kinetic isotope effects, standard theoretical calculations, and trajectory calculations. In contrast to recent reports, the reaction of cyclopentadiene with diphenylketene affords both [4 + 2] and [2 + 2] cycloadducts directly. This is surprising, since there is only one low-energy transition structure for adduct formation in mPW1K calculations, but quasiclassical trajectories started from this single transition structure afford both [4 + 2] and [2 + 2] products. The dichloroketene reaction is finely balanced between [4 + 2] and [2 + 2] cycloaddition modes in mPW1K calculations, as the minimum-energy path (MEP) leads to different products depending on the basis set. The MEP is misleading in predicting a single product, as trajectory studies for the dichloroketene reaction predict that both [4 + 2] and [2 + 2] products should be formed. The periselectivity does not reflect transition state orbital interactions. The (13)C isotope effects for the dichloroketene reaction are well-predicted from the mPW1K/6-31+G** transition structure. However, the isotope effects for the diphenylketene reaction are not predictable from the cycloaddition transition structure and transition state theory. The isotope effects also appear inconsistent with kinetic observations, but the trajectory studies evince that nonstatistical recrossing can reconcile the apparently contradictory observations. B3LYP calculations predict a shallow intermediate on the energy surface, but trajectory studies suggest that the differing B3LYP and mPW1K surfaces do not result in qualitatively differing mechanisms. Overall, an understanding of the products, rates, selectivities, isotope effects, and mechanism in these reactions requires the explicit consideration of dynamic trajectories.     

Electrocyclic Reactions of Siloles: A Combined Experimental and Theoretical Study

The reaction of 4‐chloro‐1,2‐dimethyl‐4‐supersilylsila‐1‐cyclopentene ( 2 a ) with Li[NiPr₂] at ?78 °C results in the formation of the formal 1,4‐addition product of the silacyclopentadiene derivative 3,4‐dimethyl‐1‐supersilylsila‐1,3‐cyclopentadiene ( 4 a ) with 2,3‐dimethyl‐4‐supersilylsila‐1,3‐cyclopentadiene ( 5 a ). In addition the respective adducts of the Diels–Alder reactions of 4 a + 4 a and 4 a + 5 a were obtained. Compound 4 a , which displays an s‐cis‐silacyclopentadiene configuration, reacts with cyclohexene to form the racemate of the [4+2] cycloadduct of 4 a and cyclohexene ( 9 ). In the reaction between 4 a and 2,3‐dimethylbutadiene, however, 4 a acted as silene as well as silacyclopentadiene to yield the [2+4] and [4+2] cycloadducts 10 and 11 , respectively. The constitutions of 9 , 10 , and 11 were confirmed by NMR spectroscopy and their crystal structures were determined. Reaction of 4‐chloro‐1,2‐dimethyl‐4‐tert‐butyl‐4‐silacyclopent‐1‐ene ( 2 c ) with KC₈ yielded the corresponding disilane ( 12 ), which was characterized by X‐ray crystal structure analysis (triclinic, P$\bar 1$ ). DFT calculations are used to unveil the mechanistic scenario underlying the observed reactivity.     

A new entry to the synthesis of substituted azetidines: [2+2] cycloaddition reaction of four-membered endocyclic enamides to ketenes

The first example of a [2+2] cycloaddition reaction of a four-membered endocyclic enamide (2-azetine) to dichloroketene is described and constitutes a new entry to the synthesis of substituted azetidines. Preliminary studies concerning the Baeyer-Villiger oxidation of the [2+2] cycloadduct revealed an unusual regioselectivity. The synthesis of a new azetidine-3-carboxylic acid derivative from the [2+2] cycloadduct is also presented.     

Quantum mechanical inspection of the Diels-Alder approach to biaryls mechanism

The Diels-Alder reaction of substituted cyclohexadienes with substituted phenylacetylenes offers an attractive alternative for the synthesis of biaryl compounds via a two-step cycloaddition/cycloelimination pathway. Quantum mechanical calculations using B3LYP and M06-2X density functional methods for the reaction of 2-chloro-6-nitrophenylacetylene with 1-carbomethoxy-cyclohexadiene show the reaction proceeds by a stepwise diradical [4+2] cycloaddition followed by concerted [2+4] cycloelimination of ethylene. [2+2] cycloadducts are also the result of stepwise addition. [2+2] cycloadducts isomerize to [4+2] cycloadducts via diradical pathways, which involve the same diradical intermediate in cycloaddition. There is also a competitive conrotatory ring opening followed by trans-cis double bond isomerization pathway of the [4.2.0] bicycle (the [2+2] cycloadduct) to give the cis,cis,cis-1,3,5-cyclooctatriene.     

Site-selective photocycloadditions of 2-pyrones with electron-poor olefins and the derivation from the cycloadducts

Photosensitized cycloaddition of 4,6-dimethyl-2-pyrone ( 1 ) with methacrylonitrile ( 3b ) afforded two types of [2 + 2]cycloadducts, 4b and 6b , across the C₅-C₆ and C₃-C₄ double bonds in 1 , respectively. Photosensitized reactions of 1 with dimethyl maleate and dimethyl cyclobutene-1,2-dicarboxylate gave [2 + 2]cycload-ducts 4d, 4e across the C₅-C₆ double bond, in addition to [4 + 2]cycloadduct 9d or bicyclo[4.2.0]octadiene 10e . The photoreactions of methyl 2-pyrone-5-carboxylate ( 2 ) with 3b and 2-chloroacrylonitrile ( 3c ) gave [4 + 2]cycloadducts 5b, 5c in addition to [2 + 2]cycloadducts 11b and 11c across the C₅-C₆ double bond in 2 . The photocycloaddition mechanism was explained from results calculated by means of PM3-CI method. Namely, the site- and/or regio-selective products, 4, 5, 8, 9 and 10 were thought to come from the same site-selective radical intermediates in the case of electron-poor olefins. Pyrolysis and/or hydrolysis of the cycload-ducts 4e, 5b, 5c gave 5,6-dihydro-2-pyrone 12 or benzene derivatives.     

[2 + 2] Cycloaddition reactions of unsymmetrically substituted carbodiimides

N-Alkyl-N′-arylcarbodiimides add alkyl and aryl isocyanates to the N-alkyl substituted CN double bond to yield 4-arylimino-1,3-diazetidine-2-ones 3. In the case of bulky alkyl substituents the reaction still proceeds across the sterically hindered CN double bond. N-Aryl-N′-[(4-dimethylamino)phenyl]carbodiimides form [2 + 2] cycloadducts with aryl isocyanates preferentially across the CN double bond not attached to the electron-rich aryl groups. However, steric crowding on this CN double bond directs the reaction to the adjacent double bond of the heterocumulative system. The rate of the [2 + 2] cycloaddition reaction of N'-methyl-N′-phenylcarbodiimide with 4-nitrophenylisocyanate is about 2.5 times faster in acetonitrile than in benzene.     

Diastereoselectivity-Switchable Gold-Catalyzed Formal [3+2]-Cycloadditions of N-2,2,2-Trifluoroethylisatin Ketimines with Yne−Enones

The unexpected gold-catalyzed formal [3+2]-cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with 2-(1-Alkynyl)-2-alken-1-ones is reported. Both diastereomers of the corresponding cycloadducts were formed in moderate to excellent yields with excellent diastereoselectivities by switching the catalytic system from mono-gold to gold/silver bimetallic catalytic system. The practicality of this protocol is demonstrated by scale-up reaction and the transformations of the cycloadduct.     

Reactions of acceptor substituted thiophene-1,1-dioxides with cyclopentadiene: control of selectivity by substitution

Diels-Alder reactions of thiophene-1,1-dioxides with strong electron withdrawing groups (EWG) were studied experimentally and theoretically. Thiophene-1,1-dioxides with two strong EWG behave as dienophiles and regio- and stereoselectively react with cyclopentadiene to give [2+4] cycloadducts 2a-c, which are derivatives of benzothiophene. In contrast, thiophene-1,1-dioxides with one EWG behave as dienes in the inverse electron demand Diels-Alder reaction yielding dihydro-1H-indenes derivatives. Cope [3,3]-sigmatropic rearrangement of adducts 2a-c was also demonstrated. MP2 calculations successfully rationalize the contrasting regioselectivities of these cycloaddition reactions.     

Enantioselective [4+2] cycloaddition of ketenes and 9,10-phenanthrenequinone catalyzed by N-heterocyclic carbenes

Chiral N-heterocyclic carbenes were found to be efficient catalysts for the formal [4+2] cycloaddition reaction of alkyl(aryl)ketenes and 9,10-phenanthrenequinone to give the corresponding cycloadducts in good yields with high enantioselectivities.     

Addition reactions of cyclooctatetraene with 1,3-diphenylisobenzofuran the benzene ring as dienophile in a [4+2] cycloaddition reaction

Addition reactions of cyclooctatetraene with 1,3-diphenylisobenzofuran resulted in the formation of three 1:1 cycloadducts, 1, 2, and 3, and a 1:2 cycloadduct, 4. Single crystal x-ray analysis established 3 to be a cage compound formed by an unprecedented [4+2] cycloaddition reaction of 1 in which the double bond of the benzene moiety acted as the dienophile.     

Unexpectedly cyclized products by reaction of N-tosyliminoisoquinolinium ylides with trimethylsilylketene

The reaction of N-tosyliminoisoquinolinium ylides with trimethylsilylketene as a C2 unit introducing reagent, giving unexpected [3+2] cycloadducts, pyrazolo[5,1-a]isoquinolines, is described.     

Photoreactions of β-aziridinylacrylonitriles and acrylates with alkenes: formation of head-to-head adducts and application to the preparation of pyrrolizidine alkaloid

The photochemical C,C-bond cleavage of N-benzyl β-aziridinylacrylonitrile 1 and acrylate 2 and the subsequent [3+2] cycloaddition with electron-deficient alkenes afforded head-to-head adducts selectively and efficiently. Irradiation of N-phenyl aziridine 3 with acrylonitrile gave adducts, but photoreaction of N-benzoyl aziridine 4 and thermal reactions of 3 and 4 with alkenes yielded C(γ),N-cleaved products instead of cycloadducts. N-trityl aziridine 5 also reacted with electron-deficient alkenes, affording 2,3-cis-pyrrolidine derivatives exclusively. A formal synthesis of a pyrrolizidine alkaloid, isoretronecanol (27), starting from 5 was achieved in a convenient manner.