Cycloaddition reactions bonds

Sulfonium ylides may be added to C N double bonds to yield aziridines in a formal [1 -t-2]-cycloaddition. Alkyl azides are decomposed upon heating or irradiating to yield ni-trenes, which may also undergo [ 1 + 2 -cycloaddition reactions to yield highly strained hetero-cycles (A.G. Hortmann, 1972). 

Isocyanates are Hquids or soHds which are highly reactive and undergo addition reactions across the C=N double bond of the NCO group. Reactions with alcohols, carboxyUc acids, and amines have been widely exploited ia developiag a variety of commercial products. Cycloaddition reactions involving both the C=N and the C=0 double bond of the NCO group have been extensively studied and used for product development (1 9). 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

The different possibilities for the creation of the pyrazole ring according to the bonds formed are shown in Scheme 46. It should be noted that this customary classification lacks mechanistic significance actually, only two procedures have mechanistic implications the formation of one bond, and the simultaneous formation of two bonds in cycloaddition reactions (disregarding the problem of the synchronous vs. non-synchronous mechanism). 

Isothiazole-4,5-dicarboxylic acid, 3-phenyl-dimethyl ester synthesis, S, 150 Isothiazole-5-glyoxylic acid ethyl ester reduction, 6, 156 Isothiazole-4-mercurioacetate reactions, 6, 164 Isothiazole-5-mercurioacetate reactions, 6, 164 Isothiazoles, 6, I3I-I75 acidity, 6, 141 alkylation, 6, 148 aromaticity, S, 32 6, 144-145 basicity, 6, I4I biological activity, 6, 175 boiling points, 6, I43-I44, 144 bond fixation, 6, 145 bond orders, 6, I32-I34 calculated, 6, 133 bromination, S, 58 6, 147 charge densities, 6, 132-134 cycloaddition reactions, 6, 152 desulfurization, S, 75 6, 152 deuteration, S, 70... 

Oxepin, 4-ethoxycarbonyl-2,3,6,7-tetrahydro-synthesis, 7, 578 Oxepin, 2-methyl-enthalpy of isomerization, 7, 555 Oxepin, 2,3,4,5-tetrahydro-reduction, 7, 563 synthesis, 7, 578 Oxepin, 2,3,4,7-tetrahydro-synthesis, 7, 578 Oxepin, 2,3,6,7-tetrahydro-oxidation, 7, 563 reduction, 7, 563 Oxepin-2,6-dicarboxylic acid stability, 7, 565 Oxepinium ions synthesis, 7, 559 Oxepins, 7, 547-592 antiaromaticity, 4, 535 applications, 7, 590-591 aromatization, 7, 566 bond lengths and angles, 7, 550, 551 cycloaddition reactions, 7, 27, 569 deoxygenation, 7, 570 dipole moment, 7, 553 disubstituted synthesis, 7, 584... 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

When the orbitals have been classified with respect to symmetry, they can be arranged according to energy and the correlation lines can be drawn as in Fig. 11.10. From the orbital correlation diagram, it can be concluded that the thermal concerted cycloadditon reaction between butadiene and ethylene is allowed. All bonding levels of the reactants correlate with product ground-state orbitals. Extension of orbital correlation analysis to cycloaddition reactions involving other numbers of n electrons leads to the conclusion that the suprafacial-suprafacial addition is allowed for systems with 4n + 2 n electrons but forbidden for systems with 4n 7t electrons. 

Perfluoroalkyl groups adjacent to multiple bond systems lower the frontier molecular orbitals (FMOs) Therefore, cycloaddition reactions preferentially occur with electron-rich multiple-bond systems The preference of bis(trifluoromethyl)-substituted hetero-l,3-dienes for polar reacuons makes them excellent model compounds for developing new types of diene reactions deviating from the well documented Diels-Alder scheme (pathway 1) A systematic study of the reactions of diene (1 =2-3=4)-dienophile (5=6) combinations reveals new synthetic possibilities that have not yet been fully exploited as tools for preparative organic cherrustry (equation 25)... 

The first example of a cycloaddition reaction of a multiple bond to a diene was reported in 1917 Surprisingly, it was found that benzal azine adds to 2 equivalents of several unsaturated systems, when offered in excess, to yield bicyclie compounds. This reaction was named criss-cross" cycloaddition [190], Exploitation of the preparative potential of criss-cross cycloaddition began only in the early 1970s, when hexafluoroacetone azine became available on a larger scale [191,192] The study of this reaction proved to be an impetus tor the development of azine chemistry [183, 193]... 

The azomethine imines exhibit the typical cycloaddition behavior expected of 1,3-dipolar species [fSJ] Numerous [3+2] cycloaddition reactions have been performed [201 204] Tetracyanoethylene adds to azomethine imines across the nitnle function instead of the C=C double bond This reaction is a rare example of this type of periselectivity [208] (equation 47)... 

Polyfluoroalkyl- and Perfluoroalkyl-Substituted CO and CN Multiple Bonds as Dienophiles in [4+2] Cycloaddition Reactions... 

One of the features of Diels-Alder reactions with most alkyl and aryl nitriles that has made them rather unattractive as dienophiles is the requirement of very high reaction temperatures Again, only when electron-withdrawing substituents are directly bonded to the nitnle function do [4+2] cycloaddition reactions occur at reasonably low temperatures [ 48, 231, 232] A high yield [4+2] cycloaddition was observed on reaction of 4,4-bis(trifluoromethyl) 1 thia-3-aza-l,3-butadienes with trifluoroacetonitrile at 150 °C [225]... 

Cycloaddition reactions where bis(trifluoromethyl)-substituted hetero-1,3-dienes act as dienophiles have been descnbed for open-chain and cyclic dienes [115, 126, 127] The balance of the diene -dienophile activity of bis(tnfluoro-methyl)-substituted hetero-l,3-dienes can be influenced strongly by the substituents bonded to the inuno nitrogen atom For instance, A/-(arylsulfonyl) denvatives of tnfluoroacetaldimine and hexafluoroacetone imine do not act as dienes but exhibit only the dienophile reactivity of electron deficient imines [5 229, 234,235, 236 237] (equation 52)... 

The reactions of bis(trifluoromethyl)-subsatuted hetero 1,3 dienes are predomi nantly LLJMO controlled processes [238] With polar or highly polarizable dieno philes, the tendency to undergo stepwise cycloaddition reactions is considerable Notably these hetero-1,3-dienes react with a,(l unsaturated hetero multiple bond systems across the hetero multiple bond exclusively [243, 246 248] (equation 53)... 

In contrast, when ot,P-unsaturated multiple bond systems act as dienophiles in concerted [4+2] cycloaddition reactions, they react across the C=C double bond Periselectivity as well as regiochemistry are explained on the basis of the size of the orbital coefficients and the resonance integrals [25S]... 

Most of the reactions described in this chapter would fall under Huisgen s definition of a cycloaddition reaction (/, la). However some of the reactions described would not be considered cycloaddition reactions according to this restrictive definition. Therefore, the more liberal definition given by Baldwin will be used as a guideline, namely, Cycloadditions are chemical transformations giving at least one product having at least two new bonds as... 

Terminal alkynes with no electron-withdrawing group next to the acetylenic linkage when treated with enamines merely add across the double bonds of the enamines (9i). But electrophilic alkynes (those with an electron-withdrawing group next to the acetylenic linkage) undergo cycloaddition reactions with enamines. 

The reaction course of the cycloaddition reaction can also be dependent on the Lewis acid complex used as the catalyst. When the substrate contains an allylic C-H bond, both a cycloaddition and an ene reaction can occur. In the reaction of glyoxylate 4 with 2,3-dimethyl-l,3-butadiene 5 both the cycloaddition product 6... 

In an investigation by Yamabe et al. [9] of the fine tuning of the [4-1-2] and [2-1-4] cycloaddition reaction of acrolein with butadiene catalyzed by BF3 and AICI3 using a larger basis set and more sophisticated calculations, the different reaction paths were also studied. The activation energy for the uncatalyzed reaction were calculated to be 17.52 and 16.80 kcal mol for the exo and endo transition states, respectively, and is close to the experimental values for s-trans-acrolein. For the BF3-catalyzed reaction the transition-state energies were calculated to be 10.87 and 6.09 kcal mol , for the exo- and endo-reaction paths, respectively [9]. The calculated transition-state structures for this reaction are very asynchronous and similar to those obtained by Houk et al. The endo-reaction path for the BF3-catalyzed reaction indicates that an inverse electron-demand C3-0 bond formation (2.635 A... 

Huisgen has reported in 1963 about a systematic treatment of the 1,3-dipolar cycloaddition reaction as a general principle for the construction of five-membered heterocycles. This reaction is the addition of a 1,3-dipolar species 1 to a multiple bond, e. g. a double bond 2 the resulting product is a heterocyclic compound 3. The 1,3-dipolar species can consist of carbon, nitrogen and oxygen atoms (seldom sulfur) in various combinations, and has four non-dienic r-electrons. The 1,3-dipolar cycloaddition is thus An +2n cycloaddition reaction, as is the Diels-Alder reaction. 

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