Cycloaddition periselectivity

Cycloaddition reactions represent another important area of nitro olefin chemistry. Typically, nitroalkenes react in normal-electron-demand [4 + 2] cycloadditions as highly activated dienophiles (2ji-components) and produce nitro-substimted cyclohexenes [53]. However, under certain conditions nitroalkenes can switch the mode of reactivity in cycloadditions (periselectivity) and behave as electron-poor heterodienes (47i-components). Nitroalkenes react as 471-partners with electron-rich dienophiles under Lewis-acid activation [19], high pressure [54], and even thermal activation in some cases [55-57]. The products of such cycloadditions are six-membered cyclic nitronates (see Scheme 16.2, for example), whose properties will be discussed later in this text. 

Bis(tnfluoromethyl)-4,5-dihydrooxazin-6-ones [28] and their O-acetylated dcnvatives [96] are formed on treatment of acyl imines with acetyl chloride-hiethylamine at room temperature. The reaction was interpreted as a cycloaddition reaction involving a ketene [28] However, the periselectivity and regiochemistry of this reactwn-are not in agreement with results obtained from the reaction of... 

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)... 

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]... 

Thermally allowed [6 + 4] cycloadditions offer the attractive features of high stereoselectivity and rapid increase of molecular complexity. The limiting feature of many higher-order processes, however, is a lack of periselectivity that translates directly into the relatively low chemical yields of the desired cycloadducts. 

The periselectivity of the tropone-diene cycloaddition is dependent on the reaction temperature. The exo [6 + 4] cycloadduct is considered to be the kinetic product, the endo [4 + 2] cycloadduct being the thermodynamic product291. 

Such cycloadditions are dependent on the interactions of the azepine HOMO and the diene LUMO. Theoretical consideration of these orbitals reveals that bonding overlap is favourable for C-6—C-7 and C-4—C-5 additions and that, on the basis of secondary orbital interactions, the endo product is favored. Experimentally, however, it is found that additions are periselective and C-4—C-5 addition predominates in the cycloaddition of 1//-azepines with cyclopentadienones, isobenzofurans, tetra- and hexa-chlorocyclopentadienes, 1,2,4,5-tetrazines, a-pyrones and 3,4-diazacyclopentadienones (8lH(15)1569). 

It is frequent but not invariable that where a longer conjugated system has a geometrically accessible and symmetry-allowed transition structure like that in 5.90, the longer system is used. Thus, the [8+2] and [6+4] cycloadditions on pp. 15 16, and the [14+2] cycloaddition on p. 44 take place rather than perfectly reasonable Diels Alder reactions, and the 8-electron electrocyclic reactions of 4.51 and 4.54 takes place rather than disrotatory hexatriene-to-cyclohexadiene reactions. This kind of selectivity is called periselectivity. 

Acenaphthylene, indene, and styrene undergo periselective 4 + 2-cycloaddition with 3-ethoxycarbonyl-2//-cyclohepta[Z>]furan-2-one in high yield.152... 

Abstract The main computational studies on the formation of (3-lactams through [2+2] cycloadditions published during 1992-2008 are reported with special emphasis on the mechanistic and selectivity aspects of these reactions. Disconnection of the N1-C2 and C3-C4 bonds of the azetidin-2-one ring leads to the reaction between ketenes and imines. Computational and experimental results point to a stepwise mechanism for this reaction. The first step consists of a nucleophilic attack of the iminic nitrogen on the sp-hybridized carbon atom of the ketene. The zwitterionic intermediate thus formed yields the corresponding (3-1 actant by means of a four-electron conrotatoty electrocyclization. The steroecontrol and the periselectivity of the reaction support this two-step mechanism. The [2+2] cycloaddition between isocyanates and alkenes takes place via a concerted (but asynchronous) mechanism that can be interpreted in terms of a [n2s + (n2s + n2s)] interaction between both reactants. Both the regio and the stereochemistry observed are compatible with this computational model. However, the combination of solvent and substituent effects can result in a stepwise mechanism. 

Herndon and co-workers4 developed a model for predicting regioselectivity which has been adapted to periselectivity problems by Paddon-Row.64 It makes two assumptions (a) the two reaction partners approach in parallel planes and (b) the distance between these planes is the same in all reactions. The second is a serious constraint, which explains a success rate of 14 correct predictions out of 17 cases (82%). The model is more reasonable when applied to regioselectivity, where two different orientations of the same cycloaddition are compared (122 correct predicttions in 133 cases, i.e. 91.7%).5 Nonetheless, to the best of our knowledge, FO theory provides the only simple way to study periselectivity available at present. 

Another example of cycloaddition selectivity was observed for the reaction of cyclopentadiene with diphenylketene (Equation (37)). Originally only products of [2+2] cycloaddition were observed and these reactions were considered as highly periselective. 

Numerous [3 + 2] cycloaddition reactions have been performed with bis(trifluoromethyl)-substituted azomethine imines (79CB2609,79LAI33). Noteworthy is the [3 + 2] cycloaddition reaction with tetracyanoethylene, which adds across one of the nitrile functions instead of adding across the CC double bond. This is one of the rare examples of this type of periselectivity found in the case of tetracyanoethylene in [3 + 2] cycloaddition processes (76LA30). 

The dependence of the periselectivity on the relative redox potentials of the reaction partners has been studied for the case of the electron-rich dienophiles 36a-e and 13b with the acyclic diene 35, shown in Scheme 4.10. While the corresponding neutral reaction is not observed, ET efficiently catalyzes this cycloaddition. Table 4.5 shows that [2 + 2] selectivity dominates the reaction when incorporating dienophiles with oxidation potentials higher than that of 35 (1.36 eV). In these cases, the reaction will proceed via oxidation of 35. [4 + 2] addition to acychc dienes, which... 

The periselectivity of the reaction of a given diene with tropone is critically dependent on temperature. The variable course of the cycloaddition of ( )-l-trimethylsilyloxybutadiene with tropone as a function of reaction temperature is a Carnatic illustration of this phenomenon. At 80 C the major adduct is bicy-clo[4.4.1]undecenone (10), whereas in refluxing xylene the [4 + 2] cycloadduct (11) prevails as a mixture of regioisomers. A further example of the dichotomy between [6 + 4] and [4 + 2] reaction pathways can be seen with (Z)-l-acetoxybutadiene, which provides some [6 + 4] cycloadduct along with larger quantities of various [4 -i- 2] pr ucts as depicted in equation (1). In contrast to these results, dienes such as ethyl 2,4-hexadienoate and furan do not yield any [6 + 4] or [4 2] products when heated with tropone. The latter result, in particular, may be reflective of the reversibility of the furan cycloadducts. Various furan derivatives do provide modest yields of mixtures of endo and exo [4 + 2] cycloadducts with tropone when reacted together at 3 kbar and 130 C. ... 

The variations of periselectivity exhibited in the cycloadditions of fulvenes to dienes have been rationalized by rqjplication of frontier molecular orbital theory. The fulvene orbitals of interest in these reactions are depicted in Figure 2. - The controlling orbitals in the reaction of fulvene with an... 

Cycloheptatriene and related heterocyclic analogs have been examined to some extent with regard to their reactivity with various conjugated diene partners. Characteristically, higher-order cycloaddition pathways often suffer relative to alternative modes of reaction in these systems and usually a select type of highly reactive diene partner is a prerequisite for viable cycloaddition to occur. Selectivity in these species can also be compromised by die intervention of the corresponding norcaradiene tautomer in certain circumstances. Moctest periselectivity coupled with low chemical yields limit the potential synthetic utility of these cycloadditions. 

Heating TV-ethoxycarbonylazepine with the electron-deficient diene (96) provided [2 + 4] adduct (97) and [6 -i- 4] adduct (90) in nearly equal quantities. Other examples of relatively low conversion [6 + 4] cycloadditions of substituted azepines and various dienes have been reported but are of little synthetic consequence due to low periselectivity and modest chemical yields. - Oxepin heterocycles display a range of reactions with dienes which are similar in scope to the azepine series and, as such, will not be dealt with specifically in this review. Other cyclic polyenes such as cyclooctatetraene are known to yield some [6 + 4] adducts when exposed to highly reactive diene species. For example, the potent electron-deficient diene 2,S-dimethoxycarbonyl-3,4-diphenylcyclopent ienone gives a modest amount of the corresponding [6 -I- 4] cycloadduct when reacted with cyclooctatetraene. ... 

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