Dienophiles reactivity

Although one trifluoromethyl group activates an alkene as a dienophile, two or more can actually inhibit dienophilic reactivity, as evidenced by the fact that... 

Similarly, partially fluorinated and perfluorinated methylenecyclopropanes [57, 52], cyclopropenes [55, 84, 55], cyclobutenes [75, 56], and bicychc alkenes [57, 55, 59, 90] apparently denve dienophilic reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [244] cycloadditions [57, 52] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [24-2] cycloadditions [57]... 

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)... 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

The optically active a-sulfinyl vinylphosphonate 122 prepared in two different ways (Scheme 38) is an interesting reagent for asymmetric synthesis [80]. This substrate is an asymmetric dienophile and Michael acceptor [80a]. In the Diels-Alder reaction with cyclopentadiene leading to 123, the endo/exo selectivity and the asymmetry induced by the sulfinyl group have been examined in various experimental conditions. The influence of Lewis acid catalysts (which also increase the dienophilic reactivity) appears to be important. The 1,4-addition of ethanethiol gives 124 with a moderate diastereoselectivity. 

MCP (1) is not known to undergo [4 + 2] cycloadditions. The substitution of two, or more, ring protons with fluorine atoms, however, seems to improve dramatically the dienophilic reactivity of the exocyclic double bond. 2,2-Di-fluoromethylenecyclopropane (5) is a quite reactive dienophile in Diels-Alder cycloadditions. With cyclopentadiene (6) and furan (7), it formed two isomeric adducts (Scheme 1) [9]. In both cases the adduct with the endo CF2 group is the major isomer. 

In a comparative study, Jacobson et al. have shown that for the cis-fused cyclohexadiene, l,2,3,4,4a,8a-hexahydronaphthalene, the dienophilic reactivity follows the order PTAD > cis-DEAZD > trans-DEAZD, while the order is reversed for their reactivity as enophiles.67 Other studies have produced similar conclusions.21,54 In general, azo compounds give more ene product than the corresponding C=C compounds. 

This indicates that the dienophilic reactivity of singlet oxygen surpasses the other two modes of reaction (formation of hydroperoxides and 1,2-dioxetanes). 

Phosphaalkenes that possess a X3a2-phosphorus atom can be isolated when appropriately substituted (151). These systems exhibit a much more expressed dipolarophilic than dienophilic reactivity, probably as a consequence of the polarity of the P=C bond. The [3 + 2] cycloaddition of diazo compounds with phosphaalkenes 87 leads to 4,5-dihydro-3//-1,2,4-diazaphospholes 88 (Scheme 8.21) that are not always isolated. Quite often, elimination of molecular nitrogen occurs during the cycloaddition at or below 20 °C. In other cases, N2 extrusion is achieved at... 

We focused on 3-cyanochromone derivatives, for the dienophilic reactivity of these compounds has gone unnoticed.18 In addition, these 3-cyanochromones could serve as excellent model systems for exploring the potential of our strategy and investigating the scope [i.e. regio- and stereoselectivity] of y-pyrones in [4 + 2] cycloadditions. As a result, this cycloaddition also became a subject of research by other groups.19... 

It was shown that the diene reacted only slowly with tetracyanoethylene, even slower than with maleic anhydride. The reaction of the ortho adduct with maleic anhydride led to the same 1 2 adduct as the photochemical reaction between benzene and maleic anhydride. The previous failure to trap the diene with tetracyanoethylene resulted from an unexpectedly low dienophilic reactivity of this compound toward the ortho adduct in the presence of benzene. Tetracyanoethylene is apparently completely complexed in benzene solution. 

From the above results it can be inferred that sulfinyl ethylenes are not good dienophiles because of their low reactivity and poor stereoselectivity. In order to improve both of these factors, different electron-withdrawing groups (able to increase dienophilic reactivity and to restrict conformational movement around the C-S bond, thus improving the stereoselectivity) were incorporated into the double bond. They are presented in the sections below, classified according to the number and kind of the additional activating groups present in the vinyl sulfoxide moiety. 

The introduction of an electron-withdrawing group (N02 or CF3) at the pyridine ring of 2-pyridyl sulfoxides enhances the dienophilic reactivity. The results obtained from racemic dienophiles ( )-14, ( )-25, and ( )-26 with furan are shown in Scheme 12 [41]. The reactions took place with moderate endo/exo selectivity in all cases but the 7r-facial selectivity was quite high (for both endo and exo approaches) when substituted pyridines 25 and 26 were used as dienophiles. 

Racemic diesters 82 (Scheme 42), containing the bis-sulfoxide moiety incorporated into a five-membered ring, have also been used as dialkoxycarbonyl ketene equivalents [82]. They react with cyclopentadiene in 7-12 h at room temperature, affording mixtures of two adducts. The relative configuration of 82 was not unequivocally determined, but it was speculatively assigned on the basis of the conformational preferences of the precursor monosulfoxide and the presumably favored steric course of its MCPBA oxidation. We must point out the unexpectedly similar reactivity of dienophiles 80 and 82, which is very difficult to explain given the increase in the dienophilic reactivity that two ester groups usually induce in ethylenic systems. 

From a mechanistic perspective, we think that one of the most striking aspects of these reactions is the influence of the sulfinyl group on the reactivity of the sulfinylated substrates. According to Hammet a-values, the SOR group must be considered as an efficient electron-withdrawing group. Nevertheless, its influence in dienophilic reactivity is rather low. It can be inferred from the fact... 

The last problem associated with the use of the sulfinyl group as a chiral inductor in cycloaddition reactions is related to the endo/exo reactivity. From the available data, the endo directing power of the sulfinyl group is not large. The need to incorporate other functional groups into vinyl sulfoxides, thus increasing their dienophilic reactivity, decrees that the formation of mixtures is difficult to avoid in many cases as a consequence of the competition between the... 

The chemical reactivity of (1) and (2) is a dichotomy. Benzenoid character is indicated in normal electrophilic substitution (nitration, sulfonation and catalyzed halogenation, Section 4.26.4.1) and in the lack of dienophile reactivity in the Diels-Alder reaction. On the other hand, typical dienoid character is exhibited in the facile ozonolysis of the benzene ring of (1) and in the easy, non-catalyzed tetra-addition of halogen (see Section 4.26.4.1). 

As can be seen in Equation (170), the dienophilic reactivity of the double bond in l,4-epoxy-l,4-dihydronaphtha-lenes can further be illustrated by its reaction with bisepoxide 281, leading to the formation of the structurally intriguing 282 and 283 in 34% and 44% yield, respectively <2001T571>. 

Diene Reactivity Dienophile Reactivity Intra Molecular Diels-Alder Reactions... 

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