Polar stepwise 2 + 2-cycloaddition

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)... 

Benzylideneeyclopropane (156) and diphenylmethylenecyclopropane (157) reacted rapidly with TCNE to afford 159 and 160, respectively, in good yields. Since the reaction rate is highly dependent on the solvent polarity, the cycloadditions of 156 and 157 with TCNE were rationalized as stepwise reactions involving the dipolar ions 158 (Scheme 23) [37],... 

The only successful [2 + 2] cycloaddition reported so far involving an MCP derivative and a carbon-heteroatom double bond is the reaction of BCP (3) with chlorosulfonylisocyanate (CSI) (594) [13b, 143], CSI is a typical [2 + 2] cycloaddend with most alkenes, but has been demonstrated to be also involved in stepwise cycloadditions via polar intermediates [157], The reaction of BCP and CSI gives the [2 + 2] cycloadduct 596 only as a minor product, besides the major [3 + 2] adduct 599 (Scheme 83) [13b, 143], Therefore, it has been reasonably suggested that both products derive from a common dipolar intermediate 595, formed by nucleophilic attack of BCP on the electron-deficient carbon of CSI (Scheme 83) [13b]. 

Olefinic, acetylenic, and typical electron-deficient dienophiles participate in apparent concerted [4 + 2] cycloadditions with the thioacylketene thioacetals (Scheme 8-V), while enamines provide modest yields of [4 + 2] cycloadducts via a polar, stepwise addition-cyclization.22c... 

A net [4+2] cycloaddition of benzyne to vinyl isocyanates allows one to construct phenanthridinones and benzphenanthradinones in one step and 40-50% yield . Thus lead tetraacetate oxidation of aminobenztriazole 66 in the presence of429 gave 430 in good yield. Whether the mechanism involves a concerted [4+2] addition to the 2-azadiene moiety of the isocyanate or a polar stepwise addition remains for further study. 

As a rule, cycloaddition is only partially stereoselective, though examples are cited in which stereoselectivity, which decreases with solvent polarity, is essentially complete. However, as Bartlett has pointed out [23] In general, configuration loss appears to be a sufficient but not a necessary criterion for stepwise cycloaddition, at least when the intermediate is a dipolar ion . 

Allenylidenecomplexes 46 also react with thecarbon-carbon triple bond ofynamines to yield similar mononuclear cydobutenyhdene derivatives 48, although mixtures with the corresponding alkenyl-aminoallenylidene spedes 49 are formed (Scheme 2.20) [ 1 Oc]. The former isomer results from the addition of the C=C bond of y namines across the Co,=Cp unsaturation, while the latter is provided bythe formal [2 + 2] cycloaddition between C=C and Cp=Cy bonds and subsequent cycloreversion. In both processes, stepwise cyclization initiated by the addition of the nucleophilic R C=CNEt2 carbon at the Co, or Cy position, respectively, is proposed. Relative proportions of 49 with respect to 48 increase with the electron-releasing capacity of the para-substituents of the diarylallenylidene skeleton (NMe2 > OMe > Me > H). In contrast, the formation of 48 is favored when the reaction is carried out in low polarity solvents. 

An important point, however, is that although the configurations of the reactants are preserved in the products (i.e. the additions are stereoselective), some cycloadditions, including those of ketenes to imines, occur more rapidly in polar rather than in non-polar solvents (Scheme 8.9). For such examples it may well be that the addition proceeds in a stepwise manner (non-concerted), and the collapse of a dipolar intermediate is so quick that the stereochemistry of the reacting species is not compromised. 

Amino-l,2,4-thiadiazoles 191 are obtained when ether is used (249), while 5-alkylthio-1,2,3-triazoles 192 result when the reaction is carried out in THF (250). Reaction of 3 with carbon disulfide leads to 5-alkylthio-l,2,3-thiadiazoles 193 (251). While 3 can act as a synthetic equivalent of the RC—N—N synthon (R = H, SiMea) in all these reactions, it should be emphasized that it does not react by a concerted 1,3-dipolar cycloaddition but rather by a stepwise polar mechanism. The highly nucleophilic character of 3 can account for why diazomethane and... 

Intramolecular ionic Diels-Alder reactions were carried out in highly polar media to afford carbocyclic ring systems. The strategy, which obviates the need for high temperatures and pressures, features in situ generation of heteroatom-stabUized allyl cations that undergo subsequent (4 + 2) cycloaddition at ambient temperature. Typically, reactions were complete within 1 hour after addition of substrate. Some cycloadducts were the result of a concerted process, whereas others were formed via a stepwise reaction mechanism (Grieco, 1996). 

The rates of Diels-Alder reactions are little affected by the polarity of the solvent. If a zwitterionic intermediate were involved, the intermediate would be more polar than either of the starting materials, and polar solvents would solvate it more thoroughly. Typically, a large change of solvent dipole moment, from 2.3 to 39, causes an increase in rate by a factor of only 10. In contrast, stepwise ionic cycloadditions take place with increases in rate of several orders of magnitude in polar solvents. This single piece of evidence rules out stepwise ionic pathways for most Diels-Alder reactions, and the only stepwise mechanism left is that involving a diradical. 

The controversy about the timing of bond formation in cycloadditions continues. Although stepwise reactions involving zwitterionic intermediates can be detected more or less reliably by solvent polarity effects on rates, the distinction between mechanisms involving diradical intermediates or no intermediates at all (concerted pathways) is a more subtle one. Whereas the articles of debate were formerly experimental data, the discussion has now expanded into the theoretical realm. 

In fact, the cycloaddition of butadiene to ethylene, as well as cycloadditions of similar non-polar dienes to non-polar alkenes seem experimentally to be cases where concerted and stepwise (biradical or biradicaloid) mechanisms compete. We have recently discussed a number of cases, such as the dimerization of butadiene, piperylene, and chloroprene, the cycloadditions of butadiene or methylated dienes to halogenated alkenes, and others, where non-stereospecificity and competitive formation of [2 + 2] adducts indicate that mechanisms involving diradical intermediates compete with concerted mechanisms10). Alternatively, one could claim, with Firestone, that these reactions, both [4 + 2] and [2 + 2], involve diradical intermediates1 In our opinion, it is possible to believe that a concerted component can coexist with the diradical one , and that both mechanisms can occur in the very same vessel 1 ). Bartlett s experiments on diene-haloalkene cycloadditions have also been interpreted in this way12). 

Similarly, from rix- and trans-1 -isobutenylidene-2-methyl-3-phenylcyclopropane and 4-phenyl-3//-1.2,4-triazole-3,5(4//)-dione, a mixture of regioisomeric monoadducts 16 and 17 with Z configuration is obtained and further isomerized to the (E)-isomers. The substrate-induced diastereo-selectivity in the cycloaddition of a second triazoledione molecule to the four isomers is dependent on the C-7 alkylidene group. The (Z)- and ( )-ethylidene and the (Z)-benzylidene derivatives undergo anti cycloaddition (from the side opposite the ring substituent at C-8), whereas the (Z)-benzylidene derivatives, for which a planar structure of the diene is not possible, affords the bisadduct formally derived by syn cycloaddition, most likely through a stepwise polar mechanism as observed in cycloaddition to (Z,Z) acyclic 1,3-dienes (Section 7.2.10.3.10.1.). 

Both concerted and stepwise mechanisms have been proposed for these reactions although the experimental facts can be readily accounted for by the formation of a 1,4-dipolar intermediate (27 Scheme 27). The reaction rates are markedly increased in polar solvents. The cycloadditions of isocyanates to alkenes are always regiospecific, the reaction taking place so as to form the most stable 1,4-dipole. 

These aspects introduce different mechanistic patterns expected for the 1,3-DC reactions, as compared with DA cycloadditions (concerted vs stepwise with some zwitterionic character). This result may again be traced to the electrophilicity difference at the ground states of the reacting pairs.39 These results suggest that the description of the reactivity and the reaction mechanism involved in the 1,3-DC processes can be systematized as in the case of the DA cycloadditions. Such a model should be able to determine the charge transfer pattern and to decide which of the partners is acting as nucleophile/electrophile in a polar process, or even to anticipate a concerted pathway in those cases where the electrophilicity/nucleophilicity difference is small. 

The past classification of the [4 + 2] cycloaddition reactions involving die 4it participation of a cationic heterodiene among the polar cycloadditions is derived not from an implied stepwise addition-cy-clization reaction mechanism but was terminology introduced to distinguish cycloadditions employing cationic or anionic components from those employing dipolar or uncharged components. Herein the reactions are simply referred to as [4 + 2] cycloaddition reactions. 

In many instances, the entropic assistance provided in the intramolecular Diels-Alder reaction is sufficient to promote azadiene participation in Diels-Alder reactions.12 The incorporation of the azadiene system, or dienophile, into a reactive or sensitive system, e.g., heterocumulene or strained olefin, allows a number of specialized azadiene Diels-Alder reactions. Many such examples may represent stepwise, polar [4 + 2] cycloaddition reactions. 

In the instances studied,65 67 the effect of solvent polarity on the rate of [4 + 2] cycloaddition is consistent with the reactions proceeding by stepwise, addition-cyclization reactions. 

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