Mechanism of 2 + 2,-cycloadditions

Scheme 5.7 Proposed mechanism of [3+2] cycloaddition reaction of internal alkynes...

Eq. 17 is meant to represent the possibility for a concerted formation of oxetane product. A problem that always exist in cycloadditions is the question of whether the reaction takes place by a two-step biradical reaction pathway or through a concerted mechanism. Such questions have not even been resolved for purely thermal reactions. 4> A recent speculation on this point proposes almost universal concertedness for all cycloaddition reactions. 79> In that work, mixed stereochemistry in the products of [2+2] cycloaddition reactions is generally attributed to a mixture of two concerted reactions, suprafacial-suprafacial, and supra-facial-antarafacial. It will be seen later that the PMO calculations generally do not support this idea. A mixture of biradical and concerted reactions is in better agreement with experimental facts. 

Determination of the Configurations and Study of Stereodynamics of Cyclic Nitroso Acetals This determination is of obvious fundamental importance by itself and, in addition, it is of importance in considering the mechanism of [3+ 2]-cycloaddition and in predicting the conhgurations of the resulting stereocenters. 

The mechanism again consists of a series of [2 + 2] cycloadditions and retrocycloadditions. 

Thermal cleavage of cyclobutanes961 to give two olefin molecules (cycloreversion,962 the reverse of 2 + 2 cycloaddition) operates by the diradical mechanism, and the [ 2S +, 2a] pathway has not been found963 (the subscripts a indicate that a bonds are involved in this reaction). 

The initially formed bicyclic compound 38 has a highly strained and very reactive bridgehead endocyclic Si—Si bond. It can easily react with a second molecule of benzaldehyde by the insertion pathway to form a new bicyclic compound 40 with a norbornane type skeleton (Scheme 14 and Figure 12). Although this last reaction closely resembles the previous case of phenylacetylene22, the mechanism is evidently different in the case of phenylacetylene the final product 36 is a result of [2 + 2] cycloaddition of the second molecule of phenylacetylene across the new Si=Ge double bond, whereas in the case of benzaldehyde the final norbornane 40 is a result of the insertion of the second molecule of benzaldehyde into the strained Si—Si single bond. Apparently, the reactions of disi-lagermirenes with phenylacetylene and benzaldehyde have the same initial steps to form bicyclic compounds, but then the reaction pathways become different due to the different nature of these intermediate bicyclic compounds. 

This process, formally related to the Diels Alder reaction, may also proceed by various mechanisms (Scheme 6.257)1421 1443 similar to those of [2 + 2] cycloaddition (Scheme 6.251), such as a concerted process or formation of charge-transfer (exciplex, 532), biradical (533), zwitterion (534) or perepoxide (535) intermediates. A concerted pathway1444 and exciplex1445 intermediacy was proposed to be involved in most cases. The [4 + 2] photooxygenation may be accompanied by other related processes (e.g. [2 + 2]). 

Low-valent transition metal catalyzed versions of [2 + 2] cycloadditions. especially with nickel catalysts, were recognized early as useful alternatives to thermal and photochemical methods12-15. The observation of transition metal catalysis, active in [2 + 2]-cycloaddition reactions, originally caused considerable discussion of the mechanism as an inversion of symmetry rules, effected by the transition metal, may be assumed. Thus, it was suggested that, in the presence of the metal catalyst, a forbidden reaction becomes allowed 16,17. This interpretation, however, could not be verified for the overall process, since experimental investigations revealed a stepwise mechanism with metallacycle intermediates18-23. 

More recent views on the theory of (2 + 2)-cycloaddition, in particular with respect to the question whether the two novel o-bonds are formed via a concerted or a stepwise mechanism, have been presented by Epiotis.28 He predicts that, if in the reaction of two n -electron systems one of the reactants has an electron-donating and the other an electron-accepting character, the activation energy of the concerted non-allowed 1 2 + n2s]-cycloaddition will be lowered, so that such a reaction may occur in a concerted manner under relatively mild conditions. As this condition is satisfied in most of the reported thermal (2 + 2)-cyclo-addition reactions of heterocyclic compounds, care must be taken in drawing any conclusions as regards the reaction pathways followed. 

Four different types of (2 + 2)-cycloaddition and -cycloreversion reactions of heterocyclic compounds are known intermolecular and intramolecular reactions, both thermal and photochemical. Three of these have already been discussed in the previous sections on (2 + 2)-cycloadditions, and as far as the mechanism is concerned both the forward and the reverse reaction suffer from the same ambiguity Do they proceed via a concerted or a nonconcerted mechanism do they involve an ionic or a diradical intermediate are they symmetry-allowed or forbidden So far only one reaction type is known to be limited to the reverse reaction, viz., the thermal intramolecular reaction [Eq. (10)], in which one o-bond is broken and a conjugated -electron system is... 

Assuming the mechanism of 1,2-cycloaddition is similar to 1,4-cycloaddition (i.e., the Diels-Alder reaction), is the product obtained from the addition of cyclopentadiene and ketene the expected one Explain. 

Bearing in mind the stereospecificity of [2 + 2] cycloaddition, a concerted mechanism of the reaction has been proposed [91-94]. This proposition has been further partially supported by the ah initio calculations performed by Ugalde et al. [95,96]. They concluded that in the gas phase and in some cases in solution the mechanism is concerted. 

In Section 24.12, we introduced alkene (olefin) metathesis, i.e. metal-catalysed reactions in which C=C bonds are redistributed. The importance of alkene and alkyne metathesis was recognized by the award of the 2005 Nobel Prize in Chemistry to Yves Chauvin, Robert H. Grubbs and Richard R. Schrock for the development of the metathesis method in organic synthesis . Examples of alkene metathesis are shown in Figure 27.3. The Chauvin mechanism for metal-catalysed alkene metathesis involves a metal alkyli-dene species and a series of [2 + 2]-cycloadditions and cycloreversions (Figure 27.4). Scheme 27.6 shows the mechanism for alkyne metathesis which involves a high oxidation state metal alkylidyne complex, L M=CR. 

The discussion in this chapter has ranged well outside the main theme of the book. In addition to the writer s early involvement with secondary isotope effects, which can serve as partial extenuation, the mechanism of [2-f2]-cycloaddition has sufficient intrinsic interest to justify the digression. Orbital symmetry conservation plays but a small part in its mechanistic analysis, but it is a crucial one. Fig. 6.2 applies strictly only to the cyclodimerization of ethylene, or to an olefin symmetrically tetrasubstituted by substituents that do not add to the essential number of electrons involved in the reaction. Nevertheless, the principal conclusion drawn from it, that the initial plane-rectangular interaction of the two tt systems leads to formation of a bond between diagonally situated atoms, is remarkably robust. It can be applied to a variety of reactions with different electronic and steric requirements, provided that the specifics of each reacting system are kept firmly in mind. The wealth of diverse, superficially contradictory, experimental results cannot be fit into a consistent logical framework without it. 

The slow initiation step can be rationalized by a mechanism involving [2+2] cycloaddition of the olefin at the Ru=C bond of the vinylidene ligand, with generation of a new Ru carbene species able to propagate faster polymerization (Scheme 14). This mechanism has been documented by Ozawa" for ROMP of norbomene with [RuCl2(PPh3)2(=C=CHFc)] (Fc = ferrocenyl) and by Kirchner in a stoichiometric reaction using a Tp-coordi-nated Ru complex (Tp = tris(pyrazolyl)borohydride)." ... 

The first catalytic asymmetric version of [2 + 2] cycloaddition reaction was realized by Narasaka in 1989 using chiral titanium catalyst derived from TADDOL. It was found that the reaction of ketene dithioacetal with acryloyloxazolidinone derivatives proceeded smoothly in the presence of 10 mol% of TADDOL-TiCl2 to give the cyclobutane derivatives in high yields (64-96%) and good to excellent enantioselectivities (80-98%) [183]. The reaction is presumed to proceed via a carbonyl substrate chelated TADDOL-TiCb intermediate although the exact reaction mechanism is unclear. Moreover, alkynyl, alkenyl, and 1,2-propadienyl... 

A molecular-orbital and density-functional theory study has been reported for the mechanism of 2- -1-cycloaddition of hydrogen isocyanide to alkenes. The... 

The reaction mechanism of [5+2]-cycloaddition is likely to proceed through the following steps initially, the cyclopropylenyne reacts with the Ru-complex to form the ruthenacyclopentene 188 through the intermediate complex 187, then ensues the C-C cleavage of the cyclopropane ring to give the ruthenacyclooctadiene 189. Finally reductive elimination affords the product 180 (Scheme 81). 

Unless they have considerable strain in their ring systems, cyclophanes can be formed by most conventional bond-forming reactions. The first photochemical approach was applied by Schonberg et al. to prepare cage compound 1, a cyclophane, in 1968. Moreover, styrene photocyclodimerization (Scheme 1) was also published in the same year, > although it took almost two decades before we first successfully applied the reaction to cyclophane synthesis." The mechanism (Scheme 1) of [2 + 2] cycloaddition with direct photoirradiation of vinylarenes and their derivatives has been published."... 

Lately a third type of transition state has been favored for [2 + 2] cycloadditions forming carbocyclic and heterocyclic four-membered rings. The experimental data on the addition of diarylketenes to arylethylenes are well accommodated by the [ 2s + 2s + 2s] process proposed by Baldwin (70JA4874). The steric effects on the cycloaddition of allenes to ketenes also favor this mechanism (76JA7698). 

Two extreme mechanisms can be envisaged (Scheme 12), concerted [2 + 2] cycloaddition or the more generally accepted formation of a dipolar intermediate (164) which closes to a /3-lactam or which can interact with a second molecule of ketene to give 2 1 adducts (165) and (166) which are sometimes found as side products. In some cases 2 1 adducts result from reaction of the imine with ketene dimer. 

On the other hand, the known facts point to an alternative interpretation. The stereochemical course of the reaction may be explained in terms of a polar [2s + 2s] cycloaddition15 which is observed in reactions between very electron-poor and very electron-rich alkcnes. Namely, polar [2 + 2] cycloadditions usually proceed with high regioselectivity ( head to head ) and stereoselectivity under mild conditions33 35. This mechanism is also supported by the fact that a closely related reaction (between an ynamine and iminium salts) passes through a cyclic 4-membered intermediate36, which is probably the result of a polar [2 + 2] cycloaddition (see refs 10 and 37). 

It must be emphasized once again that the rules apply only to cycloaddition reactions that take place by cyclic mechanisms, that is, where two s bonds are formed (or broken) at about the same time. The rule does not apply to cases where one bond is clearly formed (or broken) before the other. It must further be emphasized that the fact that the thermal Diels-Alder reaction (mechanism a) is allowed by the principle of conservation of orbital symmetry does not constitute proof that any given Diels-Alder reaction proceeds by this mechanism. The principle merely says the mechanism is allowed, not that it must go by this pathway. However, the principle does say that thermal 2 + 2 cycloadditions in which the molecules assume a face-to-face geometry cannot take place by a cyclic mechanism because their activation energies would be too high (however, see below). As we shall see (15-49), such reactions largely occur by two-step mechanisms. Similarly. 2 + 4 photochemical cycloadditions are also known, but the fact that they are not stereospecific indicates that they also take place by the two-step diradical mechanism (mechanism... 

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