Retro concerted

Oxazolium oxides, which can be generated by cyclization of a-amido acids, give pyrroles on reaction with acetylenic dipolarophiles.144 These reactions proceed by formation of oxazolium oxide intermediates. The bicyclic adduct can then undergo a concerted (retro 4 + 2) decarboxylation. 

The mode of reaction of titanacydobutenes with carbonyl compounds is largely dependent on steric factors (Scheme 14.31) [72]. Ketones and aldehydes tend to insert into the titanium—alkyl bond of 2,3-diphenyltitanacydobutene, and homoallylic alcohols 70 are obtained by hydrolysis of the adducts 71 [65a,73]. On the contrary, when dialkyl-substi-tuted titanacydobutenes are employed, the reaction with aldehydes preferentially proceeds through insertion into the titanium—vinyl bond. Thermal decomposition of the adducts 72 affords conjugated dienes 73 with E-stereoselectivity as a result of a concerted retro [4+2] cycloaddition [72]. 

The geometry of (c) makes conrotatory twisting of the two methylene groups (6 retro n6s + to2s) impossible. So if it has to be concerted, the elimination would have to be non-linear cheletropic. 

In the present chapter, however, because the problem is considered from a retrosynthetic point of view, we will distinguish only between heterolytic and homolytic disconnections -to which we will refer to as "retro-annulations"- and concerted or "pericyclic (or cheletropic) cycloreversions". In the same way that Woodward-Hoffmann rules [2] apply to pericyclic reactions, the Baldwin rules [3] may be said to apply to heterolytic as well as to homolytic "monotopic" annulations (see Table 6.1). Although in the preceding Chapter (see 5.5) we have already described some radical "monotopic" annulations, later on in this Chapter (see 6.1.3) and mainly in Chapter 7 we will refer to some new methods, syntheses and strategies which have been developed recently. 

The retro-Diels-Alder reaction has been reviewed.A fully concerted cyclic transition state has been proposed for conrotatory opening of cyclobutenes, in order to account for the low activation entropy and unexpected activation volume of ca —2 to —3cm mol . ... 

Azolines of type (13) undergo thermal decomposition in an analogous way to that already discussed for azolones (see Section 4.14.5.2) (Scheme 19). Path (i) is followed by those azolines having Z = S and path (ii) by those with Z = O. Path (i) is a typical retro-1,3-dipolar cycloaddition process, via an intermediate nitrile sulfide, while path (ii) might involve an acyl (Y = Z = O) or thioacyl (Y = S, Z = O) nitrene intermediate (136), which in turn rearranges to iso(thio)cyanate. However, no systematic attempts to trap this possible nitrene intermediate seem to have been made, and so a concerted pathway for the fragmantation cannot be ruled out. 

In Scheme 2.29b the nucleophile is indole (see Chapter 7), acting as an enamine. It seems likely that the size of the attacking reagent in this case is influential in directing addition solely to C-4. The reaction in Scheme 2.29c exemplifies nucleophilic addition followed by a concerted retro-cyclization process. 

Retro-Diels-Alder reactions have long been studied and discussed with an emphasis on whether they should be considered concerted or step-wise processes. Femtosecond real time studies of representative retro-Diels-Alder reactions of simple hydrocarbons have helped to provide an answer and to sharpen the nature... 

The dihydropyridazine (764) is unstable and loses nitrogen rapidly to yield a 1,3-diene (765) (69JA777, 72CC1260). Since (764) is generated by hydrolysis and oxidation of the cycloadduct (763) prepared from azodicarboxylate and2,4-hexadiene, it has proven possible to functionalize the double bond of (763) prior to nitrogen extrusion. Cyclopropanation, hydrolysis, decarboxylation and oxidation of (763) produce the 2,4-heptadiene (767) in a stereospecific manner via a concerted, orbital symmetry allowed retro-Diels-Alder process (Scheme 177). 

The first addition of a fully aromatic pyridine, as opposed to a 2-pyridone, across the 2,5-positions, which might be a concerted Diels-Alder reaction, takes place between the bis-dimethylaminopyridine (161) and DMAD at 110°. The product (163) was obtained in 67% yield and appears to be formed via 162, which undergoes a retro-Diels-... 

A review of direct observation of the transition state has traced the development of the femtosecond reaction dynamic technique, which has been used to demonstrate that the retro-Diels-Alder reaction can proceed by a stepwise mechanism as well as the usual concerted process.28 The oxide anion accelerated retro-Diels-Alder reaction has also been reviewed29 and the promise of this mild reaction for synthetic application has been emphasized. 

Ab initio molecular orbital calculations have been carried out by Ignacio and Schlegel on the thermal decomposition of disilane and the fluorinated disilanes Si2H F6 17. Both 1,1-elimination of H2 or HF and silylene extrusion by migration of H and F atoms concerted with Si—Si bond cleavage were considered. The transition states for the extrusion reactions all involved movement of the migrating atom toward the empty p-orbital of the extruded silylene in the insertion which is the retro-extrusion (equation 5). 

The deuterium KIE of 2.5 0.1, observed at 297 K in the cleavage of tributyltin allylsulphinate with [2H]TFA in toluene435 (equation 227) has been interpreted as suggesting a rigid compact and reactant-like early TS, and as confirming the concerted retro-ene mechanism of thermal desulphination of allylsulphinic acid (equation 228). The mechanism of hydroxyl radical-induced decarboxylation of 2-(alkylthio)ethanoic acid... 

Density functional theory studies of intramolecular retro-ene reactions of allyldiazenes have shown that the reaction is a concerted process involving a six-centre cyclic transition state.13 The cis- and tnms-allyldiazencs can interconvert by rotation around the double bond or by nitrogen inversion, it being predicted that nitrogen inversion is favoured. 

In the formation of tetraenes from bicyclo[4.2.0]octa-2,4-dienes, two bonds are broken. This may occur in one concerted reaction which can be regarded as a retro [2 + 2] cycloaddition. It is also possible that the central bond, being part of a cyclohexadiene system, is the first one to break in a thermal, concerted disrota-tory process that leads to a 1,3,5-cyclooctatriene derivative. Ring opening of the cyclooctatriene then might take place photochemically, again disrotatory, to produce a tetraene. This two-step sequence was first observed by Mirbach et al. [114] in their study of the photocycloaddition of the two parent molecules benzene and ethene. The same explanation for the formation of a tetraene was given by Nuss et al. [160] in their report on the intramolecular ortho photocycloaddition of ( )-6-(2-methoxyphenyl)-5,5-dimethyl-2-hexenenitrile (see Scheme 40). 

The continuing accumulation of experimental material made it, however, still more apparent that the above criteria, both kinetic and stereochemical [61-64], cannot be regarded as absolute [65], since there are probably both concerted reactions which are forbidden as well as nonconcerted ones which are allowed. An example of the first type of reaction is some 2 + 2 retro-cycloadditions on sterically strained systems [62,66] the second type of processes is then represented by the so-called multibond reactions [67]. This, of course, stimulates to formulate a new and more universal criterion of concertedness as well as a deeper understanding of the very concept of concertedness. 

The mechanism and kinetic aspects of the retro-ene reaction of the allyl n-propyl sulfide and its deuterated derivatives have been studied using four different types of DFT methods with eight different levels of the basis sets.7 The mechanistic studies revealed that the reaction proceeds through an asynchronous concerted mechanism. Theoretical calculations have indicated that the reaction displays a kinetic isotope effect of 2.86 at 550.65 K. 

Competitive experiments with 2H-, 13C- and 180-labelled chorismate derivatives and three different chorismate mutase enzymes have shown that in all catalysed and non-catalysed Claisen rearrangements a non-synchronous, concerted, pericyclic transition state is involved, with C-O bond cleavage considerably in advance of C-C bond formation. Some evidence has suggested that the ionic active site of the enzymes may polarize the transition state more than occurs in solution. Similar findings apply to the retro-ene fragmentation of chorismate to 4-hydroxybenzoate.17... 

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