Cycloadditions Involving Ketenes

2 Cycloadditions Involving Ketenes We next present two examples of cycloadditions involving ketenes that invoke a bifurcating PES. The cycloaddition of ketene with cy clopentadiene had long been thought to simply give the formal [2-1-2] product, such as the reaction of cyclopentadiene 67 with dichloroketene 68 

Singleton took up this problem, using a combined experimental/ computational/MD design. Careful monitoring of product formation at -20 °C showed that 73 was formed at early times even when the concentration of 72 was quite small. A kinetic model suggested that the rate constant for the formation of 73 (9.0 X 10 M s ) is only four times less than that for the formation of 72 (4.1 X 10 s ), while the rate constant for conversion of 72 into 73 is 2.9 X 

10 M i s-i.This is inconsistent with the proposed mechanism of Reaction 8.8. 

The KIE for 73 is negligible at C, (the cyclopentadienyl carbon that joins with the carbonyl carbon), suggesting that this bond must be fully formed before the rate-limiting step. However, there is a substantial isotope effect at Cj for 69, implicating that bond making is occurring at this center in the rate-limiting step. 

Direct dynamics trajectories were computed for both Reactions 8.7 and 8.8 using naPWlK/6-31G and mPWlK/6-31-l-G(d,p). Trajectories were initiated at 77 for Reaction 8.7 and at 74 for Reaction 8.8. Trajectories were run until a product was reached, a recrossing back to reactant occurred, or the elapsed time reached 500 fs. These trajectory outcomes are listed in Table 8.4. 

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Cycloadditions involving ketene derivatives as one or both reaction partners are assumed to be rare examples of concerted [7r2 + jt2] cycloadditions146. The activation volumes determined for the [2 + 2] cyclodimerization and the [2 + 2] cycloadditions... 

Frontier Orbital Interactions in the Transition State of One-Step [2+2]-Cycloadditions Involving Ketenes... 

Cycloadditions involving ketene derivatives as one or both reaction partners are assumed to be rare examples of concerted [tTj - - n cycloadditions [81]. The activation volumes determined for the [2 + 2] cyclodimerization of diphenylketene [82] and the [2 + 2] cycloadditions of diphenylketene to various enolethers [83] gave values of —30 cm mol and —22 to -52 cm mol , respectively, and were highly negative. Thus, the effect of pressure leads to a powerful acceleration of these [2 + 2] cycloadditions comparable to that with Diels-Alder reactions, a characteristic which is usefiil for synthetic purposes. For example, various /1-lactams can be easily synthesized by pressure-induced [2 + 2] cycloaddition of alkyl and aryl isocyanates and enolethers [84]. 

Ketenes are another type of unsaturated molecules of high electron deficiency and structural strains therefore, they are very reactive for the [2+2] cycloaddition. The most common [2+2] cycloaddition involving ketenes are Staudinger [2+2] Cycloadditions to form fi-lactones, initially reported in 1911, and the dimerization of ketenes." Besides the easy cycloaddition with imine, as shown in the Staudinger [2+2] Cycloaddition, ketenes can also react with aldehydes to afford /3-lactones. It has been found that high diastereoselectivity can... 

Cycloaddition involving ketene intermediates continue to provide a useful entry to cyclobutanones, and Snider et al. have given fuller details of the potential for Lewis acid-catalysed thermal [2 + 2]-cycloadditions involving acetylenes in the synthesis of cyclobutenes. 

Developments in the field of stereoselective 1,3-dipolar cycloadditions and their synthetic applications are outlined in Sections 18.2 to 18.4 [22, 23, 28-34]. Subsequently, related [2-i-3]-cycloadditions with 1,3-diradicals and trimethylenemethane equivalents that furnish the corresponding five-membered carbocycles are covered (Section 18.5) [38—41]. The chapter closes with a collection of [2-i-2]-cycloadditions involving ketenes (Section 18.6) [19, 35, 36], photochemical olefin cycloadditions, and Paterno-Biichi reactions (Section 18.7) [36, 37],... 

Cycloadditions give rise to four-membered rings. Thermal concerted [2+2] cycloadditions have to be antarafacial on one component and the geometrical and orbital constraints thus imposed ensure that this process is encountered only in special circumstances. Most thermal [2+2] cycloadditions of alkenes take place by a stepwise pathway involving diradical or zwitterionic intermediates [la]. Considerably fewer studies have been performed regarding the application of microwave irradiation in [2+2] cydoadditions than for other kinds of cydoaddition (vide supra). Such reactions have been commonly used to obtain /1-lactam derivatives by cycloaddition of ketenes with imines [18-20,117,118],... 

An important extension of the ketene acetal cycloaddition involved the diazoniapentaphenes. An example is the conversion of 4a,8a-bis(azonia)pentaphene (31) to a mixture of two diadducts of which 32 represents the stereoisomer formed by addition of both mole-... 

So special reactions are often used to make cyclobutanes. In the next chapter we shall see that thermal cycloadditions of alkenes with ketenes give four-membered rings, but the commonest method is photochemical cycloaddition. You are already aware that Diels-Alder reactions (chapter 17) occur easily when a diene 6 and a dienophile 7 are heated together and six-membered rings 8 are formed. Have you ever wondered why four-membered rings 9 are not formed instead Orbital symmetry allows cycloadditions involving six Ti-electrons but not those involving four 7r-electrons.2... 

The first example of a bimolecular 1,3-dipolar cycloaddition between an isomtinchnone and an electron-rich dipolarophile was reported by our group several years ago [27]. The reaction of diethyl ketene acetal and isomtinchnone 9 gave cycloadduct 29 in high yield. Again, only one regioisomer was obtained and the regiochemistry encountered is consistent with cycloaddition involving the HOMO of diethyl ketene acetal and the LUMO of isomunchnone 12 (n = 1). 

The Reformatsky reactions of methyl or ethyl bromoacetate with 4-acetoxy-,2,24 4-benzyloxy-,2 4-tetrahydropyranyloxy-,2 4-chloro-,8 and 4,4-dimethoxy-2-butanone1418 have been carried out. The adducts were converted to mevalonolactone by hydrolysis and, in the case of the acetal reactant, by appropriate reduction and oxidation procedures. The same Reformatsky-type syntheses of mevalonolactone have also been performed using the lithium and magnesium carbanions of acetate esters5,19 25 26 and the dianion of acetic acid28,27 instead of the usual zinc reagent. The intramolecular Reformatsky reaction of 4-(bromoacetoxy)-2-butanone gives mevalonolactone directly.28 A related route to mevalonolactone involves boron trifluoride-catalyzed cycloaddition of ketene to 4-acetoxy-2-butanone followed by hydrolysis.183... 

There is ample evidence that these cycloadditions involve the initial formation of a dipolar intermediate (5 Scheme 6). Conrotatory cyclization of (5) leads to the 3-lactam. Intermediates of type (5) can be trapped by another molecule of ketene to yield (d) or by sulfur dioxide to yield sulfone (7). This mechanism also explains the formation of [4 -I- 2] adducts (8) which are sometimes observed with conjugated imines. ... 

To summarize, most [2 + 2] cycloadditions are light-promoted. The only concerted thermal [2 + 2] cycloadditions involve a ketene or other cumulene, or a compound in which a heavy atom such as P or a metal is doubly bound to another element. 

Although no preparatively useful metal-catalyzed [3-F 2]-cycloaddition reactions involving ketenes have been developed due to the pronounced [2-F2]-cycloaddition reactivity of this substrate vide supra), ketene derivatives, e.g. ketenimines, are much less prone to undergo [2 + 2] cycloadditions, so that [3-1-2] cycloaddition can successfully compete. However, instead of the primarily expected 2,4-bis(methylene)pyrrolidines or a-methylene-d -pyrrolines, substituted pyrroles are formed whenever double-hond isomerization is possible. For example, such a reaction smoothly proceeds with the parent MCP (4) and iV-phenyldiphenylketenimine (19) which provides 2-(diphenylmethyl)-4-methyl-l-phenylpyrrole (20) in 96% yield. 

More recently, results have been published indicating that the initial condensation, at least in the presence of triethylamine, may not be only of the aldol type but also include a pathway involving the formation and subsequent cycloaddition of ketene to form a 3-lactone intermediate that cleaves to provide... 

The 1,4-cycloaddition of ketenes to A, A -disubstituted enaminones allows a general synthesis of pyranones. Berchtold and co-workers (61JOC4776 65JOC2642) showed that treatment of ethyl 3-pyrrolidinocrotonate 341 (R = EtO) or 4-pyrrolidino-3-penten-2-one 341 (R = Me) with an excess of ketene resulted in the formation of pyranones 342, Scheme 96. The mode of formation of 342 apparently involves initial acetylation with one mole of ketene at the enaminone fi position followed by cycloaddition with a second mole of ketene. 

Other cycloadditions. A [3+2]-cycloaddition involving a benzoquinone and an alkene to give 2,3-dihydrobenzofuran derivatives, and an intramolecular [4+3]-cycloaddition to provide functionalized polycyclic compounds, are further demonstrations of the utility of LiClQj-OEtj. The reaction of aromatic or a,p-unsaturated aldehydes with acid chlorides proceeds via ketenes and then 2-oxetanones. ... 

The 2-benzylindole-3-carboxylic ester (372) is postulated to form the carbanion on treatment with base, and the product of its addition to DMAD is the hydroxycarbazole (373) (Equation (106)) <92TL1655>. It is possible that the reaction is actually a cycloaddition involving a quinodimethane ketene structure (see Section 2.02.1.8). 

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