Zwitterion trapping

Hydrogen atoms in azolium ions can be removed easily as protons (e.g. 230—>232) exchange with deuterium occurs in heavy water. The intermediate zwitterion (e.g. 231) can also be written as a carbene, and in some cases this carbenoid form can be trapped or isolated as a dimer. 

A strong acceptor TCNE undergoes [2+2] rather than [4+2] cycloaddition reactions even with dienes. 1,1-Diphenylbutadiene [20] and 2,5-dimethyl-2,4-hexadiene (Scheme 5) [21] afford mainly and exclusively vinyl cyclobutane derivatives, respectively. In the reactions of 2,5-dimethyl-2,4-hexadiene (1) the observed rate constant, is greater for chloroform solvent than for a more polar solvent, acetonitrile (2) the trapping of a zwitterion intermediate by either methanol or p-toluenethiol was unsuccessful (3) radical initiators such as benzyl peroxide, or radical inhibitors like hydroquinone, have no effect on the rate (4) the entropies of activation are of... 

The suggested fragments from (54a) are a carbonyl compound (58) and a peroxy zwitterion (59), the latter then effecting a 1,3-dipolar addition on the former to yield the ozonide (57a). Alternative reactions of the zwitterion (59), including its polymerisation, lead to the formation of the abnormal products that are sometimes observed in addition to the ozonide, If ozonolysis is carried out in MeOH as solvent then (59) is trapped , as it is formed, by its conversion into the relatively stable a-hydroperoxy ether (60) ... 

In acetic acid the intermediate zwitterion is trapped by acetate affording cyclopentenones with an acylated hydroxymethylene group on C-4. Use of this sequence has been made of in the synthesis of the sesquiterpenes cyclocolorenone 347) (3.31) and a-cadinol (3.32) 348). 

Electrocyclization of 1,4-dienes is an efficient process when a heteroatom with a lone pair of electrons is placed in the 3-position, as in 77 (Scheme 20)38. Photoexcitation of these systems generally results in efficient formation of a C—C bond via 6e conrotatory cyclization to afford the ylide 78. These reactive intermediates can undergo a variety of processes, including H-transfer (via a suprafacial 1,4-H transfer) to 79 or oxidation to 80. In a spectacular example of reaction, and the potential it holds for complex molecule synthesis, Dittami and coworkers found that the zwitterion formed by photolysis of divinyl ether 81 could be efficiently trapped in an intramolecular [3 + 2] cycloaddition by the... 

Analogous olefin trapping chemistry employing 2,7-cyclooctadienone has been investigated51. With this substrate, the oxyallyl zwitterion 112 could be intercepted intermolecularly with simple alkenes in a (presumably stepwise) 3 + 2 manner (Scheme 27). Importantly, intermediate 112 differs from 2,5-cyclohexadienone-derived zwitterions in terms of its lack of a facile rearrangement pathway. An interesting side-issue... 

As noted above, formation of a furan [4 + 3]-cycloadduct during irradiation of a 4-pyrone was advanced as evidence for the zwitterionic intermediate. This process can be moderately efficient (equation 4)68, and can be envisioned as an approach to substituted cyclooctanoids. Besides the formation of three new carbon-carbon bonds, an additional attractive feature is the complete diastereoselectivity, arising from a compact [4 + 3]-cycloaddition transition state with approach from the face opposite the epoxide. However, the generality of the intermolecular reaction is limited, as competing [2 + 21-photodimerization, solvent trapping and rearrangement often predominate58. 

Attempts to liberate l-methyl-l-aza-2,3-cyclohexadiene (329) from 3-bromo-l-methyl-l,2,5,6-tetrahydropyridine (326) by KOtBu in the presence of [18]crown-6 and furan or styrene did not lead to products that could have been ascribed to the intermediacy of 329 (Scheme 6.70) [156], Even if there is no doubt as to the allene nature of 329 on the basis of the calculations on the isopyridine 179 and 3d2-lH-quinoline (257), it is conceivable that the zwitterion 329-Za is only a few kcal mol-1 less stable than 329. This relationship could foster the reactivity of 329 towards the tert-butoxide ion to an extent that cycloadditions to activated alkenes would be too slow to compete. On the other hand, the ultimate product of the trapping of 329 by KOtBu could have been an N,0-acetal or a vinylogous N,0-acetal, which might not have survived the workup (see, for example, the sensitivity of the N,0-acetal 262 [14], Scheme 6.57). 

Desulphurization of compounds such as (58) has again attracted attention.69 In the case of (58), complete desulphurization gives (60), and the reaction was shown by trapping experiments to occur via the zwitterion (59). 

The formation of anthracene in reactions of 185 and 186 with benzyne, which was unexplained by Wittig et aZ., possibly is due to an alternative reaction of the intermediate zwitterion (202) with another molecule of benzjme or with a benzyne precursor. Benzyne reacted with the isoindole (206) to give the tetramethyltriptycene (208) and, in a separate run using excess of the benzyne precursor, W-benzylcarbazole. The latter product would appear to be made up of the iV-benzyl group from an intermediate anthracen-9,10-imine (207) and two molecules of benzyne. Mass spectral evidence also implicated the adduct 207, and the formation of 208 was attributed to benzyne-induced deamination of 207 to 1,4,9,10-tetramethylanthracene, which was trapped by further addition of benzyne across the 9- and 10-positions. 

Padwa has shown that rhodium-catalyzed oxidation of indolyl carbamate 67 employing either Phl(OAc)2 or Phl=0 follows a path similar to that of the D-aUal carbamate (Scheme 17.26) [95]. In principle, indole attack of the putative rhodium-nitrene generates zwitterion 68, which is trapped subsequently by an exogenous nucleophile. Spiro-oxazolidinone products (for example, 69) are isolated as single diastereomers in yields ranging from 50 to 85%. As an intriguing aside, Padwa has found that certain carbamates react with Phl=0 in the absence of any metal catalyst to furnish oxazoHdinone products. This result may have implications for the mechanism of the rhodium-catalyzed process, although it should be noted that control experiments by Espino and Du Bois confirm the essential role of the metal catalyst for C-H amination [57]. 

Ozonolysis of alkenes in participating solvents such as alcohols often leads to trapping of intermediates. Most commonly, an alcohol will react with the carbonyl oxide zwitterion, generated from cycloreversion of the primary ozonide (Section 4.16.8.2), to give an alkoxy hydroperoxide. The secondary ozonide (1,2,4-trioxolane) is usually more stable to nucleophilic attack from alcohols. 

A 2-Methylpyridine can be deprotonated by a base such as sodium methoxide and the resultant anion can be reacted with ben-zaldehyde to form a hydroxylated adduct (Scheme 2.21). This product can then be dehydrated by acid, or base, to form the conjugated compound stilbazole. Alternatively 2-methylpyridine can be A -acetylated by reaction with acetic anhydride and the initial product deprotonated to give an A -acetylenamine intermediate that traps benzaldehyde, A similar reaction to that of the first procedure occurs, but under the reaction conditions the zwitterionic (dipolar) product eventually loses acetic acid, perhaps by an interna shift of an acetyl group from nitrogen to oxygen. 

Yokozawa reported that the 2-substituent strongly affects the reactivity of a 2-substituted-oxazoline 360 with dimethyl 2,2-dicyano-3-ethoxy-l,l-dicarboxylate as shown in Scheme 8.115. Thus, oxazoline itself, 360 (R = H), gave the annulated bicyclic product 361 that resulted from collapse of the zwitterionic intermediate 362, whereas simple 2-alkyloxazolines, 360 (R = Me, Et), gave an alternating (1 1) copolymer. 2-Phenyloxazoline, 360 (R = Ph), was unreactive under the reaction conditions. The zwitterionic intermediate 362 (R = Me) was trapped by acetic acid to give the open-chain adduct 363 that resulted from nucleophilic ring opening at the 5-position of the oxazolinium zwitterion. 

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