Zwitterion intermediates rearrangements

The rearrangement (automerization) of Dewar thiophene 5-oxide (61), observed by NMR, occurs so much more rapidly than that of the corresponding episulfide that special mechanisms have been invoked. The one which involves a zwitterionic intermediate (Scheme 108) is favored over a pseudopericyclic sulfur-walk mechanism in which the electrons of the carbon-sulfur o--bond and the pair of electrons on sulfur exchange places as the sulfur atom migrates around the ring (80JA2861). 

Ketenes react with tertiary allylic amines in the presence of Lewis acids to give zwitterionic intermediates which undergo [3,3]-sigmatropic rearrangement [119]. Photolysis of chromium carbene complexes in the presence of tertiary amines results in similar chemistry [120]. Cyclic (Table 21) and strained allylic amines (Eq. 34) work best, while acylic amines are less reactive (Eq. 35). 

Zimmerman(24,a6> has provided strong circumstantial evidence that zwitterionic intermediates can be involved in formation of cyclopropyl ketones from dienones. His approach was to generate the dipolar species via ground state chemistry and show that these rearrange to the photoproduct ... 

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. 

The heterocycle decomposes readily, and the intermediate zwitterion alternatively rearranges to a vinylic ester that retains the phosphoryl isocyanate linkage. 

Nitrosobenzenes react with the carbonyl group of aldehydes to yield hydroxamic acids 73, according to reaction 20. Recently, the reactions between some X-substituted nitrosobenzenes (X = H, p-Me, p-C 1, m-Cl, p-Br) and formaldehyde were reported194 in order to investigate the mechanism of the hydroxamic acid formation. The mechanism reported in Scheme 9 involves a first equilibrium yielding the zwitterionic intermediate 74 which rearranges (by acid catalysis) into hydroxamic acid 75. The presence of a general acid catalysis, the substituent effect (p values of the Hammett equation equal —1.74),... 

In 1991 Fischer et al. observed the interesting phenomenon that treatment of benzyUdene tungsten carbene complex 9 with triphenylketeneimine at —70 °C in CH2CI2 gave zwitterionic intermediate 11, which was derived from the rearrangement of the initially formed zwitterioinic intermediate 10 [5]. Careful analysis of... 

In a special case, the spirocyclic oxazoline 640 was found to be unstable and undergoes rearrangement to the thietane A -acylimine 641 (Scheme 8.202). ° A zwitterionic intermediate 642 was proposed to account for the formation of 641. A biradical 643 is also a possible intermediate for this rearrangement. 

An alternative mechanistic interpretation of the methylenecyclobutane rearrangement is the postulation of a 2,2 -bisallyl (or 2,3-dimethylenebutane-l,4-diyl) diradical or zwitterionic intermediate.83... 

Although all the products can be rationalized on the basis of 7-hydrogen abstraction followed by cyclization or rearrangement-cyclization of 1,4-biradical intermediates, the mechanism has been shown to involve analogous zwitterionic intermediates [299b, 301], Although they are not strictly Norrish II reactions, transformations of 98 will be considered so for the purposes of discussion since the photoproducts and the mechanisms of their formation are very similar to those expected of Norrish II processes. 

If a diene unit is located at an appropriate distance from the developing zwitterionic intermediate in such reactions (especially in good ionizing solvents), an intramolecular cycloaddition may intervene. This is what happens with the tetrahydrobenzo[c]thiophene 2,2-dioxide derivative (588), which leads to the bis-homobenzene (589) rapid valence isomerization of this gives the product (590) (770R(25)i). This process has been termed bis-homoconjugative rearrangement (Scheme 251). 

The overall mechanistic picture of these reactions is poorly understood, and it is conceivable that more than one pathway may be involved. It is generally considered that cycloheptatrienes are generated from an initially formed norcaradiene, as shown in Scheme 30. Equilibration between the cycloheptatriene and norcaradiene is quite facile and under acidic conditions the cycloheptatriene may readily rearrange to give a substitution product, presumably via a norcaradiene intermediate (Schemes 32 and 34). When alkylated products are directly formed from the intermolecular reaction of carbenoids with benzenes (Scheme 33 and equation 36) a norcaradiene considered as an intermediate alternatively, a mechanism may be related to an electrophilic substitution may be involved leading to a zwitterionic intermediate. A similar intermediate has been proposed143 in the intramolecular reactions of carbenoids with benzenes, which result in substitution products (equations 37-40). It has been reported,144 however, that a considerable kinetic deuterium isotope effect was observed in some of these systems. Unless the electrophilic attack is reversible, this would indicate that a C—H insertion mechanism is involved in the rate-determining step. 

The rearrangement (Scheme 26) seems to be due to heterolysis of the C3a—C4 bond and rotation about the C7—Cla bond with subsequent formation of zwitterionic intermediate 51. 

Thus, ketenes (2) can react as dienophiles with (E)-l,3-diazabuta-l,3-dienes (E)-(25) to yield either [4 + 2] cycloaducts (26) or (27) depending on the participation of the C = C or C = O moieties of the ketenes (Scheme 7). Claisen rearrangement of 3,6-dihydro-2-methylene-2//-l,3,5-oxadiazines (27) yields the p-lactams (28). Alternatively, reaction between ketenes (2) and (Z)-l,3-diaza-buta-1,3-dienes (Z)-(25) leads to the usual zwitterionic intermediates (29), whose conrotatory electrocyclation leads to p-lactams (28). No computational data including solvent effects have been reported for these reactions. 

Isocyanides, formal divalent carbon functionalities, are ideal candidates for the development of MCRs. Their reaction with carbonyls and imines, through an a-addition process, generates a zwitterionic intermediate, which is then trapped by a nucleophile. The resulting double a-addition adduct is unstable and rapidly undergoes the Mumm rearrangement to afford the final product (Scheme 12.32). The venerable three-component Passerini reaction is the first MCR based on this type of reaction process [116]. It addresses the formation of a-acyloxycarboxamides, which constitute a class of very versatile synthons in organic chemistry. In the present context, this reaction was utilized by Schmidt and collaborators for the elaboration of intermediate 234 [117], a key fragment for the synthesis of the prolyl endopeptidase inhibitor Eurystatin A 231 (Scheme 12.33) [118]. 

The role of the zwitterion intermediate 164 and its rearrangement in the photocyclization of aromatic thioethers 163 to arene dihydro thiophene derivatives 165 is supported [81] by its independent trapping (via 1,3-dipolar cycloaddition) with biphenyl maleimide to obtain 166 in high yields (Scheme 8.47). 

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