Electrocyclic rearrangement

The electrocyclic ring opening of heavily substituted cyclobutene derivatives which was investigated by Plieninger et al. [113], shows negative volumes of activation of 

A different type of known rearrangement is the electrocyclic rearrangement. This takes place for example for 1,3,5 trienes, which are converted to 1,3 cyclohexadienes when heated, as follows  

To determine if encapsulation in 1 affected the rate of the unimolecular rearrangement, various enammonium cations were prepared and the rates of rearrangement 

Analysis of the activation parameters for the different encapsulated substrates reveals that the source of catalysis is more complex than simply a reduction of the entropy of activation, since different effects are observed for substrates 26,27,30. While the rate acceleration for the encapsulated 26 was exclusively due to lowering the entropic barrier, for 27 and 30 a decrease in the enthalpic barrier for rearrangement is observed in addition. It is possible that, for 27 and 30 binding into the narrow confines of the metal-ligand assembly induces some strain on the bound molecules, thereby raising their ground-state energies compared to those of the unbound 

Although the [3,3] sigmatropic rearrangement was occurring inside 1, the question of the nature of the hydrolysis remained - does water enter the host cavity and hydrolyze the iminium inside of the assembly or is the iminium cation ejected and hydrolyzed in solution To further understand the hydrolysis mechanism, the 

From a series of experiments in solutions of pD varying from 6.5 to 12.8 and six equivalents of XMe.b, the buildup and hydrolysis of the iminium cationic intermediate was studied in the rearrangement and hydrolysis of [33 C 1] . In neutral pD (pD 6.5-8), the rates of iminium hydrolysis are essentially constant, with water acting as the nucleophile. However, in more basic solution, a dependence on [OD ] is observed until approximately pD 11, at which point saturation is observed. The observed linear first-order dependence on hydroxide concentration from the pD rage of 9-10.5 supports the mechanistic model where the iminium cation is ejected from the assembly and then hydrolyzed in solution. The presence of saturation implies that, after pD 11, the rate of iminium dissociation from 1 becomes rate limiting because hydrolysis becomes faster than the re-encapsulation process. 

The encapsulated enammonium substrate rearranges inside of 1 to form the iminium cation. The rearrangement step, as anticipated, is independent of [OD ] or [NMe4+]. The iminium product can reversibly dissociate from 1 to the exterior of the assembly where it is tightly ion associated. In the presence of a suitable ion 

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These reactions, called electrocyclic rearrangements, take place by pericyclic mechanisms. The evidence comes from stereochemical studies, which show a remarkable stereospecificity whose direction depends on whether the reaction is induced by heat or light. For example, it was found for the thermal reaction that cis-3,4-dimethylcyclobutene gave only cw,tran5-2,4-hexadiene, while the trans isomer gave only the trans-trans diene... 

In a number of rearrangements of siienes the Si=C bnd has been observed to react with a C—H bond of a methyl group that is usually attached at the ortho position of an adjacent mesityl group. Formally, these can be regarded as 2tt + 2cr reactions, although other descriptions may be possible. For example, a 1,5-H shift followed by an electrocyclic rearrangement of a Si=C with a C=C would effect the same results. Little is known about the mechanisms involved. Several examples of these types of reaction are described below, some being effected photochemically and some thermally. 

Brook et al. 5X1 observed such reactions during the formation of siienes by photolysis. Using radiation with A > 360 nm, they photolyzed acylsi-lanes such as 127, which bears a mesityl group attached to the carbonyl carbon. On prolonged photolysis of the initially formed silene 128, the C—H bond of the ortho methyl group of the mesityl group added to the silicon-carbon double bond to form the benzocyclobutane 129. Alternatively a 1,5-H shift would lead to the species 130, which would also yield the benzocyclobutane on electrocyclic rearrangement. 

One surprising feature emerged from the reactions of methanesul-phonyl azides with aromatic solvents at 120 °C, and that was the total absence of any IV-sulphonylazepine derivatives (45) from the reaction products. The latter would have been expected from the electrocyclic rearrangement of 42 of the same type as had been observed in the reac-... 

Reaction of 2-amino-benzyl alcohol and 2-chloroH-phcnylaminopyrimidinc forms the intermediate cation 204, which contains ene and iminium functionalities and undergoes electrocyclic rearrangement to the 2-phenylamino-6//-pynmido[2,l-2 ]quinazoline 205 (Scheme 32). The cation 204 is stabilized by the aryl groups. The 2-NHPh stmcture of the product was confirmed by 111 NMR spectroscopy <2002TL1303>. 

Note that the observed high stereospecificity of the reactions in equations (70) and (71) also points to a rapid coupling of ion pair after the electrocyclic rearrangement of the DBC cation radicals in the contact ion pairs. 

SCHEME 22 Activation and reaction volumes of electrocyclic rearrangements... 

The formation of cycloheptadienones from alkoxy(cyclopropyl)carbene complexes and alkynes (Entry 5, Table 2.24) [388,389] proceeds essentially by the same mechanism as the Dotz benzannulation reaction (see Figure 2.32). The cyclopropyl group participates in the electrocyclic rearrangement as the equivalent of a vinyl group. 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butvl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyclic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney nickel. Saponiflcation of intermediate 182 affords bromfenac (183) [46J. 

Construction of the closely related NSAID bromefenac (46-8) depends on the Gassman indolone synthesis [46] for incorporation of the acetic acid chain. That reaction involves an anion-initiated electrocyclic rearrangement related conceptually to the little-known Hauser ortho substitution rearrangement. The simplest example of the latter depends on the formation of a carbanion by abstraction of one of the acidic protons from a benzyltrimethyl quaternary salt to give I (the... 

The [W2S+W4S] electrocyclic rearrangement of the deuterated anft-2-azatri cycloheptane (66) at 350 °C yields 1 -methoxycarbonyl-6,7-dihydro-1//- azepine in which the deuterium is statistically distributed between the C-2, C-3, C-6 and C-7 positions. Presumably at 350 °C rapid 1,5-H(D) shifts are taking place involving the thermodynamically less stable 2,7-dihydro-lfT-azepine (67) (73JA7320). 

Thermal extrusion of a sulfur atom is the most common thermal reaction of a thiepin. The mechanism of this thermal process involves two orbital symmetry controlled reactions (69CC1167). The initial concerted step involving a reversible disrotatory electrocyclic rearrangement is followed by a concerted cheleotropic elimination of sulfur (Scheme 29). Similar aromatization reactions occur with thiepin 1-oxides and thiepin 1,1-dioxides, accompanied by the extrusion of sulfur monoxide and sulfur dioxide respectively. Since only a summary of the major factors influencing the thermal stability of thiepins was given in Section... 

Electrocyclic Rearrangements of Cyclobutenes and 1,3-Cyclohexadienes (4)5eco-1 /4/Detachment (4)cyc/o-1 /4/Attachment (6)5eco-1/6/Detachment (6)cycfo-1161 Attachment... 

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