Electrocyclic thermal

The electrocyclic thermal cleavage of four bicyclic (Y)-diaziridines 13 to their corresponding ( )- and (Z)-imides 14 and 15 has been studied (Scheme 2). kb initio calculations were carried out at UB3LYP/6-311-I—l-G (3df, 2p) levels of theory with the most favored product being 14 (2x-i) <2006JMT(770)7>. 

Thermal electrocyclizations of perhalogenated 1,3-butadienes yield perhalogenated cyclobutenes which can be solvolysed to 3,4-dihydroxy-3-cydobutene-l,2-dione ( squaric acid") and its derivatives (G. Maahs, 1966 H. Knorr, 1978 A.H. Schmidt, 1978). Double CO extrusion from fused cyclobutenediones has been used to produce cycloalkynes, e.g., benzyne from benzocyclobutenedione by irradiation in an argon matrix (O.L. Chapman, 1973) and cyc/o-Ci8, cyclo-Cn, etc. by laser desorption mass spectroscopy of appropriate precursors (see section 4.9.8). 

The direct connection of rings A and D at C l cannot be achieved by enamine or sul> fide couplings. This reaction has been carried out in almost quantitative yield by electrocyclic reactions of A/D Secocorrinoid metal complexes and constitutes a magnificent application of the Woodward-Hoffmann rules. First an antarafacial hydrogen shift from C-19 to C-1 is induced by light (sigmatropic 18-electron rearrangement), and second, a conrotatory thermally allowed cyclization of the mesoionic 16 rc-electron intermediate occurs. Only the A -trans-isomer is formed (A. Eschenmoser, 1974 A. Pfaltz, 1977). 

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

Buta-1,3-diene, 1 -(2 -furyl)-pyrolysis, 4, 600 Buta-1,3-diene, 1-mercapto-thiophenes from, 4, 887 Buta-1,3-diene, 1 -(1 -methyl-2-pyrrolyl)-thermal cyclization, 4, 285 Buta-1,3-diene, l-(2-thienyl)-electrocyclization, 4, 748 Butadienes... 

There are several general classes of pericyclic reactions for which orbital symmetry factors determine both the stereochemistry and relative reactivity. The first class that we will consider are electrocyclic reactions. An electrocyclic reaction is defined as the formation of a single bond between the ends of a linear conjugated system of n electrons and the reverse process. An example is the thermal ring opening of cyclobutenes to butadienes ... 

We have now considered three viewpoints from which thermal electrocyclic processes can be analyzed symmetry characteristics of the frontier orbitals, orbital correlation diagrams, and transition-state aromaticity. All arrive at the same conclusions about stereochemistiy of electrocyclic reactions. Reactions involving 4n + 2 electrons will be disrotatory and involve a Hiickel-type transition state, whereas those involving 4n electrons will be conrotatory and the orbital array will be of the Mobius type. These general principles serve to explain and correlate many specific experimental observations made both before and after the orbital symmetry mles were formulated. We will discuss a few representative examples in the following paragraphs. 

This compound is less stable than 5 and reverts to benzene with a half-life of about 2 days at 25°C, with AH = 23 kcal/mol. The observed kinetic stability of Dewar benzene is surprisingly high when one considers that its conversion to benzene is exothermic by 71 kcal/mol. The stability of Dewar benzene is intimately related to the orbital symmetry requirements for concerted electrocyclic transformations. The concerted thermal pathway should be conrotatory, since the reaction is the ring opening of a cyclobutene and therefore leads not to benzene, but to a highly strained Z,Z, -cyclohexatriene. A disrotatory process, which would lead directly to benzene, is forbidden. ... 

There are also examples of electrocyclic processes involving anionic species. Since the pentadienyl anion is a six-7c-electron system, thermal cyclization to a cyclopentenyl anion should be disrotatory. Examples of this electrocyclic reaction are rare. NMR studies of pentadienyl anions indicate that they are stable and do not tend to cyclize. Cyclooctadienyllithium provides an example where cyclization of a pentadienyl anion fragment does occur, with the first-order rate constant being 8.7 x 10 min . The stereochemistry of the ring closure is consistent with the expected disrotatory nature of the reaction. 

The thermal rearrangements of methyl-substituted cycloheptatrienes have been proposed to proceed by sigmatropic migration of the norcaradiene valence tautomer. The first step is an electrocyclization analogous to those discussed in Section 11.1. 

E. N. Marvell, Thermal Electrocyclic Reactions, Academic Press, New York, 1980. 

Perfluoroisobutylene undergoes cycloadditions with azides only at elevated temperatures, the reaction can lead to subsequent loss of nitrogen [6] (equation 4) In another high-temperature reaction, chlorotrifluoroethylene undergoes cy cloaddition with the azomethineylide generated from the thermal electrocyclic nng opening of an azindine, a reaction that contributes to a good overall synthesis of 3,4-difluoropyrroles [7] (equation 5)... 

The proposed mechanism for the Conrad-Limpach reaction is shown below. Condensation of an aniline with a 3-keto-ester (i.e., ethyl acetoacetate 5) with loss of water provides enamino-ester 6. Enolization furnishes 10 which undergoes thermal cyclization, analogous to the Gould-Jacobs reaction, via 6n electrocyclization to yield intermediate 11. Compound 11 suffers loss of alcohol followed by tautomerization to give 4-hydroxy-2-methylquinoline 7. An alternative to the proposed formation of 10 is ejection of alcohol from 6 furnishing ketene 13, which then undergoes 671 electrocyclization to provide 12. 

Synthesis of [d]-annelated indoles by thermal electrocyclic reactions 95MI7. 

Compound (Z)-51 and the corresponding ( ) isomer have also been studied as substrates in thermally and photochemically induced electrocyclizations leading to... 

Upon treatment of a divinyl ketone 1 with a protic acid or a Lewis acid, an electrocyclic ring closure can take place to yield a cyclopentenone 3. This reaction is called the Nazarov cyclization Protonation at the carbonyl oxygen of the divinyl ketone 1 leads to formation of a hydroxypentadienyl cation 2, which can undergo a thermally allowed, conrotatory electrocyclic ring closure reaction to give a cyclopentenyl cation 4. Through subsequent loss of a proton a mixture of isomeric cyclopentenones 5 and 6 is obtained ... 

The most striking feature of electrocyclic reactions is their stereochemistry. For example, (2 ,4Z,6 )-2,4,6-octatriene yields only c/s-5,6-dimethyl-l,3-cyclo-hexadiene when heated, and (2 ,4Z,6Z)-2,4,6-octatriene yields only trnns-5,6-dimethyl-l,3-cyclohexadiene. Remarkably, however, the stereochemical results change completely when the reactions are carried out under what are called photochemical, rather than thermal, conditions. Irradiation, or photolysis,... 

A similar result is obtained for the thermal electrocyclic ring-opening of 3,4-dimethylcyclobutene. The trans isomer yields only (2 ,4 )-2,4-hexadiene when heated, and the cis isomer yields only (2 ,4Z)-2,4-hexadiene. On UV irradiation, however, the results are opposite. Cyclization of the 2E,4 isomer under photochemical conditions yields cis product (Figure 30.4). 

Thermal and photochemical electrocyclic reactions always take place with opposite stereochemistry because the symmetries of the frontier orbitals are always different. Table 30.1 gives some simple rules that make it possible to predict the stereochemistry of electrocyclic reactions. 

Fora [4 + 2 -7r-electron cycloaddition (Diels-Aldei reaction), let s arbitrarily select the diene LUMO and the alkene HOMO. The symmetries of the two ground-slate orbitals are such that bonding of the terminal lobes can occur with suprafacial geometry (Figure 30.9), so the Diels-Alder reaction takes place readily under thermal conditions. Note that, as with electrocyclic reactions, we need be concerned only with the terminal lobes. For purposes of prediction, interactions among the interior lobes need not be considered. 

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

The thermal addition of dimethyl acetylenedicarboxylate to indoles, unlike the photocycloaddition (see Section 3.2.1.4.1.1.), proceeds via a polar stepwise process to yield, initially, 3,4-benzo-2-azabicyclo[3.2.0]hepta-3,6-dienes which in some cases are isolable,13 141 but which, in general, ring open in situ to give the indolylacrylates 3 and/or undergo electrocyclic ring expansion to 1-benzazepines.21... 

The thermally induced electrocyclic ring opening of 2-alkyl- and 2-acyl-3.4-benzo-2-azabicyclo-[3.2.0]hepta-3,6-dienes 2 to l//-l-benzazepines 1 (see Section 3.2.1.4.1.1.) are photorever-sible.23,37 38 Also, l-acyl-1//-benzazepines 1 (R = acyl), in refluxing xylene in the presence of silver(I) tetrafluoroborate, are in thermal equilibrium with their valence isomers the 2-acyl-3,4-benzo-2-azabicyclo[3.2.Oj nepia-3,6-uienes 2 (R = acyl).23-38... 

Similarly, enamino vinyl sulfones (345) can undergo a thermally allowed electrocyclic reaction between the termini of the enaminic double bond and the allyl sulfonyl portion in the intermediate anion (346) to afford a, /1-unsaturated thiene dioxides (348) as shown in equation 126335. 

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... 

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