Ring openings, electrocyclic

The concept of electrocyclic ring opening of a 1,2-dihydro six-membered heterocycles is familiar from the numerous examples found after nucleophilic attack, especially on cationic rings. Similar reactions occur with isolated 1,2-dihydro derivatives. Dihydropyridines can undergo isomerization by electrocyclic ring opening (see Equation 10). 1 -Vinyl- 1,2-dihydropyridines in a somewhat similar sequence yield pyridines via azacycloocatrienes (Equation 11). 

The 4-benzylpyran (501) rearranges on irriadiation or thermally into the 2-benzyl isomer (502) which yields the benzene (503) via electrocyclic ring opening. Irradiation of 2//-chromenes (504) gives an intense red color due to the quininoid photoproduct (505). 

6 Proton loss to an eight-it-electron conjugated system 

Very strong bases can extract a proton from the 1,2- or 1,4-dihydropyridine ring giving a fully conjugated eight-7T-electron antiaromatic system, which can be trapped by electrophiles. 

Reissert compounds (cf Section 3.2.1.6.8.iv) can be deprotonated (NaH/HCONMe2) to give anions (e.g. 507) which react with electrophiles to give intermediates (508) which can be hydrolyzed to substituted heterocycles (509). Electrophiles utilized include alkyl and reactive aryl halides and carbonyl compounds. 

---

The cyclohexadiene-hexatriene system seems to be less complicated than the cyclobutene-butadiene system. Cyclohexadiene undergoes photochemical electrocyclic ring opening ... 

Results of studies of the electrocyclic ring opening of 3 fluoro-, 3,3-difluoro-, and 3-tnfluoromethylcyclobutene are consistent with the theoretical predictions of the effect of fluonne on this reaction [142] Surpnsingly, fluonnated analogues of hexa tnene-cyclohexadiene systems undergo complex rearrangements mainly via free radical mechanisms and not by electrocyclic nng operung as expected [143] (equation 35)... 

By a photochemically induced elimination of CO, a chromium carbene complex with a free coordination site is generated. That species can coordinate to an alkyne, to give the alkyne-chromium carbonyl complex 4. The next step is likely to be a cycloaddition reaction leading to a four-membered ring compound 5. A subsequent electrocyclic ring opening and the insertion of CO leads to the vinylketene complex 6 ... 

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). 

Compound 6 is a pivotal intermediate in Schreiber s synthesis. It was hoped that the conspicuous and strained bridgehead cyclobutene substructure in 6 would undergo a conrotatory electrocyclic ring opening upon thermolysis to give an isomeric 1,3-diene (8, Scheme 1). In the event, when a solution of cyclobutene 6 in toluene is confined to a sealed tube and heated to 180°C for 12 h, a stereoisomeric mixture of 1,3-dienes 7 and 8 is produced in an excellent yield of 95% (7 8 ca. 5 1). Finally, irradiation of the 5 1 mixture of cis-7 and trans-8, or of each independently, establishes a photostationary state in which the desired trans isomer 8 predominates (8 7 ca. 10 1). 

Diels-Alder cycloaddition of 2/f-azirines 23 with cyclopentadienones provides 3//-azepines 25 in excellent yields by electrocyclic ring opening, with concomitant loss of carbon monoxide, of the initially formed, nonisolable cycloadducts 24, followed by a [1,5]-H shift in the resulting 2//-azepines.31 108... 

Azabicyclo[3.2.0]hepta-3,6-dienes are the 4 5 bicyclic valence isomers of 1//-azepines. In some cases there is an equilibrium between the bicycle and the azepine, whereas with other 1//-azepines photolysis yields an azabicycloheptadiene that can be isolated and characterized. For example, ethyl 2-azabicyclo[3.2.0]hepta-3,6-diene-2-carboxylate (1), the photoinduced valence isomer of ethyl l//-azepine-l-carboxylate (2), undergoes a clean, exothermic, first order, electrocyclic ring opening (AG = 20 kJ mol-1) to the parent 1//-azepine 2 on heating at 113-143C in an inert solvent (e.g., hexadecane).101... 

Azabicyclo[4.1.0]hept-3-enes, e. g. 13, are available from 1,4-dihydrobenzenes 12 by the route indicated, and are useful precursors for the synthesis of specifically substituted 1//-azepines free from isomeric contamination.61 For example, low temperature addition of bromine to bicycle 13 yields the dibromo derivative 14 which, with powdered sodium methoxide in tet-rahydrofuran, undergoes a double dehydrobromination followed by electrocyclic ring opening of the resulting 7-azabicyclo[4.1.0]hepta-2,4-diene 15 to give methyl l//-azepine-l-carboxylate (16). 

The intermolecular process is employed almost exclusively for the preparation of 1H-azepines and in most cases involves addition of a singlet nitrene133 to the arene to give, initially, an unstable 7-azabicyclo[4.1.0]hepta-2,4-diene (benzaziridine) intermediate, e. g. 1, which undergoes an electrocyclic ring opening to the l//-azepine, e. g. 2. 

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... 

Irradiation of triazafulvene 2 or 3 leads to the formation of an azacyclobutadienc intermediate which, after dimerization and two subsequent electrocyclic ring-opening reactions, gives the hexaphenyl-substituted 1.5-diazocine.48,49... 

A general entry into the azonine system, c.g. 4, is by photoinduced electrocyclic ring opening of the bicyclic valence isomer 3,9 11-13 which is readily prepared by earboethoxynitrene addition to cyclooctatetraene. 

Sporadic reports of the 2//-thiopyran transformation are still available. The electrocyclic ring-opening of 2-benzyl-2,4,6-triphenyl-2//-thiopyran (131, X = PhCH2) was detected by laser flash spectroscopy (86MI1). 2-Amino-2//-thiopyran was predicted to be more stable than its valence-bond isomer on the basis of semiempirical MINDO/3 and MNDO calculations (84JPR955). 

The stereochemistry of the electrocyclic ring opening following the attack of the nucleophile on the vinylic carbon appears to be governed by the principle of least motion159,60. 

Formation of 59 and 60 is postulated to occur via an electrocyclic ring opening reaction giving the open chain cation 63 which can then go either... 

The other commonly quoted industrial photochemical process is the production of vitamin D3 involving a photochemical electrocyclic ring opening followed by a thermal 1,7-hydride shift (Scheme 7.2). This is a further example of a successful low quantum yield process in this case there is no viable thermal alternative. Vitamin A acetate has also been produced commercially using a photochemical isomerization process to convert a mixed tetra-alkene precursor to the all-trans form. 

Pyrans and napthopyrans (chromenes) are photochromic compounds that undergo photochemically induced electrocyclic ring opening to give colored ortho-quinone methides.95-98 For example, chromene 153 opens on irradiation to give 154 (Eq. 1.41). 

Table 13-1. Computed reaction barriers and isomer stabilities [kcal/mol] for the electrocyclic ring opening of cyclobutene (relative to cyclobutene 1, including zero-point vibrational contributions). Except for G2, the results were obtained using the 6-311+G(d,p) basis set.

A domino process based on the twofold addition of alkenyl anions to a squarate ester was used by Paquette and coworkers [96] for the total synthesis of the triqui-nane sesquiterpene hypnophilin (4-284). The three-component reaction of 4-281,4-282 and vinyl lithium gave primarily the trans- and cis-adducts A and B, which furnished D either by an electrocyclic ring opening/ring closure via C or a dianionic oxy-Cope rearrangement (Scheme 4.60). Further transformations led to E and F, which resulted in the formation of 4-283 on treatment with acid. 

The forerunner in the Co-catalyzed [2+2+2] cycloaddition domino processes was that identified by Vollhardt and colleagues [273], with their excellent synthesis of steroids. Reaction of 6/4-1 with [CpCo(CO)2] gave compound 6/4-3 with an aromatic ring B via the intermediate 6/4-2. In this process, trimerization of the three alkyne moieties first takes place, and this is followed by an electrocyclic ring opening of the formed cyclobutene to give o-quinodimethane. This then undergoes a Diels-Alder reaction to provide the steroid 6/4-3 (Scheme 6/4.1). 

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

---