Conrotatory electrocyclic ring opening

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). 

Cyclopropyl ions and radicals (23) can undergo conversion to allyl (24) by typical electrocyclic ring opening processes we have carried out calculations for ring opening by both conrotatory and disrotatory paths. Table 5 shows calculated activation energies for the various processes. 

In practice, the equivalent synthon of 2 was l-cyano-4,5-dimethoxybenzocyclobutene 22 (Scheme 3.7) which on heating generates a reactive o-quinodimethane by a conrotatory electrocyclic ring opening process (Cf. Scheme 3.7) and reacts, at 150-160 °C, with the 3,4-dihydroisoquinoleine 23 to give 80-88%yield of 13-cyanoprotoberberine 24. A simple reductive decyanation with lithium in liquid ammonia in the presence of isopropyl alcohol afforded xylopinine (19) in 84.6% yield [19]. 

Intermediates (6) can yield to the corresponding [3-lactams via conrotatory electrocyclic closures (Fig. 3). The main features of these transition structures closely resemble those found for the thermal electrocyclic ring opening of cyclobutenes [34]. 

Consider the electrocyclic ring-opening reaction of cyclobutene. The molecule is formally divided into two fragments the double bond and the single 0 bond which is cleaved.9 The frontier orbital interactions (0,7t ) and (0, it) relevant to the conrota-tory and disrotatory reactions are given in diagrams 4, 5, 6 and 7, respectively. The net overlap is positive for 4 and 5, but zero for 6 and 7. The conrotatory process is therefore allowed, and the disrotatory process forbidden. 

We can now go back to the reaction that introduced this section—the photochemical electrocyclic ring opening of ergosterol to give provitamin D2. By looking at the starting material and product we can deduce whether the reaction is conrotatory or disrotatory. 

There are two things to note here—firstly, the geometry of the double bond is nothing to do with whether the reaction is conrotatory or disrotatory. As you know, this 4re electron electrocyclic ring opening must be conrotatory. but as there is no substituent on the other end of. the diene product we can t tell. Secondly, notice that, in this 12-membered ring, a trans double bond is not only possible, but probably preferred. We introduced irradiation as a means of interconverting double bond isomers in Chapter 31. 

The electrocyclic reactions of phenyl fulgides and l,8a-DHNs can be photo-induced by a conrotatory process. The electrocyclic ring-opening reaction of cyclohexadiene systems (l,8a-DHNs) can also be induced thermally via a disrota-tory process. 

For the synthesis of estradiol methyl ether 4-319, the cyclobutene derivative 4-317 was heated to give the orthoquinonedimethane 4-318 which cydized in an intramolecular Diels-Alder reaction [109]. The thermally permitted, conrotatory electrocyclic ring-opening of benzocyclobutenes [110] with subsequent intramolecular cycloaddition also allowed the formation of numerous complex frameworks (Scheme 4.70). 

Sorensen and coworkers used a domino conrotatory electrocyclic ring-opening/ 6it-disrotatory electrocyclization for the formation of ring C in the total synthesis of ( )-viridin (4-327) (Scheme 4.72) [112]. Heating 4-325 in the presence of a base followed by in-situ oxidation with DDQ afforded the tetracycle 4-326 in 83% yield. 

Disrotatory and conrotatory rotation The concerted rotation around two bonds in the same direction, either clockwise or counterclockwise, is described as conrotatory. In the electrocyclic ring opening, the terminal p-orbitals rotate (or twist, roughly 90°) in the same direction known as conrotation (comparable to antarafacial) to form a new ct-bond. In disrotatory cyclization (comparable to suprafacial) the terminal p-orbitals rotate in opposite directions. These two modes of the electrocyclic reaction are shown in Fig. 8.37. 

The biosynthesis of vitamin D3 (8.24) involves the thermal [1,7]-sigmatropic rearrangement of pre-vitamin 8.23, which is obtained by conrotatory electrocyclic ring opening of 7-dehydrocholesterol (8.22) (Scheme 8.3). 

The photochemical transformation is a 6tt electron (4n + 2) electrocyclic ring opening. The selection rules predict a conrotatory process as illustrated ... 

Consider the electrocyclic ring opening of trans-3,4-dimethylcyclobutene. This compound opens in a conrotatory fashion under thermal conditions. Two products might be obtained from conrotatory ring openings allowed by the Woodward-Hoffman rules, but in fact only the trans.trans product is obtained because there are severe steric interactions in the TS leading to the cis,cis product. 

Stereochemical labels on the cyclobutene confirm that this 4-electron electrocyclic ring opening is conrotatory. Another way to view the reaction is from the closure of the diene. The ends of the HOMO of the diene must rotate con to create a bonding overlap for the new sigma bond. Because of microscopic reversibility, opening and closure follow the same route if the opening is conrotatory, then the closure will likewise be con. 

Figure 33 shows molecular orbital correlation diagrams for the disrotatory (51) and conrotatory (52) electrocyclic ring opening pathways for cyclobutene. With a total of four... 

---