Stereospecific electrocyclic

The stereoselective synthesis of (+)-trichodiene was accomplished by K.E. Harding and co-workers. The synthesis of this natural product posed a challenge, since it contains two adjacent quaternary stereocenters. For this reason, they chose a stereospecific electrocyclic reaction, the Nazarov cyclization, as the key ring-forming step to control the stereochemistry. The cyclization precursor was prepared by the Friedel-Crafts acylation of 1,4-dimethyl-1-cyclohexene with the appropriate acid chloride using SnCU as the catalyst. The Nazarov cyclization was not efficient under protic acid catalysis (e.g., TFA), but in the presence of excess boron trifluoride etherate high yield of the cyclized products was obtained. It is important to note that the mildness of the reaction conditions accounts for the fact that both of the products had an intact stereocenter at C2. Under harsher conditions, the formation of the C2-C3 enone was also observed. 

Electrocyclic reactions of 1,3,5-trienes lead to 1,3-cyclohexadienes. These ring closures also exhibit a high degree of stereospecificity. The ring closure is normally the favored reaction in this case, because the cyclic compound, which has six a bonds and two IT bonds, is thermodynamically more stable than the triene, which has five a and three ir bonds. The stereospecificity is illustrated with octatrienes 3 and 4. ,Z, -2,4,6-Octatriene (3) cyclizes only to cw-5,6-dimethyl-l,3-cyclohexadiene, whereas the , Z,Z-2,4,6-octa-triene (4) leads exclusively to the trans cyclohexadiene isomer. A point of particular importance regarding the stereochemistry of this reaction is that the groups at the termini of the triene system rotate in the opposite sense during the cyclization process. This mode... 

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... 

Apart from their intrinsic interest, these electrocyclic reactions have considerable synthetic carbon-carbon bond-forming importance because of their rigid stereospecificity, which is much greater than in the vast majority of other, non-concerted reactions involving biradical or bipolar intermediates. 

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. 

The simplest example of an electrocyclic reaction involving 4n electron system is the thermal opening of cyclobutenes to 1,3 butadienes. The reaction can be done thermally or photochemically and under either conditions, it is stereospecific. 

Although a few other acyclic examples of stereospecific isomerisation of hexatrienes are known, specially in the field of natural product like steroid chemistry, the commonest reactions of this type are in cyclic hexatrienes. Cyclooctatriene and cyclooctatetraene are systems in which the electrocyclic reaction goes very readily and they show an interesting trend. 

Thermal and photochemical electrocyclic reactions are both stereospecific, with the two processes giving rise to stereospecific reactions in the opposite sense. 

A striking feature of thermal electrocyclic reactions that proceed by concerted mechanisms is their high degree of stereospecificity. Thus when cis-3,4-dimethylcyclobutene is heated, it affords only one of the three possible... 

The cyclization step of Equation 28-8 is a photochemical counterpart of the electrocyclic reactions discussed in Section 21-10D. Many similar photochemical reactions of conjugated dienes and trienes are known, and they are of great interest because, like their thermal relatives, they often are stereospecific but tend to exhibit stereochemistry opposite to what is observed for formally similar thermal reactions. For example,... 

As a first example of an electrocyclic reaction illustrating stereochemistry, let us take the pair of conrotatory cyclobutene openings, showing that the reactions are stereospecific. 

A pentadienyl cation has the same number of ji-electrons as the allyl anion, and its electrocyclic reactions will be conrotatory. In terms of the Woodward-Hoffmann rule, it can be drawn 4.82 as an allowed [K4a] process. It has been shown to be fully stereospecific, with the stereo isomeric pentadienyl cations 4.83 and 4.85 giving the stereoisomeric cyclopentenyl cations 4.84 and 4.86 in conrotatory reactions, followed in their NMR spectra. 

This chapter follows on from chapter 12 where we introduced some basic ideas on stereocontrol. Since then we have met many stereospecific reactions such as pericyclic reactions including Diels-Alder (chapter 17), 2 + 2 photochemical cycloadditions (chapter 32), thermal (chapter 33) cycloadditions, and electrocyclic reactions (chapter 35). Then we have seen rearrangements where migration occurs with retention at the migrating group such as the Baeyer-Villiger (chapters 27 and 33), the Amdt-Eistert (chapter 31) and the pinacol (chapter 31). 

On the other hand, cation formation by decarboxylation of an acyloxonium cation RC02+ is supported by the partial stereospecificity observed in the electrolysis of cis- and trans-bicyclo [3.1.0] hexane-3-carboxylic acid 2°5 and the electrocyclic ring opening in the anodic oxidation of 3-methyl-2-phenylcyclopro-panecarboxylate (22, 23) to cyclopropyl methyl ether (24, 25) and allylic ethers (26, 27) (Eq. (97)) 206). 

The essential aspects of reaction (25) are depicted in Fig. 6. Huisgen et al. (1967) have provided a beautiful example of an odd electrocyclic change in (26). The aziridine opens up to a dipolar four-electron allylic species. Since the HOMO is b (Fig. 1), the thermal change is conrotatory and the excited state process is disrotatory. To avoid equilibration of the dipolar ions, these workers trap them with an acetylenic ester in a stereospecific cycloaddition, which we shall discuss presently. 

Let s begin by considering the simplest electrocyclic reaction, the thermally induced interconversion of a diene and a cyclobutene. As illustrated in the following example, the reaction is remarkably stereospecific, occurring only by a conrotatory motion ... 

Electrocyclic reactions of conjugated polyenes create chiral molecules through stereospecific conrotatory or disrotatory processes. In solution, the two enantiom-... 

Similarly, thermal (at 150°C) electrocyclic opening of cyclobutenes forms conjugated butadienes this mode of reaction is favoured by relief of ring strain. However, the reverse ring closure is not normally observed. Photochemical ring closure can be affected, but the stereospecificity is opposite to that of thermal ring opening. 

Stereochemistry Electrocyclic reactions, like all pericyclic processes, exhibit great stereospecificity. The stereospecificity of such reactions is demonstrated by thermal closure of fransjds,trans-2,4,6-octatriene (8.12) to ds-5,6-dimethyl-1,3-cyclohexadiene (8.13) and of the isomeric frans,cis,czs-octatriene (8.14) to frans-5,6-dimethyl-1,3-cyclohexadiene (8.15). 

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