Electrocyclization torquoselectivity

The formation of cyclic nitrones (150) from pericyclic mechanism. Kinetic and computational studies have provided evidence for the involvement of a novel pseudo-pericyclic electrocyclization in the conversion of o-vinylphenyl isocyanates into quinolin-2-ones. " Such reactions have also provided evidence of torquoselectivity in a 6jt system. Hash vacuum thermolysis of triazoles (151) has been found to afford dihydroquinolines (155), presumably by generation of a-oxoketenimines (152) which can undergo a [1,5]-hydrogen shift to the o-quinoid imines (153)7(154) and subsequent electrocyclization (see Scheme 57). 

Benzocyclobutenone and derivatives have been shown to react with diazomethylene anions to give 2,3-benzodiazepines under very mild conditions. A mechanism has been proposed which involves four-electron electrocyclic ring opening of the initial alkoxide, with important acceleration by the alkoxide anion. Torquoselectivity to set up an eight-electron electrocyclic ring closure to the benzodiazepine enolate has been attributed to the strong preference of the alkoxide anion for outward rotation. This mechanism has been supported by isolation of one of the /S-diazo alcohols, and its conversion to a benzodiazepine on LDA treatment.84... 

The Rondan-Houk theory rationalizes many experimental results and leads to several predictions which have since been confirmed. Exceptions have been explained by Houk and co-workers, using numerical calculations. In a sense, the problem of electrocyclic reaction torquoselectivity may be considered solved. 

Actually, the first example of torquoselectivity dates back to the 1960s, though it was not identified using this terminology. The solvolysis of cycloproyl halides and tosylates proceeds via a two-electron electrocyclic reaction to yield allyl cation. disrotatory pathways are allowed, only one occurs ... 

A six-electron cychzation will proceed with disrotatory motion. Torquoselectivity in a six-electron electrocyclic reaction was first examined in the ring opening... 

The concept of torquoselectivity is now accepted as an extension of the Woodward-Hoffman rules. It has been used as a guide for synthetic chemists to prepare the appropriate stereoisomer. Examples include Danishefsky s exploitation of the stereoselective ring opening of fran5 -l,2-disiloxybenzocyclobutenes 133 to prepare idarubicin, Paquette s use of the electrocyclization of 134 that ultimately leads to a very efficient synthesis of pentalene, and Murakami s ... 

There are many cases in which the torquoselectivity is not nearly so easy to explain or predict. For example, which diastereomer is predominantly obtained from the electrocyclic ring opening of c/,v-3-chloro-4-mcthylcy-clobutene The answer is not obvious. Steric effects could easily be offset by electronic effects. Calculations of TS energies can sometimes give reasonably good predictions. 

The Nazarov reaction, in which the key electrocyclic step is the conrotatory process 6.505, has one more atom in the ring but the same number of electrons. The question with respect to torquoselectivity now, since this reaction is taking place in the opposite direction, namely ring-closing, is which reacts faster, a dienone... 

Finally, the preferred direction of disrotatory ring closure has been addressed just as in the electrocyclic ring opening of cyclobutene. In the six-electron case, tt acceptor substituents control the direction of rotation in the same sense as in cyclobutene but the torquoselectivity effect is attenuated. Further, steric effects tend to play a bigger role, and both effects were attributed to the disrotatory nature of the transition state. 

Figure 9.6 Torquoselectivity the choice between the two rotation modes in electrocyclic ring openings.

Fig.2 Torquoselectivity in 4 r electrocyclic ring opening (thermal conditions) [57-64]...

The torquoselectivity of the 4 r electrocyclic ring-opening reaction of 2-azetines has been reported to be controlled by the Brpnsted acidity of the catalyst and the polarity of the solvent." A review of the origin of the torquoselectivity in the thermal ring opening of cyclobutenes based on the Cplex-isoelectronic theory and expanded Robinson electronic theory has been reported." Cplex-isoelectronic theory is said to provide a rational for the torquoselectivities in the ring opening of cyclobutenes." ... 

A stereoselective electrocyclization developed for the synthesis of reserpine results from a stereocentre six atoms away from the newly fornoing chiral centre that is responsible for the diastereoselectivity of the ring closure. The presence of allylic strain in the disfavoured transition state results in the torquoselective ring closure (Scheme 38). 

Computational studies of oxazolidinone-directed Nazarov cyclization show that the chiral oxazolidinone auxiliaries provide control over the torquoselectivity of 4n electrocyclic ring closure and the regioselectivity of subsequent deprotonation (Scheme 177). °... 

The formation of j8-lactams from aliphatic acid chlorides and imines has been reviewed. The reaction is assumed to proceed through in situ formation of a ketene, followed by interaction with the imine to form a zwitterionic intermediate, which undergoes an electrocyclic conrotatory ring closure to give the jS-lactam ring (Scheme 8). The stereoselectivity of the reaction is sensitive to both the electronic and steric effects of the substituents on the ( )- or (Z)-imine, and the former manifest themselves in the electronic torquoselectivity that occurs during the conrotating cyclization of a zwitterionic intermediate [shown for ( )-imine in Scheme 8]. ... 

Other examples of sequences where electrocyclization is the final step include the atom-economical syntheses of [4.6.4.6.] fenestradienes. A tandem hydrogenation/8 t-> 6 t electrocyclization cascade from en-yn-enes 110 linked to a preexistent cyclobutane-containing tricycle was developed (Scheme 5.40) [118, 119]. Overall yields for the sequence range from 63-93%, leading to these fenestradienes 112 with full diastereoselectivities. These results may be explained by the high torquoselectivities observed during the 8jt-conrotatory process that forms the cyclooctatrienering intermediate 111 [120]. 

Hulot, C., Amiri, S., Blond, G. L, Schreiner, P. R., Suffer , J. (2009). Understanding the torquoselectivity in 8x-electrocyclic cascade reactions synthesis of fenestradienes versus cyclooctatrienes. Journal of the American Chemical Society, 131, 13387-13398. 

Torquoselectivity is described as the preference of clockwise (38) or counterclockwise (39) rotation of substituents in an electrocyclization reaction, giving rise to... 

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