Torquoselectivity

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

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  

TABLE 4.15 Activation Free Energies for the Electrocyclic Ring Opening of 108 and 109  

TS energies are likely to be adequately estimated, especially the trends among related inward versus outward TS for a series of substituted cyclobutenes. They first examined the ring opening of iran -3,4-dimethylcyclobutene (116) and irani -B.d-dihydroxycyclobutene (117).2° °2 The outward rotation is favored over the inward for both cases. More importantly, while the inward barriers are similar, the outward barrier for 117 is 17 kcal mol lower than for 116, a difference not readily amenable to rationalization based solely on substituent size. 

TABLE 4.16 Activation Energies (kcal mol for 3-Substituted Cyclobutenes  

The observed product is the thermodynamic sink. Torquoselection is preserved according to this mechanism, and fully accounts for the experiment. 

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 

Another silicon-assisted kind of torquoselectivity is in the allylsilane-type of Nazarov cyclisation. Now there is chirality, and there is a high level of torquoselectivity in the sense shown by the allylsilane 6.507, determined by the chirality.957 

It is perhaps more simple to note that both the vinylsilane reaction 6.504 and the allylsilane reaction 6.507 are showing the normal pattern of stereochemistry for their reactions with electrophiles a preference for retention of configuration in the double bond geometry for a vinylsilane, and anti for an allylsilane, where anti refers to the side of the double bond to which the new bond is formed relative to the side on which the silyl group resides. In the product 6.509, the new C—C bond has formed to the lower surface of the left-hand double bond, while the silyl group was conjugated to the top surface in the allylsilane 6.508. 

Torquoselectivity in this series is a powerful force, overriding any steric clash of the two methyl groups moving towards each other. 

The isomeric cyclopropanes 6.527 and 6.529 lose fluoride and chloride, respectively, in spite of the much better nucleofugal properties of the latter. The sense of torquoselectivity is determined because only a U-shaped cation can be formed in the six-membered ring leading to the products 6.528 and 6.530, and this in turn determines which of the halide ions leaves.961 

The simplest explanation26 is to note that the transition structure for conrotatory opening with a filled p orbital inside 6.316 has a three-atom, four-electron conjugated system, which will be anti-aromatic, whereas an empty orbital inside 6.317 has a three-atom, two-electron conjugated system, which will be aromatic. Houk s calculations indicate that there is very little involvement of the p orbitals of the 7i bond in the transition structure, but even if they are included, the 

The reverse reaction of this general class—an allyl cation giving a cyclopropyl cation—is found in Favorskii rearrangements. The diastereoisomeric Q-chloro enolates 6.334 and 6.337 give the cyclopropanones 6.335 and 6.338, respectively. Thus the reaction is stereospecific, at least in a nonpolar solvent. Evidently the allyl cation is not formed, otherwise the two chlorides 

In a more polar solvent, Favorskii reactions cease to be stereospecific, and presumably take place by ionisation of the chloride to give the same cation from each diastereoisomer. Whether the reaction takes place by way of the cation or with concerted loss of the chloride ion, this reaction presented a serious puzzle before its pericyclic nature was recognised. The a overlap of the p orbital on C-2 of the enolate with the p orbital at the other end of the allyl cation 6.340 or with the orbital of the C—Cl bond 6.341 looked forbiddingly unlikely—it is 3-endo-trig at C-2. It is made possible by its pericyclic nature, where the tilt of the orbitals can begin to sense the development of overlap. The torquoselectivity in the development of overlap 6.341, however improbable it looks, corresponds to inversion of configuration at the carbon atom from which the chloride departs. 

Account for the change of product ratio in the following reaction as a result of the change of solvent from polar to nonpolar (note that the solvents are inert in the conditions used for these reactions). 

Assign the following thermal pericyclic reactions to their class, and predict the relative stereochemistry of the products.27 

In the conrotatory ring openings of substituted cyclobutenes, the transition states have been calculated to be antiaromatic when a filled p-orbital moves inside leading to a three-center four-electron conjugated system as in 57 — cis-58 and aromatic when an empty orbital moves inside leading to a three-center two-electron conjugated system as in 61 62 and 63 65 [24]. 

The torquoselectivity on account of electronic effects is less pronounced in the disrotatory ring opening of 5,6-disubstituted 1,3-hexadienes. The effect is rather more steric in nature than electronic, and the larger substituents move outward [25, 26]. For instance, a hexatriene with both 1- and 6-substituents on trans-double bonds reacts faster than a hexatriene with one substituent on a trans-double bond and the other substituent on a s-double bond. The transformation 66 — 67 has been estimated to proceed 20 times faster than the transformation 68 — 69 under otherwise identical reaction conditions. 

Electronics overcomes sterics-selective even for bulky substituents  

The antiperiplanar orbital arrangement in the outward rotation maximizes the interaction between the donor orbital of the substituent and o -orbital of the stretched cyclobutene bond (the LUMO of the transition state). As a result, the outward rotation is preferred by the donor substituents. On the other hand, acceptor substituents with a low-lying vacant orbital prefer an inward comotation, where this orbital overlaps directly with the a-orbital of the stretched bond (the HOMO of the transition state). Both of these effects correspond to a two-electron interaction and stabilize the transition state. 

Orbitals from the breaking bond have to be antiperiplanar to the leaving OTs group 

Methyl groups rotate inside (towards each other) 

2 Diastereoselection in nucleophilic addition to carbonyl compounds and other jr-systems 

At the same time that these stereochemical results were being studied, some interesting substituent effects on the reaction rates were noticed. For example, 3-formylcyclobutene has an activation energy that is over 5 kcal / mol smaller than the parent hydrocarbon. The effects are substantial, and they have been the topic of considerable investigation. Dolbier, 

Substituent orbital filled for donor empty for acceptor 

Unfavorable closed-shell repulsion for donor favorable mixing of empty with filled for acceptor 

No ch lnce for favorable filled-empty interaction in donor case donor orbital is near node of j orbital 

D electron-donating substituents A electron-accepting substituents 

The products, Z-a-siloxyacrylic acids, are easily converted into polysubstituted y-lactones 70 by acidic treatment. This transformation can be carried out in one pot from the starting ketones 69 (Fig. 22). 

---

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... 

Trialkylsilyl vinyl ketenes (72) have been shown to react stereoselectively with a-benzotriazolyl organolithium species to give highly substituted cyclopentenones. The selectivity was found to be kinetic, not thermodynamic, in origin. Several possible mechanisms have been proposed (Scheme 10). It has been suggested that the observed stereoselectivity may result from torquoselectivity in a concerted reaction, or from stereospecific conrotatory cyclization of cation (73), formed stereoselectively because of the interaction shown between the electron-withdrawing group Z and the metal ion.75... 

Electron-accepting R groups are best represented by two low-lying orbitals, one filled and one empty. Figure 6.1 shows that the interaction of the HOMOs will inhibit the in pathway, whereas the HOMO (cyclobutene)-LUMO (R) interaction will promote it. The LUMO (cyclobutene)-HOMO (R) also disfavors the in pathway. These results are summarized in Figure 6.3 interaction (1) favors the in mode and interactions (2) and (3) impede it. This means that the energy gap between the cyclobutene HOMO and the R LUMO must be as small as possible for an in reaction to occur. In other words, R must be a powerful acceptor. However, Rondan and Houk believe that even then, interaction (3) may largely cancel interaction (1) and the torquoselectivity will not be very pronounced. 

A priori, we would expect disrotatory reactions to show poorer torquoselectivity than conrotatory reactions for two reasons. Consider, for example, the hexatriene cyclohexadiene interconversion. On the one hand, the overlap between R and the distal carbon C6 is similar for the in and out pathways, as in the in mode, the major lobe at C6 is oriented away from R ... 

On the other hand, hexatriene must take a helical structure.6 By analogy with the octatetraene case, it may be inferred that electronic effects will have a smaller influence and steric effects a larger influence than in the cyclobutene torquoselectivity. This is indeed what was found by Houk and co-workers.7... 

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. 

Explain the torquoselectivity in the following cyclobutene ring-opening reactions ... 

Photoirradiation at 300nm of iV-alkoxycarbonyl-l,2-dihydropyridines results in ring closure and the formation of 2-azabicyclo[2.2.0]hex-5-enes. Substituents are tolerated at the 2-, 3-, and 4-positions however, the yields are significantly lower than those for unsubstituted dihydropyridines. Irradiation of 2-substituted-l,2-dihydropyridines 112 proceeds via a torquoselective process to give only the endo-product 113 (Equation 5) <2001JOC1805, 2000T9227>. 

Like Roald Hoffmann and Ken s own Ph.D. adviser, R. B. Woodward, Ken seems to enjoy making up erudite-sounding names for new phenomena that he discovers. In addition to periselectivity and torquoselectivity , Ken has added theozyme to the chemical lexicon. 

Irradiation of 2-substituted-l,2-dihydropyridines 546 proceeds via a torquoselective process to give only the endo product 547 <2001JOC1805, 2000T9227>. 

---