Diradicals regioselectivity

In 1982 the present author discovered cyclic orbital interactions in acyclic conjugation, and showed that the orbital phase continuity controls acyclic systems as well as the cyclic systems [23]. The orbital phase theory has thus far expanded and is still expanding the scope of its applications. Among some typical examples are included relative stabilities of cross vs linear polyenes and conjugated diradicals in the singlet and triplet states, spin preference of diradicals, regioselectivities, conformational stabilities, acute coordination angle in metal complexes, and so on. 

The reaction is stereospecific for at least some aliphatic ketones but not for aromatic carbonyls.197 This result suggests that the reactive excited state is a singlet for aliphatics and a triplets for aromatics. With aromatic ketones, the regioselectivity of addition can usually be predicted on the basis of formation of the more stable of the two possible diradical intermediates obtained by bond formation between oxygen and the alkene.198... 

A photochemical reaction of the silyl enol ether of acetophenone and benzaldehyde provided the 2,3-diphenyl-3-trimethylsilyloxyoxetane (13) with excellent regioselectivity (> 95 5) and diaster-eoselectivity (> 95 5) (91TL7037). In this example, the diastereoselection was explained by anti-approach of the two phenyl groups during the carbon-carbon bond forming step from the diradical intermediate (Scheme 7). 

Now we turn to selected examples of interest. One involves a multiplicity dependence of the regioselectivity. This is illustrated in Scheme 4. While one simplistically might write a single intermediate cyclopropyldicarbinyl diradical structure for both singlet and triplet multiplicity, the regioselectivity of unzipping depends on which species is involved37. 

An alternative two-step mechanism involving a spin-paired diradical intermediate has also been considered for 1,3-cycloadditions.18,68,69 However, ab initio calculations70-72 on a wide variety of 1,3-dipoles and dipolarophiles are found to coincide essentially with a synchronous 1,3-cycloaddition mechanism.15,17 On the other hand, a two-step mechanism passing through two transition states separated by an intermediate has been derived using the MINDO/3 method, and found to be compatible with substituent and solvent effects as well as stereospecificity observed in 1,3-cycloadditions.73 However, several factors beyond FMO interactions, such as closed shell repulsions, geometrical distortions, polarization, and secondary orbital interactions, all influence mechanisms, rates, and regioselectivities in cycloaddition reactions.74... 

Whereas FMO theory correctly predicts the regioselectivity for cycloadditions in simple alkyl-substituted olefinic systems,51,58 extension of similar calculations for cycloadducts (7a,b-lla,b)120 predicts the formation of regioisomer a, although, except in the case of 7 and 8, the b isomer is the predominant one. The differences between prediction and experiment in stereoselectivity have been attributed primarily to double bond rehybridization arising from double bond distortion in bridgehead olefins,142 which also explains their enhanced reactivity.96,120 Also double-bond deformation that will alter the normal mixing of alkyl substituent orbitals with localized rc-bond orbitals may explain the unexpected formation of 8b.120 Attempts to explain the formation of the b isomers, based on a two-step diradical mechanism, also have failed.120... 

Further experimental support for the effect of the fragmentation of the 1,4-diradical intermediates on the regioselectivity of the photocycloaddition was recently reported by Weedon and coworkers68 69, who obtained different H,H/H,T ratios between the photocycloproducts [H,H (93) and H,T (94)] and the trapped products 95-98, upon irradiation in the absence of H2Se in the former case and complete trapping of the diradical intermediates in the presence of H2Se in the latter case (Scheme 21). 

Schuster s and Weedon s results support Bauslaugh s proposed mechanism that emphasizes the effect of the ratio between cyclization and the alternative fragmentation pathway of the diradical intermediate, on the regioselectivity in the intermolecular photocycloadditions, and propose not to consider the oriented 7r-complex (exciplex) as an intermediate in the mechanistic pathway of the [2 + 2] photocycloaddition of enones to alkenes. 

Furthermore, Becker and coworkers81 have succeeded in trapping the 1,4-diradical intermediates 113 and 114 in the irradiation of compound 112 providing direct evidence for these intermediates and support for the regioselectivity in the first bond formation (Scheme 27). 

Abe, M., Kawakami, T., Ohata, S., Nozaki, K., and Nojima, M. (2004) Mechanism of Stereo- and regioselectivity in the Paterno-Buchi reaction of furan derivatives with aromatic carbonyl compounds Importance of the conformational distribution in the intermediary triplet 1,4-diradicals. Journal of the American Chemical Society, 126 (9), 2838—2846. 

If the reaction proceeds directly to a diradical intermediate, the regioselectivity with an unsymmetrical alkene will be determined from the relative stability of the possible diradical intermediates. Diradical 13 will be less stable 14. If on the other hand, the reaction proceeds from the exciplex, the orientation of alkene in the... 

It has been thought for some time that the interactions of triplet ketones with olefins involve a competition between hydrogen abstraction from, energy transfer to, and cycloaddition to the double bond 126>. Cycloaddition has generally been considered to proceed via a diradical intermediate. At first, the only evidence for a diradical was that the regioselectivity of oxetane formation often — but not always — is such as would be expected from the relative stabilities of the possible diradical intermediates 126>. Moreover, n,n ketone triplets are known to act like alkoxy radicals, which add to olefins, albeit less efficiently than do most other... 

It is assumed that a CT complex precedes diradical formation 140,143,146). primarily because of the regioselectivity of addition to unsymmetrical olefins. If different complexes are indeed involved, the final product ratio is a complex function of many competing rates. For example, let us assume the least complicated scheme as shown below for cyclopentenone. 

We are far from exhausting the subject of regioselectivity in dipolar cycloadditions with these few examples. Frontier orbital theory, for all its success in accounting for most of the otherwise bewildering trends in regioselectivity, is still fundamentally defective. We should keep in mind that the frontier orbitals used here must reflect some deeper forces than those that we are taking into account in this essentially superficial approach. Nevertheless, no other easily assimilated theory, whether based on polar or steric factors, or on the possibility of diradical intermediates, has had anything like such success. 

However, the photocycloaddition of ketones to Z-substituted alkenes does not fit the explanation based on the relative stability of the diradicals. Irradiation of a solution of acrylonitrile 8.22 in acetone 8.21 gives the adduct 8.23, together with dimers of acrylonitrile. This regioselectivity is consistent with a frontier orbital argument. 

The observations are that a donor substituent, as in the benzonorbornene 8.65 forms the first bond to the meta position, which is best pictured as giving the diradical 8.66, and hence the tricyclic product 8.67. However, an electron-withdrawing group in the benzonorbornene 8.68 forms the first bond to the para position, which is best pictured as giving the diradical 8.69, and hence the tricyclic product 8.70. Both of these reactions are highly regioselective, yet the diradicals 8.66 and 8.69 are probably the less stable of the two possible radicals in each case. 

In contrast to the different regiochemistry seen in the photochemical ring closures of the benznorbornadienes 8.65 and 8.68, both benznorbomadienes 8.100 show the same regioselectivity, probably by way of the diradical 8.101. Explain this observation. 

The reaction proceeds via the triplet and the mechanism involves vinyl-vinyl rather than naphtho-vinyl bridging" . In the case of such triplet rearrangements, it has been shown" that the cyclopropyldicarbinyl diradicals (i.e. Diradical I) are actual reaction intermediates of finite lifetime and that, when two such alternative diradicals are possible, formation of the lower energy one determines the reaction regioselectivity". ... 

MO calculations that give tt-orbital coefficients for dienes and dienophiles are beyond the scope of this book. However, there is a simple mnemonic trick that will predict regioselectivity in many cases. It involves drawing the four possible diradical intermediates that can be formed by homolytic bonding at one end of each reactant. Always remember, this is just a mnemonic trick most Diels-Alder reactions are concerted and do not proceed through a diradical intermediate. 

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