Stereochemistry biradical -cycloaddition

Eq. 17 is meant to represent the possibility for a concerted formation of oxetane product. A problem that always exist in cycloadditions is the question of whether the reaction takes place by a two-step biradical reaction pathway or through a concerted mechanism. Such questions have not even been resolved for purely thermal reactions. 4> A recent speculation on this point proposes almost universal concertedness for all cycloaddition reactions. 79> In that work, mixed stereochemistry in the products of [2+2] cycloaddition reactions is generally attributed to a mixture of two concerted reactions, suprafacial-suprafacial, and supra-facial-antarafacial. It will be seen later that the PMO calculations generally do not support this idea. A mixture of biradical and concerted reactions is in better agreement with experimental facts. 

If one examines the minimal sequences of reaction steps for [2+2] cycloadditions, Eqs. 12—18, 32—35, one concludes that stereochemistry of addition, and perhaps relative reactivities might be calculable at several points. Oriented complexes could control regiospecificity, or the transition state leading to a biradical could be the important stage. Relative rates of product formation would be derived from relative perturbation stabilization energies for different configurations of the two reactants. 

A study of the stereochemistry and secondary isotope effects for the 2 + 2-cycloaddition of alkyl-substituted buta-1,3-dienes with Ceo indicates the formation of an open biradical intermediate in the rate-determining step leading to the cycloadduct (18) (Scheme 5). The addition of benzyne to C70 produces four isomeric monoadducts. One of these adducts is the first example of an adduct of a 5-6 ring fusion where the ring-fusion bond remains intact. 

All of the photochemical cycloaddition reactions of the stilbenes are presumed to occur via excited state ir-ir type complexes (excimers, exciplexes, or excited charge-transfer complexes). Both the ground state and excited state complexes of t-1 are more stable than expected on the basis of redox potentials and singlet energy. Exciplex formation helps overcome the entropic problems associated with a bimolecular cycloaddition process and predetermines the adduct stereochemistry. Formation of an excited state complex is a necessary, but not a sufficient condition for cycloaddition. In fact, increased exciplex stability can result in decreased quantum yields for cycloaddition, due to an increased barrier for covalent bond formation (Fig. 2). The cycloaddition reactions of t-1 proceed with complete retention of stilbene and alkene photochemistry, indicative of either a concerted or short-lived singlet biradical mechanism. The observation of acyclic adduct formation in the reactions of It with nonconjugated dienes supports the biradical mechanism. 

Also known are 2 + 2 cycloadditions proceeding by way of a bipolar ion, path (b) of Scheme l.28 These reactions occur in situations such as that depicted in Equation 12.14, where the intermediate zwitterion (10) is strongly stabilized. Tetracyanoethylene adds by this mechanism to /Mnethoxyphenyl-,29 alkoxyl-,30 and cyclopropyl-31 substituted olefins. The additions show large solvent effects.32 Partial loss of stereochemistry occurs as in the biradical cases, but it is much less pronounced. 

Excellent regioselectivity and stereoselectivity has been achieved in each photocycloaddition mode [45 48], Regiochemistry and stereochemistry in the meta process is decided by the orientation of the addends in the exciplex and by stabilization of biradical intermediates having a change transfer (CT) character (6) by the substituents on the arene. Intermolecular meta cycloaddition of arenes with cycloalkenes proceeds with endo selectivity (7) (Scheme 5). In the ortho-process, selectivities can be controlled mainly by the substituents on the reactants. 

For easier comparison the result of the thermal reaction is included for compounds 46 and 47. As can be seen in the reaction scheme above direct photolysis of the pyrazolines 46 and 47 proceeds mainly with retention of the original stereochemistry in the cyclopropanes isolated. 48,49 and 50 however lead mainly to the inverted stereochemistry in the cyclopropanes. The singlet biradical 51 formed from 46—49 is therefore clearly not on the same energy surface as a, . possible singlet diradical in the carbene cycloaddition. However one knows today that singlet carbene cycloaddition is a concerted process, so no such diradical should be detectable. 

Additions to Cyclopentenones and Related Systems. (2 + 2)-Cycloadditions are reported following the irradiation of mixtures of alkyl and aryl 2-thioxo-3/f-benzoxazole-3-carboxylates with alkenes. Cycloaddition also occurs to the CS double bond. The photochemical additions of arylalkenes to 3-phenylcyclo-pentenone and 3-phenyl cyclohexenone have been studied. The regio- and stereochemistry observed in the additions has been rationalized in terms of the stability of the intermediate biradicals. Photocycloaddition of allene to the cyclopentenone derivative (6) in methylene chloride solution at — 78°C affords... 

In the selected instances of the observation of ring-opened products, copolymerization reactions, and the loss of dienophile stereochemistry in the [4 + 2] reactions of a,/3-unsaturated esters bearing an additional C-3 electron-withdrawing group as well as the lack of an observed rate dependency on the solvent polarity have led Hall and co-workers to conclude that such cycloadditions may proceed with the generation of biradical intermediates. However, such conclusions have been further cautioned by the detailed investigations of Hall and his co-workers in which they... 

The enone (92) is reactive in its triplet state and when irradiated in methylene chloride solution is converted into the tetracyclic compound (93). The reaction involves a step-wise process in which the biradical (94) is involved. This process is reminiscent of (2-i-2)-cycloaddition reactions where bonding occurs at the P-atom of the enone, and rather than completing the cyclization, hydrogen (or deuterium) abstraction occurs. A detailed stereochemical analysis of the system was carried out and proof of the stereochemistry of the final product (93) has been presented. 

Stereochemistry, substituent effects and activation parameters of most ketene reactions are consistent with a one-step cycloaddition polar effects of substituents and solvents, as well as the isotope effect, often require, however, that a fair amount of charge separation (that is, unequal bond formation) characterises the transition state. It has been kinetically proved that cycloadditions of enamines to ketenes can also proceed through a dipolar intermediate this is so for the reaction between dimethylketene and N-isobutenylpyrrolidine . In the latter case, the rate coefficient for the formation of the intermediate strongly depends on solvent polarity itacetonuriie/ cyclohexane = 560. Use of the Same criteria used for ketenes (as far as experimental data allow it) in the case of the 1,2-cycloadditions of fluorinated olefins results, instead, in the conclusion that a two-step biradical mechanism is operating. Results for 1,2-cycloaddition of sulfonyl isocyanates to olefins, cases (g) and (h) in Table 17, give indications of dipolar intermediates during the course of these reactions. 

Further details have been published of the cycloadditions of alkenylidenecyclo-propanes with 1-phenyl-1,3,5-triazoline-2,5-dione, which were discussed in detail in an earlier Report. The stereospecificity observed with chiral alkenylidenecyclo-propanes supports the proposal of a cycloaddition pathway involving an eight-electron (i.e. Mobius) transition state, [( +, 2 -I- 2) -I-, 2]. Partial or complete loss of stereochemistry, depending on temperature, is observed with chlorosulphonyl isocyanate, implying a dipolar intermediate, and l,l-dichloro-2,2-difluoroethylene appears to add via biradicals. ... 

Careful application of the three simple postulates listed above can yield insight into the mechanism and stereochemistry of biradical reactions as complex as the thermal dimerization of cis, irons-1,5-cyclooctadiene [26] or the isomerization of allyl-substituted cyclopropanes via internal [2 + 2]-cycloaddition [27]. An attempt to do so here would take us too far afield, in view of the ease with which biradical intermediates interconvert. Instead let us move on to the considerably more stereoselective cycloaddition of reactant pairs with complementary polarity, that proceeds stepwise along a zwitterionic pathway. [23]... 

The most studied case is that of a cyclic enone reacting with an olefin. In these systems several trends are observed. The reaction proceeds from T, which may be either n,iT or -IT,IT, and triplet biradicals are likely involved. Electron-rich olefins react more rapidly and add with predictable regiochemistry. Cis-trans stereochemistry in the olefin is lost in the cycloaddition, and trans fused rings can form. 

The stereochemistry of the dimerization products of l-adamantyl-3-chloroallene has been assigned.Although the dimerization of optically active cyclononadiene gives results which strongly support a [ 2s -f 2a] concerted cycloaddition, the possibility that an intermediate biradical is produced and reacts stereospecifically must also be considered. 

The stereochemistry for the electrocycHzation of one of these o-xylylenols is explained by Scheme 8 the lowest energy conformer of the triplet biradical is the one that decays to two xylylenols, one with the OH pointed out forming the cyclobutenol by conrotatory motion, and any Diels-Alder cycloaddition occurs by disrotatory motion.More specific examples are described in Reference 108. 

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