Alkene also theory

In theory, three isoxazolines are capable of existence 2-isoxazoline (2), 3-isoxazoline and 4-isoxazoline. The position of the double bond may also be designated by the use of the prefix A with an appropriate numerical superscript. Of these only the 2-isoxazolines have been investigated in any detail. The preparation of the first isoxazoline, 3,5-diphenyl-2-isoxazoline, from the reaction of )3-chloro-)3-phenylpropiophenone with hydroxylamine was reported in 1895 (1895CB957). Two major syntheses of 2-isoxazolines are the cycloaddition of nitrile A-oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamine. Since 2-isoxazolines are readily oxidized to isoxazoles and possess some of the unique properties of isoxazoles, they also serve as key intermediates for the synthesis of other heterocycles and natural products. 

Frontier orbital theory can also explain the regioselectivity observed when both the diene and alkene are unsymmetrically substituted.4 Generally, there is a preference... 

Schindler and coworkers verified the formation of hydroxyl radicals kinetically and further RRKM calculations by Cremer and coworkers placed the overall concept on a more quantitative basis by verifying the measured amount of OH radical. An extensive series of calculations on substituted alkenes placed this overall decomposition mechanism and the involvement of carbonyl oxides in the ozonolysis of alkenes on a firm theoretical basis. The prodnction of OH radicals in solution phase was also snggested on the basis of a series of DFT calculations . Interestingly, both experiment and theory support a concerted [4 4- 2] cycloaddition for the ozone-acetylene reaction rather than a nonconcerted reaction involving biradical intermediates . 

Semiempirical calculations show that the approach of the dipolarophile in a head-to-head manner is 5.91 kcal/mol more favorable than the head-to-tail orientation with electron-rich alkenes (93). This difference is manifest in the ground state of resulting cycloadducts where the head-to-head adduct is 6.6 kcal/mol more stable. Similarly, the head-to-head transition state is more favorable by 3.4 kcal/mol for electron-poor alkenes, and 7.4 kcal/mol for electron-rich alkenes as calculated with density functional theory (91). This preference is also carried over into the ground-state energies of the resulting cycloadducts. 

Reactions of nitrile oxides with 1,1-disubstituted alkenes afford products in which the oxygen atom of the nitrile oxide gets attached to the most crowded carbon atom of the dipolarophile. This high regioselectivity does not seem to depend on the type of substituent present on the alkene (142-152). Some of the results cannot be satisfactorily interpreted on the basis of FMO theory (149,151). Both steric and electrostatic effects often counteract each other and contribute to the regioselectivity actually observed. With trisubstituted alkenes, the orientation of cycloaddition is apparently dominated by this phenomenon. The preference is for the more substituted carbon atom to end up at the 5-position of the heterocyclic product (153,154). However, cases of opposite regiodifferentiation are also found, in particular with donor-substituted alkenes (42,155-157) (Scheme 6.21). 

The many successful applications of nitrile oxide cycloadditions in synthesis are intimately linked with theory, both the simple FMO variety as well as the more sophisticated ab initio treatment, where the work of Sustmann and subsequently of Houk and his group has been seminal. We, the practitioners, have thus been supplied with a consistent view on the nature of 1,3-dipoles, their reactivity toward dipolarophiles, and the origin and interpretation of stereoselectivity of cycloaddition chemistry. It is of course desirable that our understanding of the relative reactivities of alkenes as well as of many 1,3-dipoles would be also improved, thereby leading to simple, extended recipes for the chemist practicing synthetics. We hope that this account will stimulate further advances in this field of cycloaddition chemistry and promote further uses of nitrile oxides in organic synthesis. 

Complexes were also considered for other carbenes and even suggested for reactions in alkane solution( ) A counterproposal, backed by the inability of theory to find support for such stable complexes, held that the second source was not the carbene-alkene complex but instead was the diazo compound, formed from isomerization of excited diazirine. " Other LFP studies reinforced the need for two intermediates, but could not finally resolve the question of carbene complexes ver-sus diazo compound. However, the question is now settled in this case,... 

Use orbital interaction theory to develop the orbitals of the 2-oxaallyl system, R2C— —CR2, also known as a carbonyl ylide. Show why 2-oxaallyl readily reacts with alkenes and alkyne in a 4 + 2 cycloaddition reaction (an example may be found in El-Saidi, M. Kassam, K. Pole, D. L. Tadey, T. Warkentin, J., J. Am. Chem. Soc., 1992, 114, 8751-8752). 

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