Regioselectivity secondary orbital interactions

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

Secondary orbital interactions may also be involved in controlling the regioselectivity, if the differences between the terminal coefficients of diene and dienophile are small61. 

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... 

Secondary orbital interactions have also been invoked to explain regiochemistry as well as stereochemistry. Whereas 1 -substituted dienes sometimes have only a small difference between the coefficients on C-l and C-4 in the HOMO, they can have a relatively large difference between the coefficients on C-2 and C-3. Noticing this pattern, Alston suggested that the regioselectivity in Diels-Alder reactions may be better attributed, not to the primary interactions of the frontier orbitals on C-l and C-4 that we have been using so far, but to a... 

Examination of such interactions is important for the understanding of regioselectivity in Diels-Alder reactions. Houk formulated a general approach for secondary orbital interactions. ... 

Secondary orbital interactions of alkenes bearing substituents having a n-bond lead to a preference for the endo product in the Diels-Alder reaction. This reaction is regioselective due to interactions of orbital coefficients on the orbitals of the reacting atoms. Substituents at Cl and C4 of the diene move in a disrota-tory manner and opposite, relative to the incoming alkene. 

In addition to regioselectivity and transition state demands, one has to be aware of the endo-preference of Diels-Alder reactions, which is ascribed to secondary orbital interactions in the transition state. 

The reactivity, regioselectivity and stereoselectivity of [3+2] cycloadditions of oxazoline 7V-oxides and a,P-unsaturated esters or nitroalkenes can be rationalized in terms of the FMO theory. The reactions are HOMO-dipole controlled and the preferred ewi/o-selectivity in those cycloadditions can be rationalized by stabilizing secondary orbital interactions only present in the en[Pg.105]

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