Regioselectivity in Diels*Alder Reactions

Intramolecular Diels-Alder reactions may give the endo product or they may not Be prepared for either exo or endo products or a mixture. 

The compounds that we are now calling dienophiles were the stars of Chapters 10, 23, and 29 where we called them Michael acceptors as they were the electrophilic partners in conjugate addition reactions. Nucleophiles always add to the (3 carbon atoms of these alkenes because the product is then a stable enolate. Ordinary alkenes do not react with nucleophiles. 

In frontier orbital terms this is because conjugation with a carbonyl group lowers the energy of the LUMO (the 71 orbital of the alkene) and at the same time distorts it so that the coefficient on the 

P carbon atom is larger than that on the a carbon atom. Nucleophiles approach the conjugated alkene along the axis of the large p orbital of the (3 carbon atom. 

These same features can ensure regioselective Diels-Alder reactions. The same orbital of the dienophile is used and, if the HOMO of the diene is also unsymmetrical, the regioselectivity of the reaction will be controlled by the two largest coefficients bonding together. 

So what about distortion of the HOMO in the diene If a diene reacts with an electrophile, the largest coefficient in the HOMO will direct the reaction. Consider the attack of Hbr on a diene. We should expect attack at the ends of the diene because that gives the most stable possible cation—an allyl cation as an intermediate. 

In orbital terms attack occurs at the ends of the diene because the coefficients in the HOMO are larger there. We need simply to look at the HOMO ( 2) of butadiene to see this. 

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Two proofs for the HSAB principle were provided under the restriction of a common chemical potential of the reaction partners [83, 84]. Later on, a local HSAB principle was provided by Gazqu z and Mendez [85], They showed that the interaction between two chemical species will not necessarily occur through their softest atoms, but through those whose softnesses are approximately equal. In Section 4.2, an intuitive application of the HSAB concept is provided, followed by an application of the local HSAB principle in the interpretation of regioselectivity in Diels Alder reactions. 

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... 

Table 4-2 Regioselectivity in Diels-Alder reactions predicted by considering only the frontier orbital contributions...

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

Interactive explanation of regioselectivity in Diels-Alder reactions... 

Regioselectivity in Diels-Alder reactions 889 Radicals form by homolysis of weak bonds 971... 

Bansal RK, Karaghiosoff K, Gupta N, Gandhi N, Kumawata SK (2005) Diasteieo- and regioselectivity in Diels-Alder reaction of [1,4,2] diazaphospholo[4,5-a]pyridines. Tetrahedron 61 10521-10528... 

SCHEME 4.16 Regioselectivity in Diels—Alder reaction continued. 

Casetta, M. Colona, S. Manfredi, A., Hydrophobic control of organic stereochemistry. Changes of regioselectivity in Diels-Alder reactions by salt effects, Gazz. Chim. Ital, 1989, 119,533-5. 

Regioselectivity in Diels-Alder Reaction Regioselectivity during Diels-Alder reaction is based upon the rule that major product from Diels-Alder reaction will arise from transition state that resemble the most stable of the possible diradical intermediates that might be formed in the reaction. An... 

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