13.4: Diels-Alder Regio- and Stereoselectivity

Last updated
Save as PDF

Page ID: 366321

\( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \) \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)\(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\) \(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\)\(\newcommand{\AA}{\unicode[.8,0]{x212B}}\)

Despite all of this, it still might not be obvious why we observe the regioselectivity and stereoselectivity we do. In general, Diels-Alder reactions proceed so that an atom with the largest coefficient in the HOMO will pair with the atom with the largest coefficient in the LUMO. Take, for example, the example above. Because of resonance, the dienophile would have electron density concentrated on the terminal carbon. In the diene, the largest coefficient will also reflect important resonance structures. Since we are talking about a LUMO, we are looking for a position that has partial positive charge.

Screen Shot 2022-12-29 at 10.06.53 AM.png

So, when you are trying to determine regioselectivity, line up the most reactive atoms:

Screen Shot 2022-12-29 at 10.07.03 AM.png

What about stereoselectivity? In general, Diels-Alder reactions can give two products: endo and exo, which form based on the approach of the dienophile to the diene. The endo product is normally favored.

Screen Shot 2022-12-29 at 10.07.14 AM.png

What explains the endo selectivity? Again, we must consult molecular orbital theory. Consider the following normal Diels-Alder reaction, where the Frontier molecular orbitals (HOMO_diene-LUMO_dienophile) are drawn:

Screen Shot 2022-12-29 at 10.07.22 AM.png

In the transition state, there is an extra bonding interaction with the carbonyl and the C₃ carbon of the diene. This interaction does not happen in the exo transition state since it is pointed in the opposite direction. This addition bonding interaction is called secondary orbital overlap, and requires the presence of a \(π\) system to overcome the steric strain of the endo transition state.

How can we predict the stereoselectivity? By drawing the transition states!

Screen Shot 2022-12-29 at 10.07.36 AM.png

Here’s an example that combines prediction of both regioselectivity and stereoselectivity:

Screen Shot 2022-12-29 at 10.07.47 AM.png

And, finally, one last example:

Screen Shot 2022-12-29 at 10.07.58 AM.png

This time, the exo product is favored because there is no possibility for secondary orbital overlap. Steric considerations dominate the transition state, so exo is formed. Notice also that the Diels-Alder reaction is stereospecific – the stereochemistry of the dienophile is retained in the product because the cycloaddition is a concerted process.