The explanation in mine textbook states that the endo product allows for much more interaction in between the diene and also dienophile during the shift state.
I also found the following post, which argues that an additional orbital interactions are the cause. Stereoivorycrimestory.com of product in Diels-Alder reaction
Then I uncovered the following record that indicates, at the very least to my understanding, the steric strain throughout the transition state is the key reason behind the endo dominion (or at the very least for the example reaction in the article). Https://www.ncbi.nlm.nih.gov/pubmed/24449044
So, I"m left wondering what is the reason for the endo rule?
organic-ivorycrimestory.com molecular-orbital-theory pericyclic stereoselectivity
boost this concern
edited Oct 13 "17 in ~ 22:08
61.3k1010 gold badges204204 silver- badges353353 bronze title
request Dec 10 "16 in ~ 3:25
55955 silver- badges1313 bronze title
include a comment |
2 answers 2
energetic earliest Votes
What is the endo-selectivity the Diels-Alder reactions?If the diene supplied in the Diels-Alder reaction has asymmetric substituents in ~ the finish carbons, and also if the dienophile is unsymmetric, then two different isomers of the final adduct have the right to form. The isomer, wherein the sensible group(s) (usually carbonyl) ~ above the alkene finish up ~ above the very same side together the recently formed twin bond, is referred to as the endo-isomer <1>. The various other one is the exo isomer. The naming of the isomers deserve to be a little ambiguous in instances where there space multiple functional teams of different varieties on the starting alkene. Typically the electron-withdrawing team is thought about when identify which isomer is endo and also which is exo.
You are watching: Why is endo product favored in diels alder
The experiment tell united state that, in general, the endo-product is the one i m sorry is favoured kinetically i.e. It forms faster. This is not a rule as such, due to the fact that there is no means to predict come what degree the endo product will be favoured. (In plenty of cases, the exo product is the thermodynamic product i.e. Much more stable, so permitting the reaction come equilibriate will result in higher yield that exo product)
Why does this happen?
It"s complicated to answer this inquiry definitively, due to the fact that there is quiet a lot of of active research walking on in the area. Ns will try to summarise the main impacts which have actually been suggest as feasible causes of the endo-selectivity.Secondary orbital interaction
The interaction between the frontier molecule orbitals in ~ the points wherein the brand-new $\sigma$-bonds kind are the first-order interactions. However, over there are various other interactions feasible between the diene and dienophile, there are referred to as second-order interactions, or second orbital interactions (SOI). This explanation was proposed through Woodward and also Hoffmann, in the book The conservation of orbit symmetry<3>.
The complying with diagram will certainly be useful:
As you have the right to see, in the shift state bring about the endo-product, the carbonyl part of the alkene can communicate with the earlier of the diene, and the communication is favourable, together the symmetry matches. In the transition state leading to the exo-product, this communication would not be available, as the carbonyl group is away from the diene. For a long time, SOI was thought about as the right answer, and was generally invoked in explaining not simply Diels-Alder reaction, however other species of cycloaddition reactions together well.
However, there are a lot of evidences, both experimental and computational, i beg your pardon calls into question the validity that SOI. There is a good record from Salvatella et.al. Summarising them: "Do second Orbital Interactions yes, really Exist?" Acc. Chem. Res., 2000, 33, 658.
For example, the dimerization that butadiene was presented to have actually slight endo preference.
This was commonly used as an instance of the SOI effect. However, computational researches at RHF and CASSCF level have found that the reaction proceeds via a stepwise mechanism. <6> If the device is stepwise, not concerted, climate it does no go through the constrained change state which is required for the an additional orbital interactions to come into existence. So, we cannot invoke SOI because that this endo-preference.Steric effects
In specific Diels-Alder reactions, specifically those entailing the cyclopentadiene, steric effects have to be proposed.
Experimental data mirrors that once $\ceR$ = $\ceCH3$ and $\ceX$ = $\ceCHO$ the endo product is developed in $17.0%$ yield, i.e. The exo product currently dominates. <7> This shows that the steric repulsion that cyclopentadiene ring through $\ceCH3$ and the is better than that with $\ceCHO$, i beg your pardon is regular with $\ceCH3$ being bulkier.
These monitorings can also be described by SOI, yet the trends in the endo-selectivity for a variety of $\ceR$ and also $\ceX$ teams seem come fit better to the steric argument.<5>
In a much more recent research by Fernandez and Bickelhaupt, the selectivity was found to arise from activation strain, i.e. Steric strain as the reactants strategy the transition state.<12> They supplied $\mathrmM05\text -2X/def2\text -TZVPP$ to model the reaction the cyclopentadiene and maleic anhydride.
The above image, take away from your paper, shows the full reaction coordinate, with ZPE-corrected energies in kcal/mol and distances in Å. Together you can see, the exo-reactant complex (exo-RC) is greater in energy than the endo one, saying that the strain comes right into existence even before the TS. The extra strain in the exo-pathway is thought to arise from the steric repulsion in between the methylene the cyclopentadiene and the oxygen of the anhydride.Hydrogen bonds
Hydrogen bond-like interactions between C-H in alkene and also the twin bond has also been proposed together a cause of endo-selectivity in specific cases, such together the reaction that cyclopropene and butadiene.<8> Here, both steric effects and also H-bond prefer interactions room thought to be present.
This is somewhat various than the SOI interaction, due to the fact that in SOI, only orbital overlap (delocalization) is considered. H-bond interactions are a amount of orbit overlap and also electrostatic attraction.Electrostatic forces
Electrostatic pressures can be offered to define the inexplicable exo-selectivity the the furan+cyclopropenone addition.
In the exo-TS, over there is a favourable electrostatic interaction in between the electronegative O that furan and the electropositive carbonyl carbon that cyclopropenone. This provides the exo-isomer the wanted one. The exo-TS is around 1.81 kcal/mol reduced in power than the endo-TS, according to computational studies. <9>
The usual endo-selectivity of various other Diels-Alder reaction can also be defined by the electrostatic repulsion between slightly electropositive terminal C-H the the diene, and the electropositive carbon that the electron-withdrawing team on dienophile:
Sustmann and also others lugged out computational research studies on Diels-Alder reactions in both gas phase and with dielectric-continuum solvation.<10> They found that in the gas phase, the exo-TS is lower in power i.e. Kinetically favoured. Using a solvation model caused the endo-TS being the favoured one.
They suggested that solvent effect can be the cause of endo-selectivity. The endo-TS is generally an ext polar than the exo-TS, so the is stabilised come a greater extent in solvent. It is also observed the the choice for endo-TS boosts the more polar the solvent is, i beg your pardon lends assistance to this argument. The gas phase exo-preference would additionally disprove the function of SOI effects, since they need to be present regardless of solvation.
However, computational studies favor these need to be thought about carefully, since they were mostly brought out making use of HF or B3LYP methods, both of i beg your pardon severely underestimate dispersion pressures (which are important to describe SOI). So, the results might be artificially it was crooked in the direction the exo-TS. <11>
All that this method that we are not really sure if there is a single cause the can define the endo-selectivity in Diels-Alder reactions.
In considerable experimental-computational examine , Paddon-Row et. Al.(2020) learned reactions of isotope labelled butadienes through mono- or di-substituted alkenes.<11> Surprisingly, it was uncovered that mono-substituted alkenes (such as methyl acrylate) walk not have actually a solid endo-preference as soon as the reaction was done in benzene solution. Methyl acrylate and also butadiene, for instance gave 50:50 exo-endo product yield. Di-substituted alkenes showed greater endo-selectivity. In their analysis they argued that SOI effects are important in part cases, vice versa, steric impacts are forcing the selectivity in some various other cases.
So, it could just be that various effects are working in different reactions, and somehow the end an outcome is the endo-product is favoured in nearly all cases. Climate it can not be advantageous to look because that one details blanket reason of the selectivity, rather, each reaction has to be explained uniquely.
(1) Organic ivorycrimestory.com, Clayden, Greeves, Warren, 2nd ed., Oxford college Press, p.884
(2) image source: https://employees.csbsju.edu/cschaller/Reactivity/pericyclic/peri%20endo.htm
(3) The preservation of orbital symmetry, R B Woodward, R Hoffmann, Weinheim : Verlag Chemie GmbH, 1971
(4) picture source: https://www.cpp.edu/~psbeauchamp/pdf/316_MO_DA_rxn.pdf
(5) picture source: Acc. Chem. Res., 2000, 33, 658
(6) Y. Li and K. N. Houk, J. Am. Chem. Soc., 1996, 118(4), 880–885
(7) Y. Kobuke, T. Fueno, J. Furukawa, J. Am. Chem. Soc., 1970, 92, 6548-6553
(8) M. Sodupe,R. Rios,V. Branchadell, J. Am. Chem. Soc., 1997, 119, 4232-4238
(9) S. M. Bachrach, J. Org. Chem., 1995, 60, 4395-4398
(10) T. Karcher, W. Sicking, J. Sauer and also R. Sustmann, Tetrahedron Lett., 1992, 33, 8027–8030
(11) W. J. Lording, T. Fallon, M. S. Sherburn, M. N. Paddon-Row, Chem. Sci.
See more: City Of Fullerton Business License Online Renewal, Starting A Business
, 2020, 11, 11915–11926
(12) I. Fernández, F. M. Bickelhaupt, J. Comput. Chem., 2014, 35, 371– 376. DOI: 10.1002/jcc.23500