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Dienes and MO Theory

By James Ashenhurst

Exo vs Endo Products In The Diels Alder: How To Tell Them Apart

Last updated: October 25th, 2022 |

Today we’ll cover how to tell endo– and exo- products apart in the Diels-Alder reaction. Shortcut below.  For the long-winded walkthrough with lots of examples, read more below.

quick rule for telling endo and exo diels alder reaction products apart endo product has outside group of diene on same face of new ring as ewg on dienophile

Table of Contents

  1. Exo and Endo Products In The Diels-Alder
  2. Exo And Endo Diels-Alder Products Are Diastereomers Of Each Other
  3. 3-D Models Of The Endo And Exo Products In The Diels-Alder Between Cyclopentadiene And Maleic Anhydride
  4. Distinguishing ”Endo” vs “Exo”: Pay Attention To The Relationship Between The “Outside” Groups On The Diene And The EWG On The Dienophile
  5. Another Worked Example: Cyclopentadiene And Quinone
  6. How Do You Know If A Diels-Alder Will Give You Endo And Exo Products?
  7. Four More Examples (Including A Trick Question)
  8. Transition States In A Diels-Alder That Does NOT Lead To Endo And Exo Products
  9. Transition States In A Diels-Alder That Leads To Exo and Endo Products
  10. So Why Is The Endo Product Favored?
  11. Notes

1. Exo and Endo Products in the Diels-Alder

In this series of articles on the Diels-Alder reaction, we’ve seen that:

  1. the Diels-Alder reaction always involves the breakage of 3 pi bonds and the formation of 3 new bonds (2 sigma, one pi), resulting in the formation of a new six-membered ring. [Intro]
  2. The stereochemistry of the dienophile is preserved. A cis arrangement of groups in a double bond will result in a cis arrangement in the new six-membered ring. And likewise,  trans →  trans
  3. For dienes, the two “outside” groups on the diene each end up on the same face of the new six-membered ring. Likewise, the two “inside” groups each also end up on the same face of the new ring.

(These last two parts are from the last post, where we went through the stereochemistry of the Diels-Alder reaction.)

Now let’s add the next layer of detail.  For certain diene/dienophile combinations,  we can end up with two products that fulfill all of those criteria. For instance:

a diels alder reaction that gives two diastereomers cyclopentadiene and quinone two stereoisomers that are diastereomers 4 to 1 ratio these are called endo and exo

2. Exo And Endo Diels-Alder Products Are Diastereomers Of Each Other

These two products are stereoisomers. But since they are not non-superimposable mirror images (i.e. not enantiomers), they are diastereomers. hover here to view a pop-up image [In fact, each of these molecules are achiral, due to the presence of a mirror plane – if you can’t see it, click here ] 

These two molecules can be separated due to the fact that they have different physical properties.

An as it turns out, the major product is the one above left. The minor is the one above right.

Sometimes it can help to look at these things in perspective:

diels alder products exo and endo top view and side view perspective

3. 3-D Models Of The Endo And Exo Products In The Diels-Alder Between Cyclopentadiene And Maleic Anhydride

Here are the two products again (major and minor) built as models.

  • on one product (bottom left), the dienophile is on the underside (“concave”) face of the ring, pointing “in” toward the alkene
  • on the other product, the dienophile is on the convex face of the ring, pointing “out”, away from the alkene.

using models to show difference between endo and exo where endo is more cup shaped and exo is less

When Diels and Alder originally discovered this phenomenon, they assigned the name “endo” to the major product (where the dienophile is pointing “in”, towards the alkene) , and the term “exo” (outside, such as in “exoskeleton”) to refer to the minor product (where the dienophile is pointing “out”, away from the alkene).

In this particular example, identifying “exo” and “endo” seems straightforward based more on an appeal to intuition than anything else. But trust me when I say that there are plenty of examples where it isn’t so easy to assign.

4. How To Recognize The “Endo” And “Exo” Products In A Diels-Alder Reaction: Pay Attention To The Relationship Between The “Outside” Groups On The Diene And The EWG On The Dienophile

In that vein, it’s helpful to have a standard “rule” that we can apply to each situation.

Here’s one way to do it:

Think of the endo as being the diastereomer where the “outside” group on the diene is on the same side of the new six-membered ring as the “electron-withdrawing group” on the dienophile.

The exo is the diastereomer where the outside group on the diene is on the opposite side of the new six-membered ring as the electron-withdrawing group on the dienophile. 

quick way to discern endo and exo is to examine outside groups on diene with ewg on dienophile and if outside groups are on same side of ring that is the endo

5. Another Worked Example: Cyclopentadiene And Quinone

Let’s try applying those rules to the products of the first reaction we looked at. In the endo drawn below, the “outside” group on the diene (the hydrogens) points down, and the bond to the carbonyls on the dienophile point down as well. Same side of the new ring.

In the exo the outside group (hydrogen) is down and the bond to the electron-withdrawing group points up. Opposite sides of the new ring.

specific example of endo and exo is cyclopentadiene with quinone giving endo product example and exo product example
6. How Do You Know If A Diels-Alder Will Give You Endo And Exo Products?

So how do you know if a given Diels-Alder is going to have endo and exo products?

Here’s a short answer. (A longer, more comprehensive answer follows at the bottom of the post). 

  • If all of the “outside” groups on the diene are the same as the “inside” groups, then there can’t be exo or endo. Butadiene itself, for example; the “inside” and “outside” groups are both hydrogens.
  • If the dienophile lacks a substituent that can be distinguished as the “electron withdrawing group”, then there won’t be exo or endo. Ethylene is a clear example, as is tetracyanoethylene. Or acetylene and derivatives like DMAD.  [Note 1] There are also a few interesting dienophiles [example 4] where exo– and endo- products are not possible for a more subtle reason.

7. Four More Examples (Including A Trick Question)

Let’s look at a few more examples.

Example 1: 2,4-hexadiene (diene) and acrolein (dienophile)

Note that the endo product has the methyl groups on the same face of the ring as the aldehyde (both dashes, as pictured, or both wedges, as in the enantiomer). The exo product has the methyl groups on the opposite face of the ring as the aldehyde.

Example 2: Cyclopentadiene and maleic anhydride

example of exo and endo products in diels alder reaction cyclopentadiene with maleic anhydride endo and exo no enantiomers meso example clearly why endo and exo
This is very similar to the original example, where the endo has the anhydride ring on the concave face, and the exo has the anhydride on the convex face.

Example 3: Cyclohexadiene and methacrylonitrile

example 3 of exo and endo diels alder showgs cyclohexadiene with methacrylonitrile endo and exo clear example

Here, the nitrile is clearly the electron withdrawing group, and so it’s the functional group we judge endo and exo by, rather than the methyl group. I should note that when you look at a model of the product, the hydrogen is not really pointing “down” (it points out, more than anything else) but it’s certainly “down”, relative to the inside group (the CH2CH2 bridge).

Example 4.  Here’s a fun one: Cyclopentadiene and dimethyl fumarate

exo and endo diels alder reaction examples with cyclopentadiene and dimethyl fumarate no endo or exo in this case why

Our dienophile has two electron withdrawing groups placed on opposite sides of the pi bond. So which electron withdrawing group do we point to when determining exo or endo ?

We can’t distinguish them! Therefore there is no exo or endo in this case. The product will, however, exist as a mixture of enantiomers. [Note 2] . And yes, these two molecules are enantiomers, not diastereomers. Hover here for a pop-up view  or click this link.

8. Transition States In A Diels-Alder That Does NOT Lead To Endo And Exo Products

This post is just intended to give some examples of discerning exo and endo, and we can leave it at that.

It’s worth one last look, however, at how exo and endo might arise.

First,  let’s imagine how cyclopentadiene might come together with ethene in a Diels-Alder.

Cyclopentadiene can approach “head-first” (where C-7 floats over ethylene first) or “butt-first” (where C2-C3– floats over ethylene first). But because both sides of ethene are exactly the same, each of these approaches lead to the same product.

There is no possibility of  exo and endo here.

transition state of diels alder reaction cyclopentadiene with ethene no matter what direction cyclopentadiene approaches same product results

9. Transition States In A Diels-Alder That Leads To Exo and Endo Products

Now, let’s look at how cyclopentadiene can approach a substituted dienophile like maleic anhydride.

Maleic anhydride does have a “head” and a “tail”, unlike ethylene. The two approaches of cyclopentadiene to maleic anhydride are therefore not equivalent, which results in two different transition states (diastereomeric transition states) which leads to two different products. [Note 3]

This is the origin of endo and exo!

transition state of diels alder reaction with cyclopentadiene and maleic anhydride shows how the groups point in opposite directions in the endo and in the same direction in the exo

10. So Why Is The Endo Product Favored?

But, you might ask, why is it that the endo product is favored over the exo by so much – especially when it seems like the endo product has much more steric hindrance than the exo?

That is a great question. Let’s look at it next time.

[Next post: Why Are Endo Products Favored In The Diels-Alder? ]

Notes

Related Articles

Note 1. In a pinch, CH3 or other groups that are not technically “electron withdrawing groups” can serve as placeholders for our exo-endo shortcut.

how do you assign exo and endo when the electron withdrawing gruop on the dienophile is actually an alkyl group it is the same process endo and exo assigned
This frequently comes up in inverse electron-demand Diels-Alder reactions, where the “dienophile” is electron rich and the diene electron-poor.

Note 2. Dimethyl fumarate has a property called “C2-symmetry” , which is the property that turning it 180° in one direction leads to an indistinguishable molecule. (The letter “S” has that property).

Note 3. Things get even more complicated when either the diene or dienophile is non-symmetrical; this results in 4 possible products; two enantiomeric endo transition states, and two enantiomeric exo transition states.

00 General Chemistry Review
01 Bonding, Structure, and Resonance
02 Acid Base Reactions
03 Alkanes and Nomenclature
04 Conformations and Cycloalkanes
05 A Primer On Organic Reactions
06 Free Radical Reactions
07 Stereochemistry and Chirality
08 Substitution Reactions
09 Elimination Reactions
10 Rearrangements
11 SN1/SN2/E1/E2 Decision
12 Alkene Reactions
13 Alkyne Reactions
14 Alcohols, Epoxides and Ethers
15 Organometallics
16 Spectroscopy
17 Dienes and MO Theory
18 Aromaticity
19 Reactions of Aromatic Molecules
20 Aldehydes and Ketones
21 Carboxylic Acid Derivatives
22 Enols and Enolates
23 Amines
24 Carbohydrates
25 Fun and Miscellaneous

Comments

Comment section

33 thoughts on “Exo vs Endo Products In The Diels Alder: How To Tell Them Apart”

  1. Really its a nice post & have great topic discussion .
    its a concept booster…..
    thankyou so much!
    actually my query regarding this topic is that:

    when cis,cis-3,4-dimethylcylobutene is subject to reaction photochemically dis-rotation ring opening, what will be the product?
    either cis or trans ?

    Reply

    1. There’s been some previous discussion on this thread regarding IUPAC and their use of exo/endo versus how the terms are actually used in practice. My general opinion on this one is that IUPAC can get stuffed because nobody follows their recommendations on this topic.
      If there is a specific image that is causing confusion to you, could you specify which one (image filenames are numbered, so that would help).

      Reply

  4. How do we depict formation of endo and exo products in cycloaddition reactions involving 1,3-dipolarophile such as a nitrone and a dipolariphile such as an activated olefin. Thanks

    Reply

  6. you are right. it was my fault for relying on ChemDraw to name these. should have relied on the old school do-it-by-hand.

    Reply

  7. these are the iupac names for the two “enantiomers” in example 4:
    dimethyl (1R,2R,3R,4S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate
    dimethyl (1R,2R,3S,4S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate

    they are not enantiomers otherwise the 2nd molecule would be dimethyl (1S,2S,3S,4R)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate

    Reply

    1. If we started with dimethyl(1R, 2R, 3R, 4S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate and did a single swap (i.e. flipped) all four stereocenters, you would get the enantiomer. Agree?
      If so, then would you agree that the name of that enantiomer would be (1S, 2S,3S,4R)bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate?
      As it turns out this is not correct (!!) due to a quirk of IUPAC nomenclature (priority of numbering). A picture says more than a lot of words would. Here is a link to an explanation I made. https://www.masterorganicchemistry.com/wp-content/uploads/2020/02/Supp-More-Iupac-exo-endo.gif

      Here is a screenshot of the IUPAC rule from the Blue book: https://www.masterorganicchemistry.com/wp-content/uploads/2020/02/Supp-priority-of-R-over-S-1.png

      Reply

  10. NOTE. Updated April 15, 2019. The top image was modified so that it is consistent with the other images in the post (i.e. “outside” groups turning into dashes). The previous version had them turning into wedges which was confusing for some students. Thank you to Daniel A. for the correction.

    Reply

  11. “endo product has much more steric hindrance than the exo”
    Is there any paper in rather high quality journal with this statement? I have no doubt on ut but my chief asking for pubs to cite such statenent in our manuscript. And I can’t just wrute that it is obvious.

    Reply

  13. Would have been nice to know all this before I wasted my limited time learning something that won’t be on my crucial entrance exam since it never includes anything controversial or in contradiction of IUPAC. Same thing all over the internet, so I wouldn’t have known if I hadn’t read this comments section.

    Reply

  14. I am thinking probably that the “out group” trick would predict the correct product for your reaction, but the proper application of IUPAC nomenclature would designate it an exo product? Secondary orbital overlap I think suggests the correct product.

    My point still stands: if a formal definition, (like you’ve described from the IUPAC gold book) arbitrarily detracts from our understanding of the chemistry, then maybe it is time to reconsider the definition, or at least loosen it in certain contexts. I think the IUPAC books are updated very infrequently.

    But don’t take my word for it, I think many chemists have already come to that conclusion. For example, a recent chemical review product where a monocyclic product is referred to as an exo product: https://pubs.acs.org/doi/abs/10.1021/cr078346g

    Regardless, it’s interesting to learn about this quirky nomenclature fact!

    Reply

    1. According to the strict IUPAC rules, it will be anti, exo/endo are not applicable in this case as the group is on the highest numbered bridge. It’s a mess, I know. Yet, by being the devil’s advocate, I got everyone to scratch their heads more than once and made James write a lengthy and excellently elaborated comment on the topic :D

      Reply

      1. Would have been nice to know all this before I wasted my limited time learning something that won’t be on my crucial entrance exam since it never includes anything controversial or in contradiction of IUPAC. Same thing all over the internet, so I wouldn’t have known if I hadn’t read this comments section.

        Reply

  15. If endo/exo is technically incorrect for referring to monocyclic products, then how else should the two diastereomeric products be described?

    Regardless of whether the product is a bicycle, the chemical reason for the observed product is the same: there is some attraction (its true sourced debated I think) between the group on the dienophile and the underside of the pi system in the diene. Given that fact, it seems this is a case where “official” nomenclature does a poor job of doing chemistry justice.

    I looked through 3 textbooks (Wade, Bruice, Loudon) and 2/3 of the textbooks limit their discussion of endo/exo rule to bicycles. Loudon describes it similarly to what is in this blog post.

    I also know that at most of the better schools I’ve tutored students at, the professor will describe the endo product in the same way as described in this blog post: in the endo product, the “out” groups on the diene are cis with the withdrawing group on the dienophile. This is also how I recall learning it in graduate school.

    Reply

    1. Using endo/exo for monocyclic compounds is as correct as using cis/trans for the two diastereomers of 3-methyl-3-heptene.

      Nobody argues about the nature of the product, btw ;) Only how we call it and describe the process. Thus, there are better interpretations of the rule, still using the bridges.

      Yes, Loudon p 740 does describe exo/endo same way as this post. Still doesn’t make it correct as the IUPAC is the final authority for the nomenclature.

      There’s a lot of poor explanations and incoherent statements across the chemical education. So, as educators, we must hold ourselves to the high standard and acknowledge when we are presenting a trick or a shortcut as opposed to the official rule. Explaining exo/edo via the bridge is the interpretation of the actual rule, explaining it via the relative position of the out-groups and EWG is a shortcut or heuristics if you like. We also must acknowledged when we’re using the official language of chemistry and the “common-talk” when we explain things.

      PS: so, what’s the descriptor for the reaction I proposed earlier?

      Reply

  16. khm…
    IUPAC rule P-93.5.2.2.1 The stereodescriptors ‘endo’, ‘exo’, ‘syn’, and ‘anti’
    I quote: “if the substituent is oriented TOWARDS THE HIGHEST NUMBERED BRIDGE it is given the description ‘exo’; if it is oriented away from the highest numbered bridge it is given the description ‘endo’. If the substituent is attached to the highest numbered bridge and is oriented towards the lowest numbered bridge it is given description ‘syn’; if the substituent is oriented away from the lowest numbered bridge it is given the description ‘anti’.
    So, while your explanation of ‘exo’ and ‘endo’ work here, they are, strictly speaking, incorrect.

    Reply

    1. Hi Victor – thank you for noting the IUPAC rule, which was an important omission. Given that, can you come up with a reasonable example in the context of an introductory course where the rule-of-thumb rule I proposed doesn’t work? For many of the students I’ve tutored, applying the IUPAC rule as written is not something they are likely to do or to remember….

      Reply

      1. 2H-pyran + maleic anhydride ;)

        And I’m all for quick rules that make student’s life easier. However, I like to make sure that it is noted that “this is a trick” rather than the actual rule. Students might (and do) misread. Same thing like I occasionally see the lowest sum of numbers “rule” for numbering a chain which works almost always. With the big emphasis on ‘almost’.

        The IUPAC rules are sometimes written in an awkward way, so I agree that they might not be very useful in the “raw” form. Yet, many textbooks also refer to the bridge when explaining the endo/exo, so that’s the big discrepancy here with how books/instructors approach and test it, and how you explain it. Randomly grab Solomons 11th ed from my shelf: p 613.

        Finally, using endo/exo for monocyclic products is inappropriate. IUPAC only talks about the endo/exo-like approach, but the actual terms ‘endo’ and ‘exo’ are reserved for the bicyclic structures with combined length of 7 or less atoms between the bridges.

        Reply

    2. Here’s my view on this.
      Short view is: Yes, it’s against IUPAC. Yes, it deserves a note that it does so. But only in a few select cases (below) does it create conflict. Given the tremendous utility of the Diels-Alder, the exo- and endo- descriptors above are omnipresent in non-bicyclic cases in prominent, high-impact journal articles used by all in the synthetic organic community. Journal editors + authors aren’t enforcing the IUPAC standard. Why should I? The article (and site) is meant to be utilitarian. I would rather have someone understand the terms as they are used in the field, rather than puzzle through the IUPAC definition and not obtain an answer. Like the Oxford English Dictionary, IUPAC is a lagging indicator of usage, and is mutable.
      [Longer argument]
      1. In the context of, say, epoxidation of norbornene or other systems, the IUPAC rules are useful and clear on identifying an exo or an endo face. For example, with the epoxidation products below, it’s clear and unambiguous which products are exo and endo.
      exo-endo-1
      2. Due to the popularity of the Diels-Alder reaction, the usage of the terms exo and endo has expanded far beyond this use-case. March (to take one example) and other canonical textbooks are careful to use (italicized) exo and endo to refer strictly to examples where the exo and endo products conform to the IUPAC designation. But when talking about the diastereomeric transition states for the self-reaction of butadiene, even March can’t avoid mentioning exo and endo transition states (even if it’s not italicized) for an example leading to a substituted cyclohexene ring. (I’m using 5th ed).
      3. In most situations, endo products tend to dominate. Secondary orbital effects are often cited as the cause. An exo- selective Diels-Alder reaction is a rare thing, generally due to additional steric effects (e.g. 2-chloroacrylonitrile with cyclopentadiene).
      4. However, according to IUPAC, the Diels-Alder of cycloheptadiene with (say) acrolein would lead to a product that in every respect follows the same stereoelectronic effects mentioned previously (“endo” selectivity) but because of what I would consider to be a quirk of IUPAC nomenclature, is officially called “Exo”:
      exo-endo-3
      5. So clearly there’s a conflict. Which to use? I would argue to screw IUPAC, which is not holy writ, and to still employ the endo and exo in the sense for smaller ring sizes. This avoids any disambiguation in describing the reaction of maleic anhydride with cycloheptadiene with maleic anhyrdide as “exo-selective” when it follows the exact same stereoelectronic course as, say, its reaction with cyclopentadiene.

      IUPAC can retire the previous definition.

      Reply

  17. Great post.
    Two small corrections suggested:
    – in Example 1, that is not butadiene, but 2,4-hexadiene;
    – in Example 3, that is not acrylonitrile, but methacrylonitrile (2-methylacrylonitrile).

    Reply

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