Conformations and Cycloalkanes
Naming Bicyclic Compounds – Fused, Bridged, and Spiro
Last updated: August 12th, 2020 |
Bicyclic Compounds – Fused Rings, Bridged Bicyclic Rings, and Spiro Bicyclic Rings
In the previous post we started our discussion of structures with more than one ring, using decalin as our key example of a fused ring. We saw how much the stereochemistry at the ring junction can affect the overall shape of the molecule, as well as its stability.
Table of Contents
- Ring Junctions: Fused Rings, Bridged Bicyclic Rings, and Spiro Rings
- In Or Out? Either Both In, Or Both Out!
- Putting Bridged Bicyclic Compounds In Perspective
- Naming Bridged Bicyclic Compounds – A Five-Step Guide
- A Few More Examples Of Bridged Bicyclic Molecules
- Naming Spiro Compounds
- Summary: Naming Bicyclic Compounds
- Notes (and a complex example)
- (Advanced) References and Further Reading
What we didn’t talk about is that the ring junction of decalin represents only one way to arrange the ten carbons of decalin into a pair of adjacent rings: the so-called “fused” ring structure, where the two “bridgehead” carbons are directly connected. There are actually two other modes of ring junction. In “bridged bicyclic” molecules, the two bridgeheads are separated by “bridges” containing at least one carbon. In “spiro” fused molecules, the two rings are both joined at the same carbon.
In this post we’ll focus on “bridged bicyclic” molecules (and how to name them), and also briefly touch on “spiro” fused bicyclic molecules.
By the way, in the diagram below, only one “bridged bicyclic” isomer of decalin with a six-membered ring is drawn. Can you find the other bridged bicyclic isomer that also contains a six-membered ring? (Answer at bottom)
First, stereochemistry. One important note about bridged bicyclic molecules is that the two carbons forming each bridge will always be “cis” to each other, never trans, relative to the other ring.* [exceptions? yes, but you probably won’t see ’em – check the footnote if you’re curious]
Why? Like we said in the last post when discussing trans-decalin, for much the same reason that you can’t kiss yourself on the back – there just isn’t enough flexibility for this to happen without breaking something. Given the strict bond angle (109°) and length (1.50 Å) requirements of alkanes, five, six, and seven membered rings don’t have enough slack to tolerate anything other than cis ring junctions. A trans ring junction (much like a trans double bond in rings of these sizes) would simply lead to too much ring strain.
Note that in the diagram below, the “cis” ring junctions is implied by the fact that both hydrogens are on the same side (both dashes in this case). The “impossible” trans ring junction is shown in grayscale for comparison. The picture shows a model of this molecule highlighting the angle strain and Van Der Waals strain resulting from this arrangement.
Next – and this is where a lot of students get confused – we come to the topic of how to depict these things. Merely using dashes and wedges doesn’t truly capture their three-dimensional beauty. So when drawing bridged bicyclic molecules, it’s very common to show them in perspective from the side. The first reaction my students have upon seeing these drawings is utter disgust and confusion. “What is THAT?”, I recall Mike from Sault Ste. Marie asking me one night during a tutoring session.
It’s the same thing as the “top down” view, just drawn from a different perspective. Using the “top down” view is a perfectly acceptable way to draw these molecules – however, it’s vital to be able to interpret these “perspective” drawings as many bicyclic molecules in your textbook will be shown in this way.
Here’s a “flyover” view of the same molecule, from top-down to the side-view. [BTW: note how the six membered ring on the left is in the chair conformation]
The naming of bridged bicycles has its own special kind of funk. Unlike the molecules you’ve likely come across so far, which will have a clear “longest chain” or “largest ring” to start from, trying to find the place to start based on those criteria alone will likely have you going in circles. Instead, bridged bicycles are named according to a unique system of their own. based on the length of their bridges, and then the overall number of carbons in the bicycle. The figure below walks through the process.
Once you’ve run through a few examples by yourself, I think you’ll find that naming bridged bicyclic molecules is actually fairly intuitive – as long as you can interpret the diagrams correctly. [Try making a model if you’re still stuck!] See if you can follow the naming of these compounds.
See that last example? We can also use bridged bicycle nomenclature to name fused rings as well! So bicyclo[4.4.0]decane is simply another name for “decalin” (without specifying the stereochemistry, of course).
Let’s wrap up by briefly covering “spiro” fused compounds. Since both “bridgehead” positions are on the same carbon, we won’t be able to use the same “bicyclo” nomenclature as before- but the process is very similar. We simply substitute “spiro” for “bicyclo” , insert the two bridge lengths, and place the suffix as before. So the molecule below is spiro[5.4]decane. Included next door are two other examples of spiro compounds, spiro[4.3]octane and spiro[5.2]octane.
In the next post – and last in this series – we’ll talk about one final, very interesting consequence of the fact that carbons can form rings: Bredt’s Rule.
Next post: Bredt’s Rule
Did you find the other bridged bicyclic isomer of decane that contains a six-membered ring? Here it is: bicyclo[4.2.2]decane. Note that the key difference is the presence of two 2-carbon bridges (in addition to the 4 carbon bridge) in contrast to the 1 and 3-carbon bridges seen in bicyclo[4.3.1]decane.
Secondly, a note about bridged ring fusions. Like with Bredt’s rule (more on that next post) once the size of the ring perimeter gets large enough [11 seems to be the minimum], the rules can be bent a bit. There are known examples of molecules with trans bridgehead ring fusions, sometimes known as “inside-outside” isomerism. A very prominent example is the natural product ingenol, isolated from Euphorbia species. A close look at the [4.4.1]undecane ring structure reveals that the two carbons on one of the bridges are in fact trans to each other. This does lead to ring strain [about 5.9 kcal/mol according to one calculation], but not enough to render closure of the ring impossible.
By the way, ingenol is a fascinating target for testing the limits of modern organic synthesis. Isolated in 1968, it was not synthesized until 2002 by Jeffrey Winkler’s group at Penn. Subsequently the molecule has been synthesized by the groups of Wood and most recently (and impressively) by Baran. If you’re an undergraduate interested in studying organic synthesis, Mark Peczuh has written a tour de force walkthrough of Winkler’s ingenol synthesis that explains the thinking behind the synthesis line-by-line. The Baran group also has a post on their blog, Open Flask, that gives the behind-the-scenes story of their ingenol synthesis and really conveys the flavour of what working on a total synthesis project is like.
By Request: An Example Building Up A Complex Bridged Bicyclic Molecule From Its Name.
Commenter Hamid requested how to draw the structure for 6-endo-bromo-8-anti-isobutyl-1,3-exo-dimethylbicyclo[3.2.1]octane.
So here’s how you do it.
References to chemical curiosities related to bridged bicyclic rings; propellanes, strained bridged molecules, inside-outside bicyclic rings, and the total synthesis of natural products containing these features.
Kenneth B. Wiberg and Daniel S. Connor
Journal of the American Chemical Society 1966, 88 (19), 4437-4441
Prof. Wiberg was a pioneer in the synthesis and study of bicyclic hydrocarbons and synthesized many of the ‘propellanes’ in the course of his career. This paper is on the synthesis and study of the smallest bridged bicyclic ring, bicyclo[1.1.1]pentane, which later led to the synthesis of [1.1.1]Propellane. Interestingly, closing the bridge was performed using the Wurtz reaction (the sodium “cousin” of the Grignard reaction), one of its few successful applications.
- A survey of strained organic molecules
Joel F. Liebman and Arthur Greenberg
Chemical Reviews 1976, 76 (3), 311-365
An old but still nonetheless useful review on strained organic molecules.
- The structures of norbornane and 1,4-dichloronorbornane as determined by electron diffraction
J. F. Chiang, C. F. Wilcox, and S. H. Bauer
Journal of the American Chemical Society 1968, 90 (12), 3149-3157
According to this paper, bicyclo[2.2.1]heptane (more commonly known as “norbornane”) has a ring strain of 17.5 kcal/mol. The natural product camphor, responsible for the familiar smell of Vicks’ Vapo-Rub, has the same bridged ring system.
- Chemistry of bent bonds. XXX. Diels-Alder approach to inside-outside bicyclics
Paul G. Gassman and Randolph P. Thummel
Journal of the American Chemical Society 1972, 94 (20), 7183-7184
Paul Gassman (U Minnesota) was a very eminent organic chemist of the 20th century. In this paper he describes the synthesis of inside-outside bicyclic compounds using the Diels-Alder reaction.
- Bicyclo[8.8.8]hexacosane. Out, in isomerism
C. H. Park and H. E. Simmons
Journal of the American Chemical Society 1972, 94 (20), 7184-7186
The following paper after Prof. Gassman’s (Ref. #4 above) is on the same topic. Interestingly, this is submitted by H. E. Simmons (DuPont), of the Simmons-Smith reaction.
- Inside-outside stereoisomerism: the synthesis of trans-bicyclo[5.3.1]undecane-11-one
Jeffrey D. Winkler, John P. Hey, and Paul G. Williard
Journal of the American Chemical Society 1986, 108 (20), 6425-6427
This paper details a synthetic path to a small bicyclic molecule (potentially the smallest) to demonstrate in-out isomerism. This is useful for the synthesis of ingenane diterpenes, as the authors note.
- Development of a Concise Synthesis of (+)-Ingenol
Steven J. McKerrall, Lars Jørgensen, Christian A. Kuttruff, Felix Ungeheuer, and Phil S. Baran
Journal of the American Chemical Society 2014, 136 (15), 5799-5810
Ingenol is a nature product featuring a bicyclic system with in/out stereochemistry, and this paper by the laboratory of Prof. Phil Baran is on its stereospecific synthesis.