Pericyclic Reactions: Electrocyclisations. How to Use Woodward-Hoffmann Rules in Organic Chemistry 2
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- Опубликовано: 12 сен 2024
- How to use the Woodward-Hoffmann Rules to determine if a pericyclic electrocyclisation reaction is proceeds in a disrotatory or conrotatory fashion under either thermal or photochemical conditions.
Complementary Video - Part 1: Cycloadditions
• Pericyclic Reactions: ...
Citation for Nicolaou Endiandric Acid Synthesis: Nioloaou, KC et al. J. Am. Chem. Soc. 1982, 104, 20, 5560-5562
doi.org/10.102...
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Pericyclic electrocyclisation reactions can be identified as a distinct class of pericyclic reaction. During a ring-closing mechanism, one sigma bond is formed between two ends of a single longer conjugated pi-system and there is an overall shortening of the total pi-system in the product when compared to the starting material. Electrocyclic ring-opening mechanisms are also possible as the exact reverse of the ring-closing process. Forming one new sigma bond in a ring-closing is often the thermodynamic driving force (enthalpy mainly) for these mechanisms - for example a carbon-carbon sigma bond is normally stronger than the energy lost by shortening a conjugated system. However, if this results in ring strain or a weak sigma bond, the reverse ring-opening process is favoured.
The Woodward-Hoffmann Rules were developed as a quick way for organic chemists to rationalise experimental observations and make predictions about pericyclic reactions. The Woodward-Hoffmann Rules have their basis in quantum mechanics and molecular orbital theory (MO theory) and are concerned with analysing the whole set of molecular orbitals associated with a fully conjugated pi system. The Woodward-Hoffmann Rules are a summary of the results obtained by setting up correlation diagrams that track molecular orbital symmetry conservation in a reaction as a reactant is converted into a product via a transition state. All electrocyclisations are allowed, but depending on the reaction conditions - either thermal or photochemical - the reaction proceeds either in a disrotatory or conrotatory fashion. This has important consequences on the stereochemistry of a product of a pericyclic electrocyclization and hence these reactions can be used to install otherwise complicated stereochemistry on demand by careful choice of conditions.
Firstly a three-dimensional diagram should be drawn to analyse a specific electrocyclisation. The pi system involved should be identified and labelled with the number of electrons that it contains. It is conventional to add pi or sigma qualifiers as subscripts to the left of the electron count.
It is sensible to work with as few defined pi systems as possible to simplify the Woodward-Hoffmann analysis. This is done by remembering to recognise that adjacent pi bond, lone pairs and/or empty p-orbitals are considered to be conjugated, forming one larger delocalised molecular orbital system, which usually provides a setup for the electrons to lower their total combined energy. In analysing pericyclic electrocyclisations, it is usually possible to analyse using the Woodward-Hoffmann rules an arrangement with only a single pi system for ring closure. Proving how the ring closure works means that a ring opening mechanism must proceed via the same disrotatory or conrotatory mode. With one sysyem being considered, the single pi component is then assigned as suprafacial or antarafacial depending on what the conditions require to as part of the Woodward-Hoffmann rules.
The Woodward-Hoffmann Rules tell you that: if you count the number of suprafacial components with 4n+2 electrons (where n is an integer) and add that number to antarafacial components with 4n electrons, then the reaction will be thermally allowed when the total sum is an odd number. If the sum is an even number, the reaction is only possible/allowed under photochemical reaction conditions and will not proceed if only heated.
This video on pericyclic reactions involves a retrosynthesis using both a cycloaddition (Diels-Alder) and two electrocyclization reactions to form a natural product with a cage structure. These reactions in total synthesis are showcased in the Nicolao synthesis of Endiandric acid A in 1982. The retrosynthesis begins by identification of two cyclohexenes. Disconnection of one of these cyclohexenes by Diels-Alder reaction (pericyclic [4+2] cycloaddition) leads back to two dienes, one of which is inside a 6-membered ring. This cyclohexene can then be disconnected by electrocyclisation to a triene, breaking open a the cyclobutene motif. The correct stereochemistry is attained by doing this under thermal conditions so the process is disrotatory. The triene in a 8-membered ring can also be made by electrocyclisation, also under thermal conditions, to ensure a conrotatory process.
Really enjoyed seeing you explain the Woodward Hoffman rules and demonstrate how to use them, didn't really understand how to use them especially the suprafacial and antarafacial parts until I saw this video :D
What are some tips on getting good at organic chemistry mechanisms? I want to try deepen my understanding of organic chemistry and your videos have been helping to motivate me to study as they highlight how interesting the subject is.
Thanks 🙂 If I’m totally honest, practice is by far the most effective way of getting good and try not to just memorise things. It’s more like learning maths I reckon - focus on methods and patterns between reactions. If you haven’t done so already, a solid understanding of qualitative molecular orbital theory is a really good way to unpack problems logically
The legend is back! Love your videos. Joy to watch every time
:) Thanks
Hi! Will there be any organic chemistry videos with graduate discussion level? I think a lot of your viewers will appreciate it.
Hi. My next one which I’m just editing at the moment is a more advanced catalysis discussion. Is there any topic that would be of particular interest at that level that I can have a think about? I have written postgrad lecture courses in the past so I’m up for pitching the level up for some videos if there’s demand 🙂
@@CasualChemistry Well, I am mostly into organic chemistry, so a somewhat deeper dive into rethrosynthetic analysis of complex structures would be of interest. Also synthesis of polycyclic molecules with hetero atoms would be a much appreciated theme. Also, maybe a monthly (weekly?) overview of organic chemistry article(s) which you think have (may have) high impact in the field. Molecular orbitals in synthetic chemistry. You caught me by surprise with your question... :) But the topics above are the first ones that come to my mind. Maybe you could conduct a survey among the subscribers to find out more about their preferences. I like all your videos, but the ones on rethrosynthesis are my favourite.
is there a video of Woodward-Hoffman rule used for a sigmatropic rearrangement? i.e why a [1,3] hydride shift not work but a [1,5] hydride shift does? would be appreciated.
I haven’t done that yet, but sigmatropic stuff is the obvious next one I should look into making in this series. I’ll add it to my thinking-about list as I need to work out a coherent way of joining the ideas together concisely. That class of pericyclic reaction has a lot more variety of possibilities involved.
s,s,a is also odd but it is giving the trans product. What will we know if we dont have product?
2s,2s,2a will sum to 2, so even, in the Woodward-Hoffmann calculation as they're all part of the (4q+2) sequence and you only count the s ones. The product from any of these reactions depends on the geometry (E/Z) of any starting material and the conditions used. You then need to pick CON or DIS and work through the rotation as the final step to determine a product.
@@CasualChemistry yep.. got it… can u please make a video on ring opening reactions?
Probably not a specific one but might use them as part of a synthesis. To be honest I’d always advise dealing with the ring opening by solving the reverse ring closure (which is much simpler) and asserting that both forward and reverse reaction must be the same type of rotatory