Pericyclic Reactions: Electrocyclisations. How to Use Woodward-Hoffmann Rules in Organic Chemistry 2

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: Cycloadditions ...  

Citation for Nicolaou Endiandric Acid Synthesis: Nioloaou, KC et al. J. Am. Chem. Soc. 1982, 104, 20, 5560–5562
https://doi.org/10.1021/ja00384a080


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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.