A pericyclic reaction is a concerted reaction where formation of new bonds and cleavage of reacting — Analytical Chemistry Chemistry Question
Pericyclic Reactions and the Woodward–Hoffmann Rules
A pericyclic reaction is a concerted reaction where formation of new bonds and cleavage of reacting covalent bonds occur simultaneously, without formation of intermediates, via a cyclic transition state. You have already encountered one of the important groups of pericyclic reactions in the previous problem: the Diels–Alder reaction. Inspired by aspects of his work on the synthesis of vitamin B12 in collaboration with Albert Eschenmoser, R. B. Woodward (Nobel Laureate in Chemistry, 1965) began studies with Roald Hoffmann to understand the principals which restrict and determine the outcomes of pericyclic reactions.
Based on deductions from frontier molecular orbital theory, Woodward and Hoffmann devised a set of rules, for which Hoffmann won the Nobel Prize in Chemistry in 1981, along with Kenichi Fukui who independently reached similar rules via an alternative methods. These chemists realized that for thermally–driven chemical reactions, the highest occupied molecular orbital (HOMO) was the relevant orbital; in photochemically– driven reactions, in contrast, an electron is excited from the HOMO by light to the lowest unoccupied molecular orbital (LUMO), making this the relevant orbital.
Two types of reactions governed by the rules are the Diels–Alder reaction (an example of cycloaddition) and electrocyclic reactions. For electrocyclic reactions, the Woodward–Hoffmann rules are:
Number of π-Electrons Involved in the reaction | Thermal | Photochemical
4n | Conrotatory | Disrotatory
4n+2 | Disrotatory | Conrotatory
These rules predict the stereochemical course of reactions as shown:
Based on these rules, predict the stereochemical outcome of the following electrocyclic reactions:
i. [VISUAL]
ii. [VISUAL]
Model Answer
i. [Visual structure of trans-5,6-dimethylcyclohexa-1,3-diene or similar electrocyclic ring-opening/ring-closing product, corresponding to a conrotatory/disrotatory pathway]
ii. [Visual structure of cis-5,6-dimethylcyclohexa-1,3-diene or corresponding electrocyclic product]
These reactions are employed by nature in the synthesis of a class of natural products called the endiandric acids. All of the reactions shown below are either electrocyclic or cycloadditions (Diels–Alder).
Draw the missing structures (Y, Z, endiandric acids esters F and G) in the scheme below.
[VISUAL]
Model Answer
The solution provides the structures of the missing intermediates Y, Z and the methyl esters of endiandric acids F and G, completed as follows:
- Y is a conjugated acyclic polyene precursor derived from the Lindlar hydrogenation of the starting alkyne.
- Z is a bicyclic intermediate formed by an 8π electrocyclization of Y followed by a 6π electrocyclization.
- Endiandric acid esters F and G are tetracyclic/tricyclic adducts formed from intramolecular Diels-Alder cycloadditions of the intermediates.
Fill in the table for reactions (i)–(v).
Model Answer
The completed table is as follows:
Reaction | Diels–Alder? | electrocyclic? | Number of π electrons | con- or dis-rotatory
i | | X | 8 | Con
ii | | X | 6 | Dis
iii | X | | 6 |
iv | | X | 6 | Dis
v | X | | 6 |
Another interesting result of pericyclic reactions can be found in the bullvalene family of compounds. The relevant type of rearrangement is the Cope rearrangement, the archetype of which is shown below:
[VISUAL]
Although the compounds on both sides of the equilibrium are 1,5-hexadiene, the 13C atoms (shown as bold dots) show the movement of the electrons, and subsequently relocation of the bonds.
In this synthesis of polyketide natural products, one employs a Claisen rearrangement (similar to the Cope reaction but with one carbon in the starting material replaced with an oxygen) and electrocyclizations.
This synthesis of the polyketide natural product, SNF4435 C, features a Claisen rearrangement (similar to the Cope reaction but with one carbon in the starting material replaced with an oxygen) and electrocyclizations.
Draw the structures of the missing products in the scheme below:
[VISUAL]
Model Answer
The missing structures are:
- A: C13H25IO2Si, which is the monosilylated secondary alcohol: I-CH=C(Me-CH(OH-CH(OTBS-(CH=CH2-Me
- B: C15H27IO3Si, which is the acetylated derivative of A: I-CH=C(Me-CH(OAc-CH(OTBS-(CH=CH2-Me
- D: C16H29IO3Si, which is the methyl ester/ether obtained by methylating the free acid/phenol of C: I-CH=C(Me-CH(OTBS-CH(OMe-COOMe-(CH=CH2-Me
- E: C16H28BrIO3Si, which is the brominated derivative of D (bromination occurs on the allylic position or double bond using NBS).
How many electrocyclizations occur during the step labeled V, which is carried out under thermal conditions? Identify each cyclization by the number of π-electrons involved and as con- or dis-rotatory.
Model Answer
2 reactions: an 8π conrotatory electrocyclization followed by a 6π disrotatory electrocyclization.