Part 2(i): Electrocyclic Reactions Second Year Organic Chemistry Course CHM3A2 Frontier Molecular Orbitals and Pericyclic Reactions Part 2(i): Electrocyclic Reactions An electrocyclic reaction involves the formation of a -bond between the termini of a linear conjugated -system by two of the -electrons - or the reverse reaction.

Electrocyclic Reactions CHM3A2 – Introduction to FMOs – – Learning Objectives Part 2(i) – Electrocyclic Reactions After completing PART 2(i) of this course you should have an understanding of, and be able to demonstrate, the following terms, ideas and methods. (i) An electrocyclic reaction involves the formation of a -bond between the termini of a linear conjugated -system by two of the -electrons - or the reverse reaction. (ii) Electrocyclic reactions are stereospecific. The stereospecificity being afforded by the disrotatory or conrotatory nature of the bond making/breaking process (iii) 4-electron systems are conrotatory when thermally promoted, (and disrotatory when photochemically promoted - CHM3A2). (iv) 6-electron systems are disrotatory when thermally promoted (and conrotatory when photochemically promoted - CHM3A2). (v) The disrotatory or conrotatory process involved in the bond making/breaking process is controlled by the HOMO (thermal reaction) or SOMO (photochemical reaction - CHM3A2) of the linear conjugated -system which either is the starting material or product.

6p-Electron Systems RS Meso RR Enantiomers SS

4p-Electron Systems RR Enantiomers SS RS Meso

HOMOs of Polyenes A new s-bond is forming at the termini of each of the polyene systems. Thus, it is clear that the p-system of the polyene systems must be interacting in some fashion. Analysis of the polyenes has shown that by considering the HOMOs, and rotating the termini of them to overlap them in an in-phase fashion produces the correct stereochemical outcome. The termini of the orbitals can be rotated in two manners referred to as: Conrotatory, Disrotatory.

Disrotatory Motion: Dark/Dark In-phase Meso

Disrotatory Motion: Light/Light In-phase Meso

Conrotatory Motion: Dark/Dark In-phase RS Enantiomer

Conrotatory Motion: Light/Light In-phase SR Enantiomer

4n+2 p Electron Electrocyclic Reactions 1, 3, 5-Hexatriene 6 p AOS 6 p MOs Electrons y 3 = HOMO two nodes (7/3) y 3 – H O M Disrotatory

y 3 – H O M M e M e Dark/Dark Or Light/Light DISROTATORY DISROTATORY Meso RR and SS (enantiomers)

4n p Electron Electrocyclic Reactions

4n p Electron Electrocyclic Reactions Butadiene y 2 – H O M 4 p AOS 4 p MOs Electrons y 2 = HOMO one node (5/2) Conrotatory

y 2 – H O M Dark/Dark Or Light/Light CONROTATORY CONROTATORY RR and SS (enantiomers) see next slide Meso

Two alternative and equivalent modes of conrotatory in-phase overlap Enantiomer Formation y 2 – H O M Two alternative and equivalent modes of conrotatory in-phase overlap CONROTATORY RR S A Pair of Enantiomers

Coping with Ring Opening Reactions 1. Draw out the p-HOMO of the product without the substituents 2 HOMO

2. Draw out the MO of the Starting material Same Phase Bonding: Must be in phase! 2 HOMO

3. Open the C-C bond two afford the HOMO of the product CONROTATORY

Product stereochemistry 4. Decide how the substituents move CONROTATORY 2 HOMO

Rules for Electrocyclic Reactions _______________________________________________________Number of -Electrons Thermal Photochemical (CHM3A2) 4n CONrotatory DISrotatory 4n + 2 DISrotatory CONrotatory _______________________________________________________ Photochemical reactions will be dealt with in the third year course (CHM3A2), where the first electronically excited stated state becomes the HOMO.

Electrocyclic Reactions CHM3A2 – Introduction to FMOs – – Summary Sheet Part 2(i) – Electrocyclic Reactions An electrocyclic reaction involves the formation of a -bond between the terminals of a linear conjugated -system by two of the -electrons – or the reverse process. Electrocyclic reactions are either 'allowed' or 'forbidden' – and they are stereospecific, occurring by either a so-called conrotatory or disrotatory motion. Electrocyclic reactions can be brought about by heat (CHM2C3B), by ultraviolet irradiation (CHM3A2), and sometimes by the use of metal catalysts (CHM3A2). They are nearly always stereospecific. In many cases, detection of their stereospecificity depends on distinguishing chemically similar stereoisomers - a problem which has been overcome mainly by the development of spectroscopic methods of structure determination, especially NMR spectroscopy. Thus, the recognition that stereospecific electrocyclic reactions form a coherent group extends only over the last quarter of a century. Nowadays, the group includes some important synthetic reactions as well as some of the most clear cut examples of the successful predictive power of orbital symmetry theory. In the case of 6p systems, the thermal ring closure of 1,3,5-hexatrienes to conjugated cyclohexadienes is stereospecific - and disrotatory - as the theory predicts. Ring closure of 1,3, 5-hexatrienes is a relative facile process relative to butadiene ring closure which generates a highly strained butadiene derivatives. In the case of 4 systems, the thermal ring opening of cyclobutenes to butadienes is stereospecific - and conrotatory - as the theory predicts. In most cases, the ring opening goes to completion and there are very few examples of the reverse process, the thermal cyclisation of butadienes. Fused cyclobutenes, however, are thermally rather stable, especially those in which the second ring is five- or six-membered.

Exercise 1: 4n+2 p Electrocylic Systems The triene 1 undergoes a thermal electrocyclic cyclisation. Using FMOs identify all the products. 1

Answer 1: 4n+2 p Electrocylic Systems The triene 1 undergoes a thermal electrocyclic cyclisation. Using FMOs identify all the products. 1 y 3 – H O M DISROTATORY R S Dark R S Light Superimposable Mirror Images Exactly the same compound MESO Compound

Exercise 2: 4n+2 p Electrocylic Systems The two diastereoismeric trienes 1 and 2 undergo thermal electrocyclic cyclisation reactions each affording a pair of disubstituted conjugated cyclic dienes. Identify all four products by constructing the transition state geometries, and state the stereochemical relationships that exist between the pairs of stereoisomers formed from each reaction and the stereochemical relationship of the products between the pair of reactions 1 2

Answer 2: 4n+2 p Electrocylic Systems The two diastereoismeric trienes 1 and 2 undergo thermal electrocyclic cyclisation reactions each affording a pair of disubstituted conjugated cyclic dienes. Identify all four products by constructing the transition state geometries, and state the stereochemical relationships that exist between the pairs of stereoisimers formed from each reaction and the stereochemical relationship of the products between the pair of reactions 1 2 DISROTATORY y 3 – H O M DISROTATORY R S Dark R S Light R Dark S Light Enantiomers Diasteroisomers Enantiomers

Exercise 3: 4n p Electrocylic Systems The cyclobutadiene derivative undergoes an stereospecific electrocyclic ring opening reaction to afford a single product. Utilise FMOs to identify the product. 1

Answer 3: 4n p Electrocylic Systems The cyclobutadiene derivative undergoes an stereospecific electrocyclic ring opening reaction to afford a single product. Utilise FMOs to identify the product. 1 CONROTATORY y 2 HOMO

Exercise 4: A Cascade Electrocylic System Use FMOs to predict the stereochemical outcomes in the reaction scheme below.

Answer 4: A Cascade Electrocylic System Use FMOs to predict the stereochemical outcomes in the reaction scheme below. y 4 (3 nodes 9/4) of 1, 3, 5, 7-octatetraene y 3 (2 nodes) of 1, 3, 5-hexatriene M e H M e 4n - CONROTATORY (4n + 2) - DISROTATORY M e H H M e Dark/Dark Dark/Dark M e M e H H M e Light/Light Light/Light

Exercise 5: Tandem Electrocyclic Reaction Use FMOs to predict the stereochemical outcomes in the reaction scheme right. In principle, there are two possible products. Which will be formed in highest yield. Justify your answer.

Product. Least sterically hindered Answer 5: Tandem Electrocyclic Reaction Use FMOs to predict the stereochemical outcomes in the reaction scheme right. In principle, there are two possible products. Which will be formed in highest yield. Justify your answer. The arrow pushing mechanism reveals that the reaction involves the ring closure of two 1,3,5-hexatriene systems. Thus, need to consider y3 HOMO of 1, 3, 5-hexatriene. Light Light H Thermodynamic Product. Least sterically hindered Disrotatory of both triene systems Light Dark H

Exercise 6: Complex Electrocyclic Reaction Cyclooctatetraene undergoes an electrocyclic ring closure forming only the cis-isomer as depicted right. Rationalise this result using FMOs.

Answer 6: Complex Electrocyclic Reaction Cyclooctatetraene undergoes an electrocyclic ring closure forming only the cis-isomer as depicted right. Rationalise this result using FMOs. 4p Electron Process H H CONROTATORY y 2 HOMO Butadiene 6p Electron Process H y 3 HOMO 1,3,5-Hexatriene H DISROTATORY Thus, the reaction must proceed by a 6 p electron process, despite the 4 p electron process being possible by FMO theory. Reasons for formation of cis-isomer are possibly two-fold: (i) cis-isomer is the thermodynamically more stable product, and/or (ii) the aromatic 6p electron aromatic transition state is lower in energy than the 4p electron anti-aromatic transition state.

Exercise: 4n p Electrons Electrocyclic Reactions Using FMOs rationalise why the two diastereoisomers have such different reactivities.

Answer: 4n p Electrons Electrocyclic Reactions Using FMOs rationalise why the two diastereoisomers have such different reactivities.