Practice Problems in Pericyclic Reactions.

Answers prepared by Henry Rzepa for the second year course at the Department of Chemistry, Imperial College.

Qu 32

4n+2, Huckel 2+4 cycloaddition to give [A], followed by 4n+2 Huckel cycloelimination. Two possible regio-isomers are possible for [A] (bonus mark if you spotted this).
Electrocyclic 4n Mobius ring opening (as per lectures) followed by rotation around the single bond indicated and electrocyclic ring closure to distribute the deuterium atoms as shown.
Two successive electrocyclic reactions, the first 4n via Mobius to give the trans dimethyl stereochemistry, the second 4n+2 via Huckel to give the cis-ring fused system. Then 4n+2 Huckel cycloaddition (two possible stereoisomers, but one is more sterically hindered than the other) followed by cycloelimination of a cyclobutene, which then opens in a 4n Mobius electrocyclic reaction to give the trans hexadiene. This problem becomes more tractable if the starting material is redrawn into a cyclisable form by rotating about formally single bonds, hence the hint!
A Mobius 4n 2+2 cycloaddition typical of that found for many ketenes gives a cyclobutene, which opens via an electrocyclic 4n Mobius to a diene. A second 4n+2 electrocyclisation is followed by a [1,7] sigmatropic shift of the H atom via a Mobius (antarafacial) migration. If traces of acid or base are present, then a normal catalysed keto-enol tautomerism will occur instead.

Qu 33
Photolysis of U results in a carbene, which undergoes a 4n [1,2] sigmatropic shift (the Wolff rearrangement) to give the ketene V. This undergoes a p2s + p2a cycloaddition (Mobius transition state) with the alkyne to give the cyclobutenone W, which in turn opens by an electrocyclic 4n reaction (Mobius transition state) to give either X (conrotation in one direction) or XÕ (conrotation in the other direction). Only X is capable of further 4n+2 electrocyclisation (Huckel transition state) to give Y, which then tautomerises to give the phenol Z. For more details, see R. L. Danheiser et al, J. Am. Chem. Soc., 1990, 112, 3093.

Qu 34
A to B is a typical [3,3] sigmatropic rearrangement (two double bonds separated by three s bonds) and is a 4n+2 thermal process proceeding via a Huckel transition state with suprafacial stereochemistry. The enol so formed rapidly tautomerises to the ketone C, which then undergoes an ene reaction (two s bonds formed, one broken) to form D, also a 4n+2 Huckel reaction. Either one of the two hydrogen atoms on the prochiral CH2 group (differentiated as Pro-R and Pro-S) can be transferred resulting in E or Z double bond isomers, via a transition state the more stable of which leads to D and the less stable to E. D/E again have the pattern of two double bonds separated by three sigma bonds, which allows another [3,3] sigmatropic reaction to occur, via a chair 4n+2 Huckel transition state in which the new C-C bond is formed suprafacially to create two new chiral centres in F/H (see models). This rapidly and non-stereospecifically cyclises to the final product G. The other double bond isomer E which [3,3] cyclises via another chair transition state to H does so with the opposite configuration at the benzylic carbon (see the 3D models to really convince yourself this is true). For more details, see L. Barriault and I. Denissova, Organic. Letters, 2002, 4(8), 1371-1374. 3D models for these transition states can be viewed at http://www.ch.ic.ac.uk/local/organic/tutorial/rzepa6/.

Qu 35
See here.

Qu 36
See here.

Qu 37
See here.

THE END