3.

O12 - An Introduction to Reaction Stereoelectronics 2014-2015 OUTLINE ANSWERS

(a)

(i iii) Protonation of the substrate (synthesised by a Diels-Alder reaction) by formic

acid effects a Grob fragmentation. Re-drawing of this intermediate reveals that
the two stereogenic centres bearing methyl groups are carried through from the
starting material and map directly into the product. The decalin framework is
established by a vinologous Prins-type ring-closure which can give either the
axial or equatorial cationic isopropyl substituent depending on the relative
geometry of the interacting alkenes. The equatorial product predominates as
this is the thermodynamically preferred product. The cation is trapped out by
the formate anion and the methyl dienyl ether is hydrolysed to the enone in the
aqueous acidic conditions.

Problem solving. Grob fragmentations were discussed in lectures but not this
one. Envisaged mark schemes: 2 marks for correct arrow pushing for Grob
fragmentation; 2 marks for naming the stereoelectronic interactions; 2 marks for
indicating the anti-periplanar orbitals/bonds; 2 marks for correct arrow pushing for
remaining steps and 2 marks for indication of orbitals and co-planar arrangement of orbitals for the ring-closure.
(10 marks)
(b)

(i)

The order of events here is uncertain. The transformation could involve acid
catalysed intramolecular aldol condensation to give a decalin enone
intermediate in which the C-C double bond is aligned with the cyclopropane
such that facile fragmentation is possible to generate a tert-carbocation and
extended dienol (partly driven by relief of ring-strain).

Alternatively, protonation of the cyclohexanone could induce ring-opening of

the cyclopropane first, followed by an acid catalysed intramolecular aldol
condensation.

Either mechanism would attract full marks.

(ii)

Protonation of the endo hydroxyl group sets up a Wagner-Meerwein 1,2-shift

of the anti-periplanar C-C bond to yield a tertiary carbocation which undergoes
elimination to give the exo-methylene product. Direct E2 elimination on
protonation of the hydroxyl group is disfavoured because no protons have the
correct anti-periplanar orientation. The direction of the final elimination can
only take place in the manner shown as the alternative would lead to an antiBredt bridgehead alkene.

(iii)

Acid catalysed intramolecular aldol condensation (as for part ii, above) gives
an enone intermediate in which the C-C double bond is aligned with the
bridgehead C-C bond such that facile fragmentation is possible to generate a
tert-carbocation and extended dienol which becomes protonated at the position to regenerate an enone.

(iv)

Acid catalysed retro-aldol fragmentation driven by relief of strain in the

cyclobutane then tautomerism to give the isomeric enol which undergoes a 6exo-trig intramolecular aldol condensation.

Problem solving. Various rearrangements and fragmentations were discussed in

lectures but none of these ones. Envisaged mark schemes: 2 marks for correct arrow
pushing; 3 marks for indication of required anti-peripanar alignments and indication
of orbitals involved in the key rearrangements or fragmentations.
(5 marks each)