Level 1 – Case 5
Rearrangements from Tetrahydropyran
Derivatives
Key point: Crossover experiments
O
O
SnCl 4
O
O
SnCl 4
O
OH
Cl
O
O
O
O
Rearrangements from Tetrahydropyran Derivatives
When tetrahydropyranyl ethers 1 and 2 are exposed to excess (3.6 equiv) of SnCl 4
at low temperature, an oxygen to carbon rearrangement occurs, resulting in several
distinct products that are obtained as diastereomeric mixtures (Scheme 5.1). The
formation of these products could be rationalized by considering the initial generation of a carbocationic intermediate (3 or 4) from which different final products
can be obtained. For example, trapping of cation 3 by chloride ion (already present
in the medium) yields the chlorohydrins 5, whereas aldehydes 6 would be obtained from a 1,2-hydride shift in the intermediate 3. In other cases, as in 4, the
cation and the oxygen bearing the Lewis acid (still sufficiently nucleophilic) are
placed at a distance that allows the cyclization faster than the other competing
pathways, leading to bicyclic compounds like 7.
To account for the formation of carbocations 3 and 4 during the reaction, two
alternatives were considered. The first would consist on a concerted process involving simultaneous cleavage of the C-O bond and formation of the C-C bond, as
indicated by transition state 8 (path a, Scheme 5.2). The other alternative could be
a stepwise process consisting on initial C-O bond cleavage to give fragments 9
Rearrangements from Tetrahydropyran
Derivatives
Key point: Crossover experiments
O
O
SnCl 4
O
O
SnCl 4
O
OH
Cl
O
O
O
O
Rearrangements from Tetrahydropyran Derivatives
When tetrahydropyranyl ethers 1 and 2 are exposed to excess (3.6 equiv) of SnCl 4
at low temperature, an oxygen to carbon rearrangement occurs, resulting in several
distinct products that are obtained as diastereomeric mixtures (Scheme 5.1). The
formation of these products could be rationalized by considering the initial generation of a carbocationic intermediate (3 or 4) from which different final products
can be obtained. For example, trapping of cation 3 by chloride ion (already present
in the medium) yields the chlorohydrins 5, whereas aldehydes 6 would be obtained from a 1,2-hydride shift in the intermediate 3. In other cases, as in 4, the
cation and the oxygen bearing the Lewis acid (still sufficiently nucleophilic) are
placed at a distance that allows the cyclization faster than the other competing
pathways, leading to bicyclic compounds like 7.
To account for the formation of carbocations 3 and 4 during the reaction, two
alternatives were considered. The first would consist on a concerted process involving simultaneous cleavage of the C-O bond and formation of the C-C bond, as
indicated by transition state 8 (path a, Scheme 5.2). The other alternative could be
a stepwise process consisting on initial C-O bond cleavage to give fragments 9