A Route to Carbasugar Analogues - Jonathan Clayden - The ...

4.2 – Carbasugar synthesis
of the oxazoline as depicted, with none to the other face; showing that the cyclic
system is very rigid in solution. The oxazoline group remained axial throughout the
synthesis (identified by J H2–H3 ), presumably since the cumulative equatorial preference
of the isopropyl and methyl groups (c. 3.5 kcal mol -1 ) was greater than the oxazoline
(methyl ester c. 1.5 kcal mol -1 ). The crystal structure of a later product is consistent
with the energy minimised structure presented (Scheme 4.17). With this result in hand
we were confident that the proposed synthesis would proceed with high levels of
substrate control.
4.2.3 Oxidation of the dienyl ether
The regioselective oxidation of conjugated silyl enol ethers was developed by
Rubottom to give α-hydroxy enones. 167 This was achieved by using the electrophilic
oxidant mCPBA which oxidises the electron rich olefin more rapidly and has since
been applied to enol ethers. 168 Unfortunately, when diene 102b was subjected to
modified Rubottom conditions, enone 276 was isolated in very low quantities with
many unidentified by-products, including significant amounts of enone 201.
Ox*
Ox*
T n 276 /%
OMe
102b
mCPBA (n eq)
CH 2 Cl 2 , T °C
O
276
OH
20 3.0 7
– 40 1.2 3
– 78 1.2 n.r.
Table 4.1 – attempted Rubottom oxidation of the dienyl ether
In a similar manner to Rubottom, McCormick used osmium tetroxide to oxidise
unconjugated silyl enol ethers to α-hydroxy ketones. 169 Since dihydroxylation is a
pericyclic process 170 involving the HOMO of the olefin, the more electron rich alkene
will again react first. Enol ether 102b was subject to the conditions of Upjohn 171
(entries a-d, Table 4.2) and Poli 172 (entries e, f).
142