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

Chapter 4 – Synthesis of carbasugars
Ox*
Ox*
i) OsO 4 , NMO, solvent
ii) reducing agent (aq)
OMe
O
102b 276
OH
Ox*
OH
O
283
Entry Solvent Reductant (pH) Workup ratio 276 : 283 * 276 / %
a t-BuOH / H 2 O Na 2 SO 3 (8) Aq 86 : 14 47
b t-BuOH / H 2 O Na 2 S 2 O 5 (4) Aq 95 : 5 68
c Acetone / H 2 O Na 2 S 2 O 5 (4) Aq 87 : 13 50
d t-BuOH / H 2 O Na 2 S 2 O 5 (4) SiO 2
‡
e CH 2 Cl 2 / H 2 O Na 2 S 2 O 5 (4) SiO 2
‡
f CH 2 Cl 2 Na 2 S 2 O 5 (4) SiO 2
‡
97 : 3 93
73 : 5 ** –
78 : 22 73
* determined by 1 H NMR of crude material; ** + 22% 201 ‡ passed thorough silica plug
Table 4.2 – dihydroxylation of the dienyl ether
The oxidation was completely regioselective giving α-hydroxyenone 276 in high yield,
although surprisingly accompanied by dienone 283. The presence of greater amounts
of the dienone under moderately alkaline quench for a short period of time (c. 1 hr,
entry a) implies that enone 276 is highly base sensitive. This was confirmed during
the attempted benzylation of enone 276 under the conditions employed by Lockwood
in the modification of carotenoids which returned dienone 283 (Scheme 4.15). 173
Ox*
O
276
OH
pKa in DMSO
i) LiHMDS (1.2 eq)
CH 2 Cl 2 , -20 °C
ii) BnBr (1.3 eq)
O
OMe
Ox*
O
283
Ph
O
OH
24.6 174 22.9 174
50%
80% conv
OMe
HO
Ox*
O
O H
284
30.3 175
Scheme 4.15 – autoxidation of 276
Under the strongly basic conditions, it is unclear whether this oxidation of 276
occurred during the reaction – solvents were not degassed – or upon workup.
However, a small excess of base returning a relatively high yield of dienone lends
143