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

3.2 – Oxazoline removal
3.2.5.b N-Alkylation
Meyers’ preferred method of oxazoline removal was alkylation-reduction followed by
hydrolysis of the oxazolidine to reveal the aldehyde (section 3.2.1.b). Early attempts
to reproduce this on two model compounds failed work after repeated attempts.
Ph Ph
O
N
i) MeOTf, 10 hr
then NaBH 4
ii) (CO 2 H) 2 , rt, 36 hr
THF/H 2 O
poor mass recovery,
no isolable product
102a
Ph Ph
O N
c-Hex
101m
i) MeOTf, 5 hr
then NaBH 4
ii) (CO 2 H) 2 , rt, 16 hr
THF/H 2 O
poor mass recovery,
no isolable product
Scheme 3.34 – failed alkylation-reduction-hydrolysis reactions
However, enone 201 underwent a smooth alkylation-reduction sequence to give
oxazolidine 222 as a single observable diastereomer isolated by flash column
chromatography. The relative stereochemistry of 222 was established by forward
reaction (section 4.4.2).
Ph Ph
Ph Ph
O
N
O
N
O
H
MeOTf, 16 hr
Conditions, rt
then NaBH 4
O
201
OH
222
70%
>95:5 d.r
OH
223
>95:5 d.r
Entry Conditions Time conversion / %
a THF/H 2 O, (CO 2 H) 2 40 hr 70
b THF/H 2 O, (CO 2 H) 2 3 d 100
c SiO 2 , CH 2 Cl 2 10 d 50
d THF/pH 9 buffer 24 hr 0
Table 3.11 – hydrolysis of 2-cyclohexyloxazoline
122