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

Chapter 4 – Synthesis of carbasugars
O
Me
Me
i) H -
HO
HO
O
O
O CO 2
OH
213 328
OH
ii) H 2 O
HO
OH
α-L-Mannose
analogue
329
OH
Scheme 4.45 – proposed reduction-hydrolysis of lactone 213
4.5.1.a Initial studies of lactonisation-epoxidation strategy
It was anticipated that lactonisation could be induced under similar conditions to those
found before (section 4.2.8), but that replacing the reductive quench with an aqueous
one might increase yield of lactone and return some starting material. As before, the
alkylation was left overnight, but instead of the standard methanol/THF-borohydrdride
quench, aqueous ammonium chloride was added to the reagents in dichloromethane
with vigorous stirring.
Ox*
i) MeOTf, CH 2 Cl 2
16 hr
O
OH ii) NH 4 Cl (aq) O
8 hr
OH
213 328
OH
36 %
97% conv.
Scheme 4.46 – lactonisation
Lactone 328 was isolated in a similar quantity to the previous conditions, and despite
complete conversion of the oxazoline, no other products could be identified before or
after purification. That similar amounts of lactonisation were seen under reductive and
aqueous quenches lends support to the conclusion that lactonisation occurs during
alkylation.
Epoxidation of the resulting olefin went cleanly with no other products visible in the
crude NMR (Scheme 4.47). There was, however, a striking difference between the
carbon NMR of this compound and its diastereomer 307; the carbonyl of the latter was
only observable with a relaxation time of 25 seconds, whilst the carbonyl of 329 was
observable with a standard relaxation time of 1 second. Since spin relaxation of 13 C
nuclei is assisted by nearby protons in a through-space interaction, this is explained by
167