In addition to the A and B rings, Williams et al. also used an interesting cationic
process to build the D ring contained in phorboxazole A (Scheme 18) [40]. The
transformation involved formation of the triflate from 57 followed by expulsion of
triflic acid to generate an allylic carbocation. Subsequent internal trapping of the
transoid allylic cation intermediate by the C22 methoxymethyl ether and concomitant dealkylation of the resultant oxonium species provided THP 58 in moderate
yield (55 %) as the sole diastereomer.
White and coworkers reported perhaps the most noteworthy example of nucleophilic substitution in a complex setting. The late-stage closure of the A ring of
phorboxazole A proceeded smoothly under mild conditions [41, 42]. Exposure of
mesylate 59 to Et 3 N afforded 2,6-trans THP 60 in high yield (86 %) as a single
diastereomer (Scheme 19).
O
OPMB
OTES
N
O
O
MeO
MeO
OTBDPS
D
F
E
PivO
OH
OPMB
OTES
N
O
O
MeO
MeO
OTBDPS
F
E
PivO
MOMO
Tf 2 O, Py
CH 2 Cl 2
–20 ºC
55%
57
58
Scheme 18 Carbocation-induced D ring closure en route to phorboxazole A [40]
O
N
O
O
OPMB
TBDPSO
N
O
O
MeO
MeO
MeO
OTBDPS
Br
D
B
C
F
E
O
N
O
O
OPMB
TBDPSO
O
N
O
O
MeO
MeO
MeO
OTBDPS
Br
OH
MsO
Et 3 N, CH 3 CN, D
D
B
C
F
A
OTBDPS
OTBDPS
59
60
E
86%
Scheme 19 Late-stage displacement strategy to the A ring of phorboxazole A [42]
Synthesis of Saturated Tetrahydropyrans
55