Brimble et al. [127] for the synthesis of bis(benzannulated)-spiroacetals 238
(Scheme 58). Deprotection of the EOM group in chromones 236 prompted intramolecular oxa-Michael addition of the resulting phenol in most cases. In the two
examples where only the free phenol 237 was recovered, the spirocyclization could
be induced by heating the neat phenol with dry potassium carbonate under microwave irradiation. The resulting bis(benzannulated) 6,6-spiroacetals were obtained
in low to moderate yields.
Cascade sequences involving Michael additions have also been reported recently
for the synthesis of spiroacetals. An oxa-Michael initiated spirocyclization cascade
sequence has been used in the synthesis of berkelic acid by both Fu ¨rstner et al. [128]
and Brimble et al. [129] (Scheme 59).
Brimble and coworkers used a three-step HWE/oxa-Michael/acid-catalyzed
cyclization sequence to access the simplified spirocyclic core 243. Unfortunately,
application of this method to a more complex substrate in order to obtain the
substituted tetrahydrofuran was unsuccessful [130]. However, Fu ¨rstner and
coworkers were able to effect a similar cascade from enone 244 in one step,
affording tetracyclic spiroacetal 245 in excellent yield as a single isomer.
Alternatively, the oxa-Michael addition can be used as the final step in the
spirocyclization cascade. Wulff et al. [131] have reported a tandem
desymmetrization/oxa-Michael addition in their studies toward the spiroacetal
Scheme 57 Oxa-Michael approach towards norhalichondrin B [126]
230
M.A. Brimble and L.A. Stubbing
(Scheme 58). Deprotection of the EOM group in chromones 236 prompted intramolecular oxa-Michael addition of the resulting phenol in most cases. In the two
examples where only the free phenol 237 was recovered, the spirocyclization could
be induced by heating the neat phenol with dry potassium carbonate under microwave irradiation. The resulting bis(benzannulated) 6,6-spiroacetals were obtained
in low to moderate yields.
Cascade sequences involving Michael additions have also been reported recently
for the synthesis of spiroacetals. An oxa-Michael initiated spirocyclization cascade
sequence has been used in the synthesis of berkelic acid by both Fu ¨rstner et al. [128]
and Brimble et al. [129] (Scheme 59).
Brimble and coworkers used a three-step HWE/oxa-Michael/acid-catalyzed
cyclization sequence to access the simplified spirocyclic core 243. Unfortunately,
application of this method to a more complex substrate in order to obtain the
substituted tetrahydrofuran was unsuccessful [130]. However, Fu ¨rstner and
coworkers were able to effect a similar cascade from enone 244 in one step,
affording tetracyclic spiroacetal 245 in excellent yield as a single isomer.
Alternatively, the oxa-Michael addition can be used as the final step in the
spirocyclization cascade. Wulff et al. [131] have reported a tandem
desymmetrization/oxa-Michael addition in their studies toward the spiroacetal
Scheme 57 Oxa-Michael approach towards norhalichondrin B [126]
230
M.A. Brimble and L.A. Stubbing