geometry and rigidity of the bicyclic skeleton). This will be illustrated with the
synthesis of an imino-C-disaccharide (Scheme 42). However, in the absence of
electrophilic reagents and on heating, enolates derived from these 7-oxanorbornane
derivatives undergo 7-oxa ring opening with the formation of the corresponding
cyclohex-3-en-1-ols [240–247]. This has been exploited in several syntheses of
natural products and analogues of biological interest [206, 248–250]. For instance,
racemic illudin M (shows in vitro selective toxicity toward tumor cells [251]) has
been prepared as outlined in Scheme 31 [249].
We have seen in Scheme 28 that oxanorbornanone (À)-175 can be converted
into the enoxysilane 176 without 7-oxa ring opening when the silylation employs
TBSCl and imidazole at 0
C. The same reaction with TBSOTf (the triflate TBSOTf
is a much better oxophilic agent than the chloride TBSCl and thus assist the
heterolysis of the ethereal bridge) and Et 3 N at 20
C converts (À)-175 into
cyclohexenone (À)-193. This compound is a precursor for the preparation of
(À)-conduritol B and of (+)-conduritol F [229, 252, 253] and of cyclitols
(Scheme 32).
An example of ethereal bridge opening involving a 7-oxanorborn-2-yl sulfone is
given in Scheme 33 [254]. Diels–Alder addition of the difluoroacrylate 194 to furan
gives the corresponding cycloadduct 195. Its alkene moiety at C5–C6 adds to
benzenesulfenyl chloride with high exo face stereoselectivity and regioselectivity
because of the participation of the 2-endo carboxylic group that leads to the
formation of tricyclic lactone 196. Reduction of the lactone with LiAlH 4 in THF
gives a triol that is protected as an acetonide. Then, the 6-endo-hydroxy group is
converted into the corresponding benzyl ether. Oxidation of the 5-exo-phenylthio
group with mCPBA generates the corresponding sulfone 197. The treatment of 197
with BuLi in THF at low temperature induces a smooth isomerization into
O
O
BnO
HO
O
OH
TBSO
TBSO
OH
OH
HO
HO
OH
OH
HO
HO
(-)-175
Et 3 N
PhH, 20
o
C
(-)-Conduritol B
(+)-Conduritol F
(-)-193
1) H 2 /Pd
2) TBSOTf
94%
Scheme 32 The conversion of “naked sugars” into conduritols
Scheme 31 Synthesis of rac-illudin M
Synthesis of 7-Oxabicyclo[2.2.1]heptane and Derivatives
171
synthesis of an imino-C-disaccharide (Scheme 42). However, in the absence of
electrophilic reagents and on heating, enolates derived from these 7-oxanorbornane
derivatives undergo 7-oxa ring opening with the formation of the corresponding
cyclohex-3-en-1-ols [240–247]. This has been exploited in several syntheses of
natural products and analogues of biological interest [206, 248–250]. For instance,
racemic illudin M (shows in vitro selective toxicity toward tumor cells [251]) has
been prepared as outlined in Scheme 31 [249].
We have seen in Scheme 28 that oxanorbornanone (À)-175 can be converted
into the enoxysilane 176 without 7-oxa ring opening when the silylation employs
TBSCl and imidazole at 0
C. The same reaction with TBSOTf (the triflate TBSOTf
is a much better oxophilic agent than the chloride TBSCl and thus assist the
heterolysis of the ethereal bridge) and Et 3 N at 20
C converts (À)-175 into
cyclohexenone (À)-193. This compound is a precursor for the preparation of
(À)-conduritol B and of (+)-conduritol F [229, 252, 253] and of cyclitols
(Scheme 32).
An example of ethereal bridge opening involving a 7-oxanorborn-2-yl sulfone is
given in Scheme 33 [254]. Diels–Alder addition of the difluoroacrylate 194 to furan
gives the corresponding cycloadduct 195. Its alkene moiety at C5–C6 adds to
benzenesulfenyl chloride with high exo face stereoselectivity and regioselectivity
because of the participation of the 2-endo carboxylic group that leads to the
formation of tricyclic lactone 196. Reduction of the lactone with LiAlH 4 in THF
gives a triol that is protected as an acetonide. Then, the 6-endo-hydroxy group is
converted into the corresponding benzyl ether. Oxidation of the 5-exo-phenylthio
group with mCPBA generates the corresponding sulfone 197. The treatment of 197
with BuLi in THF at low temperature induces a smooth isomerization into
O
O
BnO
HO
O
OH
TBSO
TBSO
OH
OH
HO
HO
OH
OH
HO
HO
(-)-175
Et 3 N
PhH, 20
o
C
(-)-Conduritol B
(+)-Conduritol F
(-)-193
1) H 2 /Pd
2) TBSOTf
94%
Scheme 32 The conversion of “naked sugars” into conduritols
Scheme 31 Synthesis of rac-illudin M
Synthesis of 7-Oxabicyclo[2.2.1]heptane and Derivatives
171