cycloadduct of furan and methyl acrylate (Scheme 38). Reduction of its ester
moiety into the corresponding primary alcohol and subsequent Swern oxidation
provides 7-oxabicyclo[2.2.1]hept-5-ene-2-endo-carbaldehyde. The addition of the
Grignard reagent 210 gives alcohol 211. After oxidation of 211 into the
corresponding ketone and oxime formation, compound 212 is obtained. The addition of PhSe radical to the alkene moiety of 212 generates a carbon-centered radical
that undergoes cyclization with the oxime and subsequent β-elimination of
2,4-dinitrophenoxy radical producing 213. Selenium/lithium exchange of 213
engenders a 7-oxanorborn-2-yl lithium species 214 that undergoes ethereal ring
opening, giving an intermediate cyclohexenol. Its imine moiety is converted into
allylcarbamate (alloc) 215. Alcohol oxidation and subsequent addition of
Me 3 SiCH 2 MgCl gives 216. The direct reduction of enamine 216 with NaBH 3 CN
under acidic conditions and subsequent Peterson olefination results in the formation
of a 1:1 mixture of exo- and endo-217. Then, in three steps, the 3-indolyl system is
installed in a classic Fischer indole synthesis that produces rac-peduncularine.
In 2008, and based on the SmI 2 -induced ethereal ring opening of 2-iodo-7-oxa
norbornane derivatives (Scheme 39), Carreira et al. presented a strategy for the
construction of the azabicyclononane skeleton of banyaside A and B isolated from
the cyanobacterium Nostoc sp. (IL-235) [269]. Both compounds inhibit the proteolytic activity of trypsin. The synthesis starts with the enantioselective Diels–Alder
N
O
O
Alloc
OH
TMS
N
O
O
Alloc
N
H
N
H
O
CHO
O
COOMe
O
O
O
HO
O
O
M g B r
O
N
O
O
O
NO 2
O 2 N
NaH +
O
O
HO
O
N
O
O
PhSe
O
N
O
O
N
OH
alloc
O
O
1)
2) Li
Li
AlH 4
3) (COCl) 2
DMSO, - 60
o
C
210
62% (3 steps)
211
3 steps
212
PhSeSePh, 50
o
C
93%
213
214
1) SO 3 /Py
Et 3 N/DMSO
2)TMSCH 2 MgCl
Et 2 O, - 78 to
20
o
C
62%
Naphthalene Li
THF, - 78
o
C
215
1) NaBH 3 CN/AcOH
CH 2 Cl 2 , 0 to 20
o
C
2) KH/THF, 20
o
C
56%
216
rac-Peduncularine
217
3 steps
25
o
C
AllylOCOCl
Py/CH 2 Cl 2
75%
Scheme 38 Synthesis of rac-peduncularine by Kitamura et al.
Synthesis of 7-Oxabicyclo[2.2.1]heptane and Derivatives
175
moiety into the corresponding primary alcohol and subsequent Swern oxidation
provides 7-oxabicyclo[2.2.1]hept-5-ene-2-endo-carbaldehyde. The addition of the
Grignard reagent 210 gives alcohol 211. After oxidation of 211 into the
corresponding ketone and oxime formation, compound 212 is obtained. The addition of PhSe radical to the alkene moiety of 212 generates a carbon-centered radical
that undergoes cyclization with the oxime and subsequent β-elimination of
2,4-dinitrophenoxy radical producing 213. Selenium/lithium exchange of 213
engenders a 7-oxanorborn-2-yl lithium species 214 that undergoes ethereal ring
opening, giving an intermediate cyclohexenol. Its imine moiety is converted into
allylcarbamate (alloc) 215. Alcohol oxidation and subsequent addition of
Me 3 SiCH 2 MgCl gives 216. The direct reduction of enamine 216 with NaBH 3 CN
under acidic conditions and subsequent Peterson olefination results in the formation
of a 1:1 mixture of exo- and endo-217. Then, in three steps, the 3-indolyl system is
installed in a classic Fischer indole synthesis that produces rac-peduncularine.
In 2008, and based on the SmI 2 -induced ethereal ring opening of 2-iodo-7-oxa
norbornane derivatives (Scheme 39), Carreira et al. presented a strategy for the
construction of the azabicyclononane skeleton of banyaside A and B isolated from
the cyanobacterium Nostoc sp. (IL-235) [269]. Both compounds inhibit the proteolytic activity of trypsin. The synthesis starts with the enantioselective Diels–Alder
N
O
O
Alloc
OH
TMS
N
O
O
Alloc
N
H
N
H
O
CHO
O
COOMe
O
O
O
HO
O
O
M g B r
O
N
O
O
O
NO 2
O 2 N
NaH +
O
O
HO
O
N
O
O
PhSe
O
N
O
O
N
OH
alloc
O
O
1)
2) Li
Li
AlH 4
3) (COCl) 2
DMSO, - 60
o
C
210
62% (3 steps)
211
3 steps
212
PhSeSePh, 50
o
C
93%
213
214
1) SO 3 /Py
Et 3 N/DMSO
2)TMSCH 2 MgCl
Et 2 O, - 78 to
20
o
C
62%
Naphthalene Li
THF, - 78
o
C
215
1) NaBH 3 CN/AcOH
CH 2 Cl 2 , 0 to 20
o
C
2) KH/THF, 20
o
C
56%
216
rac-Peduncularine
217
3 steps
25
o
C
AllylOCOCl
Py/CH 2 Cl 2
75%
Scheme 38 Synthesis of rac-peduncularine by Kitamura et al.
Synthesis of 7-Oxabicyclo[2.2.1]heptane and Derivatives
175