example of both of these concepts, Brown and coworkers discovered that polyenes
can undergo chemo- and stereoselective mono-tetrahydrofuran formation when the
amount of KMnO 4 is carefully controlled (Scheme 45) [48]. Thus, while the oxidation of triene 167 using 2.6 equivalents of KMnO 4 gave bicycle 168 in 35 % yield
after treatment with NaIO 4 , when 167 was treated with 1.8 equivalents of KMnO 4,
mono-tetrahydrofurans 169 and 170 were isolated in 52 % and 8 % yields,
respectively.
Further building on the chemoselectivity of the KMnO 4 process, Brown and
coworkers found that dienynes such as 171 undergo chemoselective and
stereoselective oxidative cyclizations to give tetrahydrofuran derivatives, for example,
172 and 173 in good yields (Scheme 46). In addition to this, in a subsequent transformation they found that the Z-alkene that results from the Lindlar reduction of 173
gives tetrahydrofuran derivative 174 after a second oxidative cyclization using Re 2 O 7
[49]. They propose that 174 comes from substrate-based stereocontrol, e.g., 175,
making the stereochemical outcome of the second tetrahydrofuran ring dependent
upon the outcome of the initial KMnO 4 reaction [50].
Brown and coworkers have applied their KMnO 4 oxidative cyclization technology
to the synthesis of several tetrahydrofuran-containing natural products. For example,
the treatment of sultam cyclization precursor 176 with KMnO 4 in acetone and
11
O
X
N
S
O
O
X =
KMnO 4
Acetone, HOAc (3:2)
75%
O
X
HO
H
H OH
10
177 (dr = 6:1)
O
1) NaBH 4 , THF, H 2 O (91%)
2) Bu 2 SnO, TsCl, TBAB (99%)
3) DBU, CH 2 Cl 2 (96%)
O
HO
H
H
10
O
O
HO
H
H
OH
10
O
O
(+)-cis-Solamin
176
178
Scheme 47 KMnO 4 approach to (+)-cis-solamin by Brown et al. [51]
O
X
8
Acetone/AcOH (4:1)
KMnO 4 (1.3 equiv)
O
H
H
C(O)X
OH
HO
57%
8
1) NaBH 4 , THF, H 2 O (94%)
2) (MeO) 2 CMe 2 , TsOH (92%)
AD-mix-α
O
H
H
HO
8 OH
HO
MeC(OMe) 3
CH 2 Cl 2 , 0 °C
K 2 CO 2 , CH 3 OH
O
H
H
O
H
H
HO
8
O
H
H
HO
8
O
O
O
O
OH
OH
94%
74%
O
H
H
O
H
H
HO
8
OH
O
O
9
Membrarollin
179
180
181
182
183
BF 3 •Et 2 O
Scheme 48 Synthesis of membrarollin by Brown et al. [48]
22
J.D. Rainier
can undergo chemo- and stereoselective mono-tetrahydrofuran formation when the
amount of KMnO 4 is carefully controlled (Scheme 45) [48]. Thus, while the oxidation of triene 167 using 2.6 equivalents of KMnO 4 gave bicycle 168 in 35 % yield
after treatment with NaIO 4 , when 167 was treated with 1.8 equivalents of KMnO 4,
mono-tetrahydrofurans 169 and 170 were isolated in 52 % and 8 % yields,
respectively.
Further building on the chemoselectivity of the KMnO 4 process, Brown and
coworkers found that dienynes such as 171 undergo chemoselective and
stereoselective oxidative cyclizations to give tetrahydrofuran derivatives, for example,
172 and 173 in good yields (Scheme 46). In addition to this, in a subsequent transformation they found that the Z-alkene that results from the Lindlar reduction of 173
gives tetrahydrofuran derivative 174 after a second oxidative cyclization using Re 2 O 7
[49]. They propose that 174 comes from substrate-based stereocontrol, e.g., 175,
making the stereochemical outcome of the second tetrahydrofuran ring dependent
upon the outcome of the initial KMnO 4 reaction [50].
Brown and coworkers have applied their KMnO 4 oxidative cyclization technology
to the synthesis of several tetrahydrofuran-containing natural products. For example,
the treatment of sultam cyclization precursor 176 with KMnO 4 in acetone and
11
O
X
N
S
O
O
X =
KMnO 4
Acetone, HOAc (3:2)
75%
O
X
HO
H
H OH
10
177 (dr = 6:1)
O
1) NaBH 4 , THF, H 2 O (91%)
2) Bu 2 SnO, TsCl, TBAB (99%)
3) DBU, CH 2 Cl 2 (96%)
O
HO
H
H
10
O
O
HO
H
H
OH
10
O
O
(+)-cis-Solamin
176
178
Scheme 47 KMnO 4 approach to (+)-cis-solamin by Brown et al. [51]
O
X
8
Acetone/AcOH (4:1)
KMnO 4 (1.3 equiv)
O
H
H
C(O)X
OH
HO
57%
8
1) NaBH 4 , THF, H 2 O (94%)
2) (MeO) 2 CMe 2 , TsOH (92%)
AD-mix-α
O
H
H
HO
8 OH
HO
MeC(OMe) 3
CH 2 Cl 2 , 0 °C
K 2 CO 2 , CH 3 OH
O
H
H
O
H
H
HO
8
O
H
H
HO
8
O
O
O
O
OH
OH
94%
74%
O
H
H
O
H
H
HO
8
OH
O
O
9
Membrarollin
179
180
181
182
183
BF 3 •Et 2 O
Scheme 48 Synthesis of membrarollin by Brown et al. [48]
22
J.D. Rainier