equivalent (Scheme 13). The latter was derived from 2,2-dimethylcyclohexa-1,3dione which is enolized into the corresponding triethylsilyl monoenol ether 93.
Asymmetric reduction of ketone 93 applies the Brown’s protocol [147]. Thus,
reaction of 93 with (À)-B-chlorodiisopinocampheylborane ((À)-DIPC) gives alcohol 94 with 95 % ee. Its iodination with N-iodosuccinimide (NIS) and intramolecular cyclization of the iodoalcohol intermediate 95 mediated by silver
triflate generates 7-oxanorbornanone 96. Its dimethylhydrazone 97 (mixture of
geometric stereoisomers) is used for the coupling with allyl tosylate 99. This key
intermediate is constructed in 12 steps starting from cyclohexenone 98. Hydrogen/
metal exchange of 7-oxanorbornanone hydrazone 97 with an excess of butyllithium
generates the bridgehead alkyllithium species that is converted into the
corresponding cuprate by reaction with CuBr/SMe 2 . The latter displaces the allylic
tosylate 99 giving 100 after hydrolysis of the dimethylhydrazone. The vinyl triflate
O
O
O
O
OTf
OAc
O
O T f
HO
OTf
O
O
COOM e
OAc
NIS
CH 2 Cl 2
AgOTf
O
O
OTBS
O
AcO
OTf
TsO
HO
O
I
O
NNMe 2
Me 2 NNH 2
CHO
OAc
O
O
COOMe
1) BuLi/THF, 0
o
C
then CuBr 2
. SMe 2
- 40
o C
2) + 99, - 40
o
C
65%
1) KHDMS
2) TIPSOTf
THF
90%
(-)-DIPCl
59%
100
CO (1 atm, 80
o
C)
Pd(OAc) 2
1,1'-bis(diphenylphosphino)ferrocene/Bu 3 N/DMF/MeOH
93
94 (ee = 95%)
95
2,6-Lutidine
CH 2 Cl 2
98
102
1) NaClO 2
NaH 2 PO 4
2-methyl-2-butene
t-BuOH/H 2 O, 0
o
C
2) LiI/2,4,6-collidine
120
o C,
then LiOH/THF, 60
o
C
3) H 2 SO 4 /H 2 O
Glycinoeclepin A
99
KHDMS: (Me 3 Si) 2 NK
TIPSOTf: (i Pr) 3 SiOSO 2 CF 3
9-BBN: 9-Borabicyclo[3.3.1]nonane
TBS: (t-Bu)Me 2 Si
TBAF: Bu 4 NF
NMO: N-Methylmorpholine
AcOH, EtOH
70
o
C
60% (based on 94)
96
97
3) AcOH/H 2 O, 130
o
C
101
87%
1) NMO/OsO 4
t-BuOH/H 2 O
THF, 0
o
C
2) NaIO 4 , 20
o
C
81%
95%
12 steps
O
NNMe 2
97
Scheme 13 Tanino et al. asymmetric total synthesis of glycinoeclepin A
Synthesis of 7-Oxabicyclo[2.2.1]heptane and Derivatives
157
Asymmetric reduction of ketone 93 applies the Brown’s protocol [147]. Thus,
reaction of 93 with (À)-B-chlorodiisopinocampheylborane ((À)-DIPC) gives alcohol 94 with 95 % ee. Its iodination with N-iodosuccinimide (NIS) and intramolecular cyclization of the iodoalcohol intermediate 95 mediated by silver
triflate generates 7-oxanorbornanone 96. Its dimethylhydrazone 97 (mixture of
geometric stereoisomers) is used for the coupling with allyl tosylate 99. This key
intermediate is constructed in 12 steps starting from cyclohexenone 98. Hydrogen/
metal exchange of 7-oxanorbornanone hydrazone 97 with an excess of butyllithium
generates the bridgehead alkyllithium species that is converted into the
corresponding cuprate by reaction with CuBr/SMe 2 . The latter displaces the allylic
tosylate 99 giving 100 after hydrolysis of the dimethylhydrazone. The vinyl triflate
O
O
O
O
OTf
OAc
O
O T f
HO
OTf
O
O
COOM e
OAc
NIS
CH 2 Cl 2
AgOTf
O
O
OTBS
O
AcO
OTf
TsO
HO
O
I
O
NNMe 2
Me 2 NNH 2
CHO
OAc
O
O
COOMe
1) BuLi/THF, 0
o
C
then CuBr 2
. SMe 2
- 40
o C
2) + 99, - 40
o
C
65%
1) KHDMS
2) TIPSOTf
THF
90%
(-)-DIPCl
59%
100
CO (1 atm, 80
o
C)
Pd(OAc) 2
1,1'-bis(diphenylphosphino)ferrocene/Bu 3 N/DMF/MeOH
93
94 (ee = 95%)
95
2,6-Lutidine
CH 2 Cl 2
98
102
1) NaClO 2
NaH 2 PO 4
2-methyl-2-butene
t-BuOH/H 2 O, 0
o
C
2) LiI/2,4,6-collidine
120
o C,
then LiOH/THF, 60
o
C
3) H 2 SO 4 /H 2 O
Glycinoeclepin A
99
KHDMS: (Me 3 Si) 2 NK
TIPSOTf: (i Pr) 3 SiOSO 2 CF 3
9-BBN: 9-Borabicyclo[3.3.1]nonane
TBS: (t-Bu)Me 2 Si
TBAF: Bu 4 NF
NMO: N-Methylmorpholine
AcOH, EtOH
70
o
C
60% (based on 94)
96
97
3) AcOH/H 2 O, 130
o
C
101
87%
1) NMO/OsO 4
t-BuOH/H 2 O
THF, 0
o
C
2) NaIO 4 , 20
o
C
81%
95%
12 steps
O
NNMe 2
97
Scheme 13 Tanino et al. asymmetric total synthesis of glycinoeclepin A
Synthesis of 7-Oxabicyclo[2.2.1]heptane and Derivatives
157