and 130 giving alcohols in high enantioselectivity with aromatic and
α,β-unsaturated aldehydes and with moderate enantioselectivity with aliphatic
aldehydes. The Koc ˇovsky ´ team utilized homoallylsilane 131 in condensation reactions with aldehydes to give substituted tetrahydrofurans 132 in both high yields
and diastereoselectivity.
The authors believe that the transformation outlined above proceeds via the
mechanism depicted in Scheme 35 where an oxonia-Cope rearrangement applied to
134 is followed by an intramolecular allylsilane addition to activated oxonium ion
135. The stereoselectivity in the generation of 132 is believed to be a result of chair
transition states in both the oxonia-Cope reaction and the allylsilane cyclization.
The Roush group has applied their [3+2]-cycloaddition to a number of natural
product syntheses (see [31] and [35, 87, 88]). One example is outlined in
Schemes 36 and 37 where they applied their chemistry to the total synthesis of
the annonaceous acetogenin natural product asimicin utilizing two [3+2]annulations to build the bis-tetrahydrofuran ring system [36]. To the first tetrahydrofuran ring, aldehyde 136 was subjected to a Brown allylboration using
diisopinocampheylborane 137 to efficiently give optically active allylsilane 138.
The generation of 2,5-trans-tetrahydrofuran 139 followed their previous results
using SnCl 4 as the Lewis acid.
O
H
OHC
H
8
OTBS
OTBDPS
9
TBSO
SiMe 2 Ph
SnCl 4 , CH 2 Cl 2 , 4 Å MS
0 °C
OTBDPS
OTBS
9
TBSO
O
O
8
TBSO
80%
OH
9
HO
O
O
8
HO
O
O
Asimicin
SiMe 2 Ph
PhMe 2 Si
PhMe 2 Si
142 (dr >20:1)
140
141
Scheme 37 [3+2]-Approach to Asimicin. Coupling and completion by Roush and Tinsley [36]
CuI, BrMg
OR
O
SiMe 2 Ph
PhMe 2 Si
38%
Et 2 O, -60 °C to -20 °C
TBSCl, imidazole
DMF, rt
85%
OHC
OBn
BF 3 •Et 2 O, 4 Å MS
CH 2 Cl 2 , -78 °C
68%
O
PhMe 2 Si
OBn
OTBS
TBAF, 4 Å MS, THF
65 °C, 1h
H 2 O 2 , TBAF, KHCO 3
MeOH, 65 °C, 4 h
64%
O
HO
OBn
OH
143
146
147
109
145 (R = TBS)
144 (R = H)
Scheme 38 Approach to the lytophilippines by Hodgson and Salik [32]
Synthesis of Substituted Tetrahydrofurans
17
α,β-unsaturated aldehydes and with moderate enantioselectivity with aliphatic
aldehydes. The Koc ˇovsky ´ team utilized homoallylsilane 131 in condensation reactions with aldehydes to give substituted tetrahydrofurans 132 in both high yields
and diastereoselectivity.
The authors believe that the transformation outlined above proceeds via the
mechanism depicted in Scheme 35 where an oxonia-Cope rearrangement applied to
134 is followed by an intramolecular allylsilane addition to activated oxonium ion
135. The stereoselectivity in the generation of 132 is believed to be a result of chair
transition states in both the oxonia-Cope reaction and the allylsilane cyclization.
The Roush group has applied their [3+2]-cycloaddition to a number of natural
product syntheses (see [31] and [35, 87, 88]). One example is outlined in
Schemes 36 and 37 where they applied their chemistry to the total synthesis of
the annonaceous acetogenin natural product asimicin utilizing two [3+2]annulations to build the bis-tetrahydrofuran ring system [36]. To the first tetrahydrofuran ring, aldehyde 136 was subjected to a Brown allylboration using
diisopinocampheylborane 137 to efficiently give optically active allylsilane 138.
The generation of 2,5-trans-tetrahydrofuran 139 followed their previous results
using SnCl 4 as the Lewis acid.
O
H
OHC
H
8
OTBS
OTBDPS
9
TBSO
SiMe 2 Ph
SnCl 4 , CH 2 Cl 2 , 4 Å MS
0 °C
OTBDPS
OTBS
9
TBSO
O
O
8
TBSO
80%
OH
9
HO
O
O
8
HO
O
O
Asimicin
SiMe 2 Ph
PhMe 2 Si
PhMe 2 Si
142 (dr >20:1)
140
141
Scheme 37 [3+2]-Approach to Asimicin. Coupling and completion by Roush and Tinsley [36]
CuI, BrMg
OR
O
SiMe 2 Ph
PhMe 2 Si
38%
Et 2 O, -60 °C to -20 °C
TBSCl, imidazole
DMF, rt
85%
OHC
OBn
BF 3 •Et 2 O, 4 Å MS
CH 2 Cl 2 , -78 °C
68%
O
PhMe 2 Si
OBn
OTBS
TBAF, 4 Å MS, THF
65 °C, 1h
H 2 O 2 , TBAF, KHCO 3
MeOH, 65 °C, 4 h
64%
O
HO
OBn
OH
143
146
147
109
145 (R = TBS)
144 (R = H)
Scheme 38 Approach to the lytophilippines by Hodgson and Salik [32]
Synthesis of Substituted Tetrahydrofurans
17