Hong et al. took a relatively straightforward approach to the lignan precursors
(Scheme 4). The absolute stereochemistry was established using oxazolidinone
9 and an Evans aldol reaction. Conversion to γ-lactone 10 was followed by the
addition of the appropriate aryl lithium 11 to give the requisite hemiketal 12.
Talaumidin precursor 7 came from the reduction of 10.
In a unique twist on the use of oxocarbenium reduction to generate tetrahydrofurans, Romo and Mitchell reported the generation of 2,5-cis- and 2,5-trans-tetrahydrofurans from the reductive cyclization of ketones having a pendant β-lactone
(Scheme 5) [8]. This reaction builds upon previously reported results from Mead
et al. and leads to the stereospecific synthesis of highly substituted tetrahydrofurans
[9]. For example, when anti-β-lactone 13 was subjected to TESOTf and excess Et 3 SiH,
they isolated 2,5-trans-tetrahydrofuran 14 in 82 % yield as a 14:1 mixture of diastereomers, while the corresponding syn-β-lactone 16 gave 2,5-cis-tetrahydrofuran 17
in 78 % yield as a >19:1 mixture of diastereomers. The stereochemical outcome of
these reactions is consistent with the Woerpel et al. model as depicted for the reduction
of 15 and 18.
In addition to the stereochemistry, Romo and coworkers found that the position
of the ether and the reaction conditions were important. When TiCl 4 or BF 3 ∙Et 2 O
were used instead of TESOTf in the reactions of 13 and 16, the corresponding furan
O
O
O
OBn
TESOTf (1.2 equiv)
Et 3 SiH (20 equiv), CH 2 Cl 2
O
H 3 C
H
OBn
CO 2 H
H
O
O
O
OBn
TESOTf (1.2 equiv)
Et 3 SiH (20 equiv), CH 2 Cl 2
O
H 3 C
H
OBn
CO 2 H
H
-78 °C to 0 °C
-78 °C to 0 °C
O
OBn
H
CO 2 TES
Et 3 Si H
H
O
Et 3 Si H
CO 2 TES
OBn
via:
via:
82%
78%
15
18
(dr >19:1)
17
(dr >19:1)
16
(dr >19:1)
13
(dr = 14:1)
14
Scheme 5 Keto-β-lactone cyclization to tetrahydrofurans by Romo and Mitchell [8]
O
O
O
TiCl 4 (1.2 equiv)
Et 3 SiH (20 equiv)
O
H 3 C
H
CO 2 H
H
20 (dr = 2:1)
19 (dr = 2:1)
O
O
O
TiCl 4 (1.2 equiv)
Et 3 SiH (20 equiv)
O
H 3 C
H
CO 2 H
H
22 (dr = 5:1)
21 (dr = 5:1)
TBSO
TBSO
TIPSO
OTBDPS
OTBDPS
TIPSO
CH 2 Cl 2 , -78 °C
CH 2 Cl 2 , -78 °C
O
H
CO 2 TES
Et 3 Si H
via:
OTBS
H
O
Et 3 Si H
CO 2 TES
via:
OTBS
OTBDPS
68%
55%
Scheme 6 Keto-β-lactone cyclizations to tetrahydrofurans by Romo and Mitchell [8]
4
J.D. Rainier
(Scheme 4). The absolute stereochemistry was established using oxazolidinone
9 and an Evans aldol reaction. Conversion to γ-lactone 10 was followed by the
addition of the appropriate aryl lithium 11 to give the requisite hemiketal 12.
Talaumidin precursor 7 came from the reduction of 10.
In a unique twist on the use of oxocarbenium reduction to generate tetrahydrofurans, Romo and Mitchell reported the generation of 2,5-cis- and 2,5-trans-tetrahydrofurans from the reductive cyclization of ketones having a pendant β-lactone
(Scheme 5) [8]. This reaction builds upon previously reported results from Mead
et al. and leads to the stereospecific synthesis of highly substituted tetrahydrofurans
[9]. For example, when anti-β-lactone 13 was subjected to TESOTf and excess Et 3 SiH,
they isolated 2,5-trans-tetrahydrofuran 14 in 82 % yield as a 14:1 mixture of diastereomers, while the corresponding syn-β-lactone 16 gave 2,5-cis-tetrahydrofuran 17
in 78 % yield as a >19:1 mixture of diastereomers. The stereochemical outcome of
these reactions is consistent with the Woerpel et al. model as depicted for the reduction
of 15 and 18.
In addition to the stereochemistry, Romo and coworkers found that the position
of the ether and the reaction conditions were important. When TiCl 4 or BF 3 ∙Et 2 O
were used instead of TESOTf in the reactions of 13 and 16, the corresponding furan
O
O
O
OBn
TESOTf (1.2 equiv)
Et 3 SiH (20 equiv), CH 2 Cl 2
O
H 3 C
H
OBn
CO 2 H
H
O
O
O
OBn
TESOTf (1.2 equiv)
Et 3 SiH (20 equiv), CH 2 Cl 2
O
H 3 C
H
OBn
CO 2 H
H
-78 °C to 0 °C
-78 °C to 0 °C
O
OBn
H
CO 2 TES
Et 3 Si H
H
O
Et 3 Si H
CO 2 TES
OBn
via:
via:
82%
78%
15
18
(dr >19:1)
17
(dr >19:1)
16
(dr >19:1)
13
(dr = 14:1)
14
Scheme 5 Keto-β-lactone cyclization to tetrahydrofurans by Romo and Mitchell [8]
O
O
O
TiCl 4 (1.2 equiv)
Et 3 SiH (20 equiv)
O
H 3 C
H
CO 2 H
H
20 (dr = 2:1)
19 (dr = 2:1)
O
O
O
TiCl 4 (1.2 equiv)
Et 3 SiH (20 equiv)
O
H 3 C
H
CO 2 H
H
22 (dr = 5:1)
21 (dr = 5:1)
TBSO
TBSO
TIPSO
OTBDPS
OTBDPS
TIPSO
CH 2 Cl 2 , -78 °C
CH 2 Cl 2 , -78 °C
O
H
CO 2 TES
Et 3 Si H
via:
OTBS
H
O
Et 3 Si H
CO 2 TES
via:
OTBS
OTBDPS
68%
55%
Scheme 6 Keto-β-lactone cyclizations to tetrahydrofurans by Romo and Mitchell [8]
4
J.D. Rainier