from 4. They also found that the generation of the oxocarbenium ion in the absence
of reducing agent led to equilibration at C-1 and to the all trans-diastereomer 6 after
a subsequent reduction step. Furan 6 was taken on to the lignan natural products
(+)-fragransin A and (+)-galbelgin.
Hong et al. were able to couple the epimerization sequence outlined in Scheme 2
with a Friedel–Crafts arylation to generate (+)-talaumidin precursor 8 (Scheme 3).
O
H 3 CO
BnO
OH
OTBS
OCH 3
BF 3 •Et 2 O, NaBH 3 CN
-78 °C
O
H 3 CO
BnO
OTBS
OCH 3
99%
O
H 3 CO
BnO
OTBS
OCH 3
1) BF 3 •Et 2 O, CH 2 Cl 2
-78 °C to -20 °C
2) BF 3 •Et 2 O, NaBH 3 CN
-78 °C
92%
(-)-Futokadsurin A
(-)-Verafuensin
(+)-Fragransin A
(+)-Galbelgin
4
5 (dr = 10:1)
6 (dr = 4:1)
Scheme 2 Synthesis of lignan natural products from lactol reductions by Hong et al. [7]
O
H 3 CO
BnO
OMe
O
O
BF 3 •Et 2 O, CH 2 Cl 2
-20 °C
O
H 3 CO
RO
O
O
8: R = Bn
7
(+)-Talaumidin: R = H
H 2 , Pd/C
EtOAc/EtOH (3:1)
rt
89%
98%
Scheme 3 Synthesis of (+)-talaumidin by Hong et al. [7]
N
O
O
O
O
O
H 3 CO
BnO
Li
TBSO
H 3 CO
O
H 3 CO
BnO
OH
OTBS
OCH 3
THF, -78 °C
70%
9
1 0
11
12
Scheme 4 Synthesis of lignan natural product precursors by Hong et al. [7]
O
BnO
Me
OAc
TMS
SnBr 4
93%
O
BnO
Me
(dr = 95:5)
via:
O
Me
H
BnO
inside attack
1
2
3
Scheme 1 Stereoelectronic model for tetrahydrofuran synthesis from oxocarbenium ion addition
by Woerpel et al. [6]
Synthesis of Substituted Tetrahydrofurans
3