generate enantiomerically pure 2,3-dideoxynucleoside analogs, Albert and
coworkers examined the asymmetric hydrogenation of 2,5-disubstituted furans
(Scheme 55) [62]. A survey of several different homogenous catalysts led them
to conclude that the steric bulk of the ligand was important both for activity and
selectivity. Their best result came from the use of the butiphane-type Rh-catalyst
208 which gave 3,4-dideoxynucleoside 207 in 98 % yield and in 72 % ee from the
reduction of furan 206.
6 Prins-Pinacol Cascades
The Overman group has studied and utilized Prins-pinacol cascades to generate
highly substituted tetrahydrofuran rings over the past 20 years [63]. An example
from the Overman group is given in Scheme 56 where acetal 209 (from the
O
O
H 3 C
iPr
H 3 C
TfOH (3 equiv)
CH 2 Cl 2 , -78 °C
90%
O
H 3 C
iPr
H
H 3 C
O
210 (dr >99:1)
O
OH
Me
Me
iPr
Prins
O
OH
Me
Me
iPr
Pinacol
209
211
212
Scheme 56 Prins-Pinacol cascade to substituted tetrahydrofurans by Overman et al. [64]
O
O
OTBDPS
SiMe 2 Ph
SnCl 4
CH 2 Cl 2 , -78 °C
89%
O
SiMe 2 Ph
O
OTBDPS
O
OH
HO
CHO
(–)-Citreoviral
213
214
Scheme 57 Prins-pinacol cascade to (–)-citreoviral by Overman et al. [65]
Scheme 58 Synthesis of spiro-fused tetrahydrofurans from Prins-pinacol cascades by Cho
et al. [66]
Synthesis of Substituted Tetrahydrofurans
27