to avoid decomposition of the aldehyde during the [3+2]-cycloaddition, the authors
screened a number of Lewis acids and ultimately found that a mixture of
Yamamoto’s MAD catalyst and HNTf 2 was optimal.
Johnson and coworkers have also applied their cycloaddition chemistry to
the synthesis of (+)-virgatusin (Scheme 26) [26]. From enantiomerically pure
trans-cyclopropane 93, treatment with piperonal 94 in the presence of AlCl 3
gave 2,5-cis-tetrahydrofuran 95. Interesting was that 95 resulted from retention
of the stereochemistry on the cyclopropane which, in a similar fashion to the
Yang et al. observation (Scheme 19), is a consequence of reversible tetrahydrofuran
formation. As a result of this, the benzyl ester stereochemistry on the cyclopropane
was what ultimately dictated the C2 and C5 stereocenters.
In their total synthesis of (+)-isatisine A, Kerr and Karadeolian utilized a [3+2]cycloaddition strategy to the tetrahydrofuran (Scheme 27) [27]. The cycloaddition
between indole-2-carboxaldehyde 99 and vinylcyclopropane 100 was carried out
O
CO 2 CH 3 1) p-AcHNC 6 H 4 SO 2 N 3 , Et 3 N, CH 3 CN
2)
O
Cu, C 6 H 6 , 80 °C
N
t-Bu
t-Bu
2
O
CO 2 CH 3
H
OHC
OTMS
H3C
t-Bu
O
H 3 C
AlCH 3 (15 mol %)
2
HNTf 2 , CH 2 Cl 2 , -30 °C
O
O
H
R
OTMS
H 3 C
90 (R = CO 2 CH 3 )
76%
(dr = 11:1:0.6)
O
O
H
R
OTMS
H 3 C
Ru
NMes
MesN
Cl
Cl
O
ClCH 2 CH 2 Cl, 80 °C
70%
O
H
H
CH 3
O
H 3 C
H
H
CH 3
AcO
(+)-Polyanthellin A
71%
87
88
89
91 (10 mol %)
92
Scheme 25 Use of [3+2]-cycloadditions in the total synthesis of (+)-Polyanthellin A by Johnson
and Campbell [25]
BnO 2 C
CO 2 CH 3
CO 2 CH 3
OCH 3
OCH 3
AlCl 3 (15 mol %)
CH 2 Cl 2 , rt
80%
O
O
O
OCH 3
H 3 CO
BnO 2 C
CO 2 CH 3
CO 2 CH 3
95 (dr >20:1)
93
O
O
O
OCH 3
H 3 CO
H 3 CO
OCH 3
(+)-Virgatusin
via
O
O
O
OCH 3
H 3 CO
BnO 2 C
CO 2 CH 3
CO 2 CH 3
AlCl 3
O
O
O
OCH 3
H 3 CO
BnO 2 C
CO 2 CH 3
CO 2 CH 3
AlCl 3
O
O
O
OCH 3
H 3 CO
BnO 2 C
CO 2 CH 3
CO 2 CH 3
AlCl 3
95
96
97
98
O
O
OHC
94
Scheme 26 Use of [3+2]-cycloadditions to (+)-Virgatusin by Johnson et al. [26]
12
J.D. Rainier