laboratories. For example, they demonstrated the ability to synthesize a wide
range of 2,5-cis-tetrahydrofurans in high diastereoselectivity from the reaction of
donor–acceptor cyclopropanes with aldehydes (Scheme 18) [16, 86]. The reaction
has been successful even with tetrasubstituted cyclopropanes resulting in the
generation of quaternary substituted tetrahydrofurans [17]. Through an analysis
of the scope of the reaction along with competition experiments, the authors
proposed an asynchronous mechanism whereby the reaction is initiated by
attack of the aldehyde on the cyclopropane as depicted by the 61–62 transformation [18].
Yang and coworkers have also examined cyclopropane [3+2]-cycloadditions to
give highly substituted tetrahydrofurans (Scheme 19) [19]. Interestingly, the AlCl 3 -
mediated cycloaddition of trans-cyclopropane 65 with electronically neutral or
electron-deficient aryl aldehydes led to a predominance of cis-tetrahydrofuran 64,
while the use of electron-rich aryl aldehydes resulted in the generation of the
corresponding trans-tetrahydrofurans 67. The authors demonstrated that the reaction was reversible and that the trans isomer resulted from the equilibration of the
cis isomer.
Ph
CO 2 CH 3
CO 2 CH 3
+ RCHO
O
Ph
R
CO 2 CH 3
CO 2 CH 3
Sn(OTf) 2 (5 mol %)
CH 2 Cl 2 , rt
(83-100%)
(dr = 1.6:1 to >100:1)
(ee = 34% to 99%)
H
O
R'
R
R
CO 2 CH 3
CO 2 CH 3
+ R'CHO
O
R
R'
CO 2 CH 3
CO 2 CH 3
Sn(OTf) 2 (5 mol %)
CH 2 Cl 2 , rt
83-100%
60 (dr = 1.6:1 to >100:1)
58
59
63
R
O
H 3 CO
O
OCH 3
SnX n
H
R'
O
H
R
O
H 3 CO
O
OCH 3
SnX n
H
O
H
R'
61
62
H
O
O OCH 3
OCH 3
Scheme 18 [3+2]-Cycloadditions of push–pull cyclopropanes by Johnson et al. [16, 17, 86]
Ph
CO 2 Et
CO 2 Et
+ RCHO
O
Ph
R
CO 2 Et
CO 2 Et
AlCl 3 (50 mol %)
CH 2 Cl 2 , 30 °C
47-81%
67 (dr= 65:10:4 to 82:2:0)
65
66
Ph
O
R = electron-rich aromatic
Ph
O
O
Ph
R
CO 2 Et
CO 2 Et
AlCl 3 (50 mol %)
CH 2 Cl 2 , 0 °C
37-88%
64 (dr = 75:16:1 to 90:0:0)
R = neutral and electron-poor aromatic
Ph
O
Scheme 19 Synthesis of tetrahydrofurans from trans-cyclopropanes by Yang et al. [19]
Synthesis of Substituted Tetrahydrofurans
9
range of 2,5-cis-tetrahydrofurans in high diastereoselectivity from the reaction of
donor–acceptor cyclopropanes with aldehydes (Scheme 18) [16, 86]. The reaction
has been successful even with tetrasubstituted cyclopropanes resulting in the
generation of quaternary substituted tetrahydrofurans [17]. Through an analysis
of the scope of the reaction along with competition experiments, the authors
proposed an asynchronous mechanism whereby the reaction is initiated by
attack of the aldehyde on the cyclopropane as depicted by the 61–62 transformation [18].
Yang and coworkers have also examined cyclopropane [3+2]-cycloadditions to
give highly substituted tetrahydrofurans (Scheme 19) [19]. Interestingly, the AlCl 3 -
mediated cycloaddition of trans-cyclopropane 65 with electronically neutral or
electron-deficient aryl aldehydes led to a predominance of cis-tetrahydrofuran 64,
while the use of electron-rich aryl aldehydes resulted in the generation of the
corresponding trans-tetrahydrofurans 67. The authors demonstrated that the reaction was reversible and that the trans isomer resulted from the equilibration of the
cis isomer.
Ph
CO 2 CH 3
CO 2 CH 3
+ RCHO
O
Ph
R
CO 2 CH 3
CO 2 CH 3
Sn(OTf) 2 (5 mol %)
CH 2 Cl 2 , rt
(83-100%)
(dr = 1.6:1 to >100:1)
(ee = 34% to 99%)
H
O
R'
R
R
CO 2 CH 3
CO 2 CH 3
+ R'CHO
O
R
R'
CO 2 CH 3
CO 2 CH 3
Sn(OTf) 2 (5 mol %)
CH 2 Cl 2 , rt
83-100%
60 (dr = 1.6:1 to >100:1)
58
59
63
R
O
H 3 CO
O
OCH 3
SnX n
H
R'
O
H
R
O
H 3 CO
O
OCH 3
SnX n
H
O
H
R'
61
62
H
O
O OCH 3
OCH 3
Scheme 18 [3+2]-Cycloadditions of push–pull cyclopropanes by Johnson et al. [16, 17, 86]
Ph
CO 2 Et
CO 2 Et
+ RCHO
O
Ph
R
CO 2 Et
CO 2 Et
AlCl 3 (50 mol %)
CH 2 Cl 2 , 30 °C
47-81%
67 (dr= 65:10:4 to 82:2:0)
65
66
Ph
O
R = electron-rich aromatic
Ph
O
O
Ph
R
CO 2 Et
CO 2 Et
AlCl 3 (50 mol %)
CH 2 Cl 2 , 0 °C
37-88%
64 (dr = 75:16:1 to 90:0:0)
R = neutral and electron-poor aromatic
Ph
O
Scheme 19 Synthesis of tetrahydrofurans from trans-cyclopropanes by Yang et al. [19]
Synthesis of Substituted Tetrahydrofurans
9