Gharpure and coworkers also found that the oxocarbenium ion from the cyclopropane opening reacts with carbon nucleophiles. C-Aryl furan 41 resulted from the use
of 1,3,5-trimethoxybenzene (40) as the nucleophile in the ring opening (Scheme 12).
Cyclopropyl furans 42 and 43 can also be induced to undergo ring opening distal
to the furan oxygen. For example, by employing free radical conditions, the
reduction of 42 or 43 resulted in 2,5-trans-furanones 44 and 45, respectively, via
cyclopropylcarbinyl radical ring opening and reduction (Scheme 13). Cyclopropylfuranones 42 and 43 came from the diazo decomposition of the corresponding
vinylogous carbonates 46 and 47, respectively (Scheme 14).
In a sequence that is the equivalent of an oxocarbenium-induced C–C bondforming reaction, McQuade and coworkers have used organic catalysts to carry out
the coupling of 2-hydroxy tetrahydrofuran 48 with methyl ketones 49 to give
2-alkyl furans (Scheme 15) [13]. Mechanistically the reaction is proposed to
proceed through the addition of a thiourea-stabilized enolate from the reaction of
49 with 51 to an iminium intermediate that comes from the condensation of 48 with
proline catalyst 50. Hydrolysis and Michael cyclization or displacement of the
ammonium ion subsequent to the Mannich reaction gives the observed product 52.
O
O
N 2
R
CO 2 Et
Cu(acac) 2 (10 mol %)
CH 2 Cl 2 , reflux
O
O
R
H
H
CO 2 Et
46, R = CH 3
47, R = CH 2 OBn
42, R = CH 3 (78%; dr > 19:1)
43, R = CH 2 OBn (70%; dr > 19:1)
Scheme 14 Synthesis of cyclopropyl furanones by Gharpure et al. [12]
O
OH
+
R
O
N
H
CO 2 H (10 mol %)
TBSO
N
H
S
N
H
CF 3
F 3 C
N
(25 mol %)
Dioxane, rt
O
O
R
(40-84%)
52 (ee = 0-48%)
48
49
50
51
Scheme 15 Use of organocatalytic aldol-Michael reactions to tetrahydrofurans by McQuade
et al. [13]
O
O
R
H
H
CO 2 Et
Bu 3 SnH, AIBN
PhH, reflux
O
O
R
CO 2 Et
42, R = CH 3
43, R = CH 2 OBn
44, R = CH 3 (93%)
45, R = CH 2 OBn (90%)
Scheme 13 Homolytic cyclopropane ring-opening strategy by Gharpure et al. [12]
Synthesis of Substituted Tetrahydrofurans
7
of 1,3,5-trimethoxybenzene (40) as the nucleophile in the ring opening (Scheme 12).
Cyclopropyl furans 42 and 43 can also be induced to undergo ring opening distal
to the furan oxygen. For example, by employing free radical conditions, the
reduction of 42 or 43 resulted in 2,5-trans-furanones 44 and 45, respectively, via
cyclopropylcarbinyl radical ring opening and reduction (Scheme 13). Cyclopropylfuranones 42 and 43 came from the diazo decomposition of the corresponding
vinylogous carbonates 46 and 47, respectively (Scheme 14).
In a sequence that is the equivalent of an oxocarbenium-induced C–C bondforming reaction, McQuade and coworkers have used organic catalysts to carry out
the coupling of 2-hydroxy tetrahydrofuran 48 with methyl ketones 49 to give
2-alkyl furans (Scheme 15) [13]. Mechanistically the reaction is proposed to
proceed through the addition of a thiourea-stabilized enolate from the reaction of
49 with 51 to an iminium intermediate that comes from the condensation of 48 with
proline catalyst 50. Hydrolysis and Michael cyclization or displacement of the
ammonium ion subsequent to the Mannich reaction gives the observed product 52.
O
O
N 2
R
CO 2 Et
Cu(acac) 2 (10 mol %)
CH 2 Cl 2 , reflux
O
O
R
H
H
CO 2 Et
46, R = CH 3
47, R = CH 2 OBn
42, R = CH 3 (78%; dr > 19:1)
43, R = CH 2 OBn (70%; dr > 19:1)
Scheme 14 Synthesis of cyclopropyl furanones by Gharpure et al. [12]
O
OH
+
R
O
N
H
CO 2 H (10 mol %)
TBSO
N
H
S
N
H
CF 3
F 3 C
N
(25 mol %)
Dioxane, rt
O
O
R
(40-84%)
52 (ee = 0-48%)
48
49
50
51
Scheme 15 Use of organocatalytic aldol-Michael reactions to tetrahydrofurans by McQuade
et al. [13]
O
O
R
H
H
CO 2 Et
Bu 3 SnH, AIBN
PhH, reflux
O
O
R
CO 2 Et
42, R = CH 3
43, R = CH 2 OBn
44, R = CH 3 (93%)
45, R = CH 2 OBn (90%)
Scheme 13 Homolytic cyclopropane ring-opening strategy by Gharpure et al. [12]
Synthesis of Substituted Tetrahydrofurans
7