As illustrated in Scheme 72, Langer et al. were also able to generate 2-alkylidene
tetrahydrofuran substrates from the alkylation of β-ketoesters with epibromohydrins (Scheme 72) [78]. Hydrogenation gave 2,5-cis-tetrahydrofuran 270 with
relatively high diastereocontrol.
Koskinen et al. have employed Pd-catalyzed π-allyl cyclizations to generate
tetrahydrofurans including the tetrahydrofuran present in the cytotoxic natural
product pachastrissamine (Scheme 73) [79]. From Z-allyl acetate 277 they were
able to generate tetrahydrofuran 278 as the major product in 59 % yield. Interestingly, they found the stereochemistry adjacent to the alkene to be an important
factor in the selectivity. The use of the syn-isomer 279 resulted in the generation of
tetrahydrofuran 280 in 81 % yield with 9:1 diastereoselectivity. Tetrahydrofuran
278 was subsequently transformed into pachastrissamine.
Gandon, Roulland, and coworkers have also used Pd-catalyzed π-allyl cyclizations
to generate tetrahydrofurans (Scheme 74) [80]. In a related fashion to Koskinen
et al. results, they found that product stereochemistry was dependent upon the relative
stereochemistry of the stereocenters on the allylic acetate. With cis-diol 281 they
isolated trans-tetrahydrofuran 282 as the major product, while the use of the
corresponding trans-diol 284 resulted in the generation of cis-tetrahydrofuran 285.
OHC
CHO
OPiv
OPiv
P
O
O
F 3 CH 2 CO
F 3 CH 2 CO
O
Ph
KHMDS, 18-crown-6, THF
– 85 °C
71%
CHO
OPiv
OPiv
295 (E/Z > 98:2; dr > 98:2)
LiBH 4 , iPrOH, THF, 0 °C
49%
Pd 2 (dba) 3 •CHCl 3 (5 mol %)
neocuproine (20 mol %)
THF, 65 °C
O
OPiv
79%
R*O 2 C
OPiv
OH
R*O 2 C
OPiv
R*O 2 C
289
294
296
297
Scheme 77 Pd-Catalyzed cyclizations to trans-tetrahydrofurans by Rein and Vares [82]
RCH 2 CHO +
CO 2 Et
O 2 N
N
H
Ph
Ph (5 mol %)
OTMS
PhCH 3
61-94%
OHC
R
NO 2
CO 2 Et
300 (dr = 87:13 to >98:2)
1) BH 3 •THF, CHCl 3
-13 °C
2) t-BuOK, THF
-55 °C
O
R
NO 2
CO 2 Et
301 (dr >90:10 to >95:5)
54-76%
(ee = 98 to >99%)
(ee = 97 to >99%)
298
299
Scheme 78 Tandem Michael additions to tetrahydrofurans by Ender et al. [83]
36
J.D. Rainier
tetrahydrofuran substrates from the alkylation of β-ketoesters with epibromohydrins (Scheme 72) [78]. Hydrogenation gave 2,5-cis-tetrahydrofuran 270 with
relatively high diastereocontrol.
Koskinen et al. have employed Pd-catalyzed π-allyl cyclizations to generate
tetrahydrofurans including the tetrahydrofuran present in the cytotoxic natural
product pachastrissamine (Scheme 73) [79]. From Z-allyl acetate 277 they were
able to generate tetrahydrofuran 278 as the major product in 59 % yield. Interestingly, they found the stereochemistry adjacent to the alkene to be an important
factor in the selectivity. The use of the syn-isomer 279 resulted in the generation of
tetrahydrofuran 280 in 81 % yield with 9:1 diastereoselectivity. Tetrahydrofuran
278 was subsequently transformed into pachastrissamine.
Gandon, Roulland, and coworkers have also used Pd-catalyzed π-allyl cyclizations
to generate tetrahydrofurans (Scheme 74) [80]. In a related fashion to Koskinen
et al. results, they found that product stereochemistry was dependent upon the relative
stereochemistry of the stereocenters on the allylic acetate. With cis-diol 281 they
isolated trans-tetrahydrofuran 282 as the major product, while the use of the
corresponding trans-diol 284 resulted in the generation of cis-tetrahydrofuran 285.
OHC
CHO
OPiv
OPiv
P
O
O
F 3 CH 2 CO
F 3 CH 2 CO
O
Ph
KHMDS, 18-crown-6, THF
– 85 °C
71%
CHO
OPiv
OPiv
295 (E/Z > 98:2; dr > 98:2)
LiBH 4 , iPrOH, THF, 0 °C
49%
Pd 2 (dba) 3 •CHCl 3 (5 mol %)
neocuproine (20 mol %)
THF, 65 °C
O
OPiv
79%
R*O 2 C
OPiv
OH
R*O 2 C
OPiv
R*O 2 C
289
294
296
297
Scheme 77 Pd-Catalyzed cyclizations to trans-tetrahydrofurans by Rein and Vares [82]
RCH 2 CHO +
CO 2 Et
O 2 N
N
H
Ph
Ph (5 mol %)
OTMS
PhCH 3
61-94%
OHC
R
NO 2
CO 2 Et
300 (dr = 87:13 to >98:2)
1) BH 3 •THF, CHCl 3
-13 °C
2) t-BuOK, THF
-55 °C
O
R
NO 2
CO 2 Et
301 (dr >90:10 to >95:5)
54-76%
(ee = 98 to >99%)
(ee = 97 to >99%)
298
299
Scheme 78 Tandem Michael additions to tetrahydrofurans by Ender et al. [83]
36
J.D. Rainier