The enyne metathesis sequence could also be coupled with a subsequent crossmetathesis. As a demonstration of this, Plumet and coworkers exposed 235 to the
first generation Grubbs catalyst and allyl acetate to give bicyclic substrate 236 in
good yield (Scheme 63).
Liu and Rainier have reported ROM/CM reactions of 7-oxanorbornenes with
both neutral and electron-rich olefins to give the corresponding furans (Scheme 64)
[71]. Of particular interest in these studies was that the reaction was highly
regioselective giving 2,3,5-trisubstituted furans having the substituted alkene at C2
as illustrated by 239. While the majority of the substrates utilized a tosyl group on the
oxanorbornene, other substituents (ester, benzyloxymethyl) showed similar selectivity.
TMSO
OTMS
OR
1) Cl
OCH 3 271
OCH 3
TMSOTf (0.5 equiv), CH 2 Cl 2
2) DBU (2 equiv), THF
-78 °C to 20 °C
O
CO 2 R
H 3 CO
R 1
R 1 = alkyl, OMe, allyl
R = Me, Et, Bn, iPr
R 1
33%-97%
272 (dr >98:2)
270
Scheme 71 Silyl enol ethers as precursors of 2-alkylidene tetrahydrofurans by Langer et al. [77]
O
O
OtBu
NaH, n-BuLi, THF, 0 °C
O
Br
O
HO
O
68%
Ot-Bu
H 2 , Pd/C
MeOH, 20 °C
O
HO
O
Ot-Bu
87%
273
275
276 (dr = 10:1)
274
Scheme 72 Epibromohydrin approach to tetrahydrofurans by Langer et al. [78]
O
O
OCH3
LDA (2.3 equiv), THF
BrCH 2 CH 2 Cl
-78 °C to 20 °C
O
R
R
CO 2 CH 3
72%-86%
H 2 , Pd/C
CH 3 OH
O
R
CO 2 CH 3
89%-97%
264 (R = H, CH 3 )
265
266 (dr = 6:5)
Scheme 69 Nucleophilic substitution/cyclization strategy to tetrahydrofurans by Langer
et al. [76]
O
O
OEt
LDA (2.3 equiv), THF 0 °C;
-78 °C to 20 °C
O
CO 2 Et
75%
Br
Br
H 2 , Pd/C
EtOH
85%
O
CO 2 Et
267
268 (E/Z = 8:7)
269 (syn/anti = 9:2)
Scheme 70 Nucleophilic substitution/cyclization strategy to tetrahydrofurans by Langer
et al. [76]
Synthesis of Substituted Tetrahydrofurans
33