diethyl (E,E)-4-oxohepta-2,5-diene-1,7-dioate, 141, at 25
C under 5 kbar, giving a
single cycloadduct 142 in high yield. Using one equivalent of monoisopinocampheylborane ((+)-IpcBH 2 ), desymmetrization of 142 was realized by furnishing
alcohol (+)-143. Thus, in only two synthetic steps, the two planar compounds 140
and 141 have been converted into a polycyclic system (+)-143 made of a
7-oxanorbornanol and a 7-oxanorbornene moiety containing 11 stereogenic centers
[174] (see also [175]) (Scheme 23).
Another strategy to force furans to undergo Diels–Alder reactions is to limit the
cost of the entropy of condensation of intermolecular cycloadditions, making them
intramolecular [176–193]. This requires chemical attachment of the dienophile to
the furan moiety as illustrated with the following examples.
Condensation of furfural aldehyde with (R)-phenylglycinol gives an imine
which is reduced with NaBH 4 in isopropanol into amine 144 (Scheme 24). Temporary silylation of the primary alcoholic group of 144 as a trimethylsilyl ether and
subsequent acetylation of the amine moiety with 3,3-dimethylacryloyl chloride
O
H
O
H 2 N
Ph
OH
O
N
Ph
OH
H
Cl
O
O
N
Ph
OH
O
O
OR
O
OEt
O
O
N
Ph
HO
O
O
N H
O
OR
O
OEt
HO
+ O
OR
O
OEt
OH
1)
2) NaBH 4
91%
144
1) Me 3 SiCl/Py
2)
3) 5% HCl/H 2 O
87%
145
1) BuMgCl/Et 2 O
- 60
o
C
2) PhMe, reflux
69%
1) TsCl/Py/CH 2 Cl 2
2) DBU/MeCN
3) 5 M HCl/H 2 O
146
147
1) NaNO 2 /AcOH
Ac 2 O
2) KOH/EtOH
3) NaHCO 3 /H 2 O
1) Disiamylborane/THF
2) NaOH
H 2 O 2
148: R = H
149: R = (t-Bu)Me 2 Si
150 (76%)
151 (7%)
Scheme 24 Asymmetric intramolecular Diels–Alder reaction and regioselective hydroboration of
a 7-oxabicyclo[2.2.1]hept-5-ene derivative
O
O
E
E
O
O
O
O
E
H
H
E
O
O
O
E
H
H
E
OH
140 +
5 kbar
25
o
C
(+)-Ipc-BH 2
THF, - 25
o
C
E = COOEt
141
142
(+)-143 (ee = 78%)
95%
59%
Scheme 23 Eleven stereogenic centers in two steps from two symmetric compounds
164
A.J. Moreno-Vargas and P. Vogel