Biomedical Engineering Reference
In-Depth Information
TABLE 4.7 Synthesis of 6-Substituted 2-Pyrones
Entry
R
2
PCyp
3
(mol%)
Yield (%)
1
Ph
10
60
2
3-OMe-Ph
20
69
3
3-Cl-Ph
10
91
4
2-Naphthyl
30
66
5
2-Furyl
30
61
6
n
-Pr
30
34
O
R
2
cat. PCyp
3
CHCl
3
, 60
°
C
OO
CO
2
Et
+
R
2
H
4a
49
55
SCHEME 4.18
Synthesis of 6-substituted 2-pyrones.
electron-donating groups, including 2-naphthaldehyde and 2-furaldehyde, afforded
6-aryl-2-pyrones in yields greater than 60%. Although the yield was moderate when
using an aliphatic aldehyde, the reaction provided a valuable product—specifically,
6-
n
-propyl-2-pyrone (Table 4.7, entry 6), which possesses a sweet, creamy, coumarin-
like herbal flavor [80] and is used as an additive to alter the organoleptic properties
of tobacco [81-83]—in only a single step from a commercially available aldehyde
(Scheme 4.18 and Table 4.7).
When using methanol and
n
-butyllithium as additives in the presence of
trimethylphosphine, the annulations of allenoates with aldehydes produced the
dihydro-2-pyrones as products. The presence of methanol as a hydrogen-bond donor
induced the formation of dihydropyrones; the presence of
n
-butyllithium as an addi-
tive suppressed formation of the noncyclized product. Benzaldehydes possessing a
variety of electron-withdrawing substituents provided the desired dihydropyrones in
good yields. Aromatic substitution in the meta position was optimal, but substitution
at the ortho position, the most sterically susceptible site, was also tolerated. Similar
to the formation of dioxanes and pyrones, the use of more electron-rich aromatic
aldehydes rendered lower yields (Scheme 4.19 and Table 4.8). Nevertheless, the
convenience of this one-step synthesis of dihydro-2-pyrones from two commercially
cat. PMe
3
CH
2
Cl
2
,rt
Ar
O
O
O
•
2
Me
+
Ar
H
2eq.MeOH
1eq.
n
-BuLi
47b
OMe
49c
56
SCHEME 4.19
Synthesis of functionalized dihydro-2-pyrones.
