Level 1 – Case 1
2
O
EtO
O
NaOEt
O
EtO
EtOH
2
3
acidic hydrogens
Knoevenagel
cyclization
1
O
O
Scheme 1.1
Unfortunately, exposure of 2 to sodium ethoxide in ethanol at 60°C did not
yield the expected cyclization product 3, but a mixture of compounds. The major
product was the ester 4 accompanied by two minor compounds that were identified as tricyclic alcohol 5 and tricyclic diketone 6 (this latter probably resulting
from the oxidation of alcohol 5) (Scheme 1.2).
1
O
EtO
O
NaOEt
EtOH
O
OEt
O
O
EtO
H OH
O
EtO
O
2
4 (62%)
5 (21%)
6 (8%)
O
O
O
Scheme 1.2
Suggest a reasonable explanation for the failure of the Knoevenagel cyclization
of compound 2. Propose a mechanism to justify how compounds 4 and 5 are obtained. To answer these questions use the information attained in the following
experiments.
Experimental Data
Exposure of the dioxolane-protected E-keto ester 7 to the Knoevenagel cyclization
conditions did not result in the formation of the ester 8 (Scheme 1.3).
1 The configuration of the alcohol in 5 was tentatively assigned as shown in Figure 1.1
upon NOESY experiments.
O
EtO
O
H OH
Figure 1.1