Abstract
Introduction
Perezone (
1
), described in 1852 as the earliest natural product isolated in the New World, has been subject to a large amount of chemical, biological, and spectroscopic studies. Its cycloaddition reactions, including mechanistic studies to understand its transformation into α- and β-pipitzol as well as the stereoselectivity induction toward one of these isomers, are well known. Some years ago, intramolecular FeCl
3
-catalyzed [2+2] cycloaddition reactions were reported as a synthesis method of some natural products. We describe here the perezone (
1
) FeCl
3
-catalyzed cycloaddition products and their structural analysis based on
1
H NMR and vibrational circular dichroism (VCD) spectroscopy.
Methods
Perezone (
1
) was reacted in fluorobenzene in the presence of FeCl
3
at room temperature for 24 h. Following reaction completion, the products were isolated through silica gel column chromatography. Structural elucidation was achieved using
1
H,
13
C, and 2D NMR experiments, while the absolute configuration was unambiguously confirmed by VCD spectroscopy.
Results
The FeCl
3
-catalyzed transformation of perezone yielded α-pipitzol (
2
), β-pipitzol (
3
), α-isopipitzol (
4
), and a novel compound identified as (3a,7,8a)-tri-
epi
-α-isopipitzol (
5
) −the inverse epimer of α-isopipitzol− in a 38:41:14:7 ratio. While the absolute configuration of α-isopipitzol was confirmed using standard VCD protocols, the stereochemistry of its inverse epimer (
5
) was successfully established via the VCD chirality exciton approach.
Conclusion
The FeCl
3
-catalyzed cycloaddition of perezone yielded α-pipitzol (
2
), β-pipitzol (
3
), α-isopipitzol (
4
), and a novel inverse epimer of α-isopipitzol (
5
). Furthermore, the absolute configurations of compounds
4
and
5
were unambiguously confirmed via VCD as (3
R
,3a
S
,7
R
,8a
S
) and (3
R
,3a
R
,7
S
,8a
R
), respectively.