Selective Reduction of the Exomethylene Group of α-Methylene γ- or δ-Lactones with CdCl2-Mg-MeOH-H2O

Article abstract of DOI:10.1039/a803981j

The strained exomethylene group of the α-methylene γ- or δ-lactone moiety in sesquiterpenoids can be selectively reduced with the CdCl₂-Mg-MeOH-H₂O reagent system.

Full text of DOI:10.1039/a803981j

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768 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 768±769$
Selective Reduction of the Exomethylene Group
of a-Methylene g- or d-Lactones with
CdCl2±Mg±MeOH±H2O$%
Asish K. Bhattacharya, Dharam C. Jain and Ram P. Sharma*
Phytochemical Technology Division, Central Institute of Medicinal and Aromatic Plants,
P.O. CIMAP, Lucknow-226 015, India
The strained exomethylene group of the ꢀ-methylene ꢁ- or ꢂ-lactone moiety in sesquiterpenoids can be selectively
reduced with the CdCl2±Mg±MeOH±H2O reagent system.
In continuation of our interest1 in metal±metal salt
Table 1 Reduction by CdCl2±Mg±MeOH±H2O
reductions and also to devise a cheap method for the
Yieldsb t/
reduction of the exomethylene group in arteannuin B 1,2
we studied its reaction with the CdCl2±Mg±MeOH±H2O
system. A mixture of two products was obtained which
were separated by preparative TLC. The more polar major
product, mp 180±182 8C, was identi®ed as the dihydro com-
pound 2 by direct comparison with an authentic sample.2
The less polar minor product, mp 128±130 8C, was identi®ed
as the methyl ester 3 by spectral data. In order to examine
the generality of this procedure, the reactions of other
substrates with CdCl2±Mg±MeOH±H2O were studied and
the results are given in Table 1.
Entry Substrate
Productsa
(%)
min
1
95:5
(98)
15
2
80:20 15
(88)
The reaction3 of d-lactone 4 with the above-mentioned
reagent combination furnished a mixture of C-11-epimers
(5 and 6) in the ratio of 4:1. The stereochemistry of the
C-11-methyl group was assigned on the basis of chemical
shift di€erence studies and coupling constant.4 Reduction of
compound2 7 with this reagent combination furnished only
one major product 8 in 90% yield.
3
4
(90)
15
The reduction of d-lactones3,5 (entries 7 and 8) also
furnished a mixture of C-11-epimers (13, 14) and (16, 17) in
the ratio of 1:4 and 4:1, respectively.
The substrates in entries 4 and 5 did not undergo any
reduction and the starting material was recovered quanti-
tatively. However, the substrate in entry
6 underwent
reduction to give dihydroarteannuin B 2 as the major pro-
duct.
From the experimental results discussed above, it appears
that the strained exomethylene group of the a-methylene
g- or d-lactone moiety undergoes smooth reduction with
CdCl2±Mg±MeOH±H2O. To account for the formation of
product 11 in the case of entry 6, it appears that the methyl
ester 3 is ®rst converted into the g-lactone, i.e. arteannuin B
1, which undergoes reduction and opening of the lactone
ring (see entry 1).
5
6
5:95
(90)
15
It is pertinent to mention here that the carbonyl function
is not reduced under these reaction conditions (see entry 3).6
7
20:80 15
(92)
Experimental
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded for thin ®lms on a Perkin
Elmer 1710 FT-IR spectrometer. 1H NMR spectra were recorded
in deuteriochloroform with tetramethylsilane as internal standard
on a Varian FT-80 (80 MHz) or a Bruker WM-400 (400 MHz)
spectrometer. Chemical shifts are expressed as d in ppm, and J
values in Hz. Most of the coupling constants were determined by
decoupling experiments. Mass spectra were recorded under electron
impact at 70 eV on a JEOL JMS D-100 spectrometer. TLC and
preparative TLC were performed on silica gel G (E. Merck, India).
8
80:20 15
(90)
aAll the product(s) gave satisfactory elemental analyses and
spectral data. bAll the yields refer to isolated chromatographically
pure compounds.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
%CIMAP Communication No.: 98±15J.
General Procedure.ÐTo a solution of the substrate (0.40 mmol)
in 3 ml of MeOH was added, with stirring, anhydrous CdCl2
(5.45 mmol) and Mg powder (32.91 mmol). Then H2O (111.11 mmol)

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J. CHEM. RESEARCH (S), 1998 769
was added dropwise to this reaction mixture over a period of
5 min when an instantaneous exothermic reaction took place with
the liberation of hydrogen. After 15 min, the reaction mixture
was diluted with 200 ml of CH2Cl2, washed with water and dried.
Evaporation of the solvent under reduced pressure produced a
residue which on puri®cation by preparative TLC (EtOAc±hexane,
1:4 or 1:9) furnished the product(s) characterized by spectral
analysis and direct comparison with authentic samples.
Received, 27th May 1998; Accepted, 4th August 1998
Paper E/8/03981J
References
1 C. Sarangi, A. Nayak, B. Nanda, N. B. Das and R. P. Sharma,
Tetrahedron Lett., 1995, 36, 7119.
Selected NMR data.ÐCompound 12: 1H NMR (80 MHz,
CDCl3): ꢂ 6.50 (dd, J 1.7 and 1.7, H-13a), 5.60 (dd, J 1.7 and
1.7, H-13b), 5.42 (br s, H-3), 5.12 (br s, H-5), 1.95 (s, OAc), 1.80
(s, H-15), 0.92 (d, J 7, H-14); compound 13: 1H NMR (400 MHz,
CDCl3): ꢂ 5.44 (br s, H-3), 5.18 (s, H-5), 2.84 (m, H-11), 2.09
(s, OAc), 1.80 (s, H-15), 1.22 (d, J 7, H-13), 0.95 (d, J 7, H-14).
Irradiation of the signal at ꢂ 1.22 (d, J 7, H-13) collapsed the
multiplet at ꢂ 2.84 (H-11) into a doublet (J 6.76); compound 14: 1H
NMR (400 MHz, CDCl3): ꢂ 5.55 (br s, H-3), 4.96 (s, H-5), 2.21
(m, H-11), 2.01 (s, OAc), 1.83 (s, H-15), 1.27 (d, J 7, H-13) 0.94
(d, J 7, H-14). Irradiation of the doublet (J 7) at ꢂ 1.27 (H-13)
collapsed the multiplet at ꢂ 2.21 (H-11) into a doublet (J 3.44).
2 A. K. Bhattacharya, D. C. Jain, R. P. Sharma, R. Roy and
A. T. McPhail, Tetrahedron, 1997, 53, 14975. Arteannuin B 1 is
the biogenetic precursor of artemisinin, a potent antimalarial
drug; e.g. S. S. Zaman and R. P. Sharma, Heterocycles, 1991, 32,
1593.
3 For preparatiaon of compounds 4 and 15, see A. K. Pathak,
D. C. Jain, R. S. Bhakuni, P. K. Choudhuri and R. P. Sharma,
J. Nat. Prod., 1994, 57, 1708.
4 C. R. Narayanan and N. K. Venkatasubramanian, J. Org. Chem.,
1968, 33, 3156.
5 Acetate 12 was prepared from compound 4 using BF3±Ac2O.
6 For comparison with Ni2B reduction, see±(a) C. A. Brown, Chem.
Commun., 1969, 952 and references cited therein; (b) C. A. Brown
and V. K. Akuja, J. Org. Chem., 1973, 38, 2226; (c) C. A. Brown,
J. Org. Chem., 1970, 35, 1900.
The authors are grateful to the Director, CIMAP for
kindly providing the necessary research facilities for this
work.