Synthesis of new γ- and δ-lactones by acid cyclization of 2,4-diethylenic-diacids

Article abstract of DOI:10.1081/SCC-100000210

We have developed an easy synthesis for new γ- and δ-lactones. Acid-catalyzed cyclization of 2,4-diethylenic-diacids yields new γ or δ-lactones, depending on the substitution pattern of the unsaturated side chain.

Full text of DOI:10.1081/SCC-100000210

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SYNTHESIS OF NEW γ- AND δ-LACTONES BY ACID
CYCLIZATION OF 2,4-DIETHYLENIC-DIACIDS
Alain Valla a , Zo Andriamialisoa a , Frédéric Zentz , Virginie Prat , Alain Laurent &
Michel Giraud
a rue de l'Université , UMR 175, 6, Quimper, 29000, France
Published online: 16 Aug 2006.
To cite this article: Alain Valla , Zo Andriamialisoa , Frédéric Zentz , Virginie Prat , Alain Laurent & Michel Giraud (2001)
SYNTHESIS OF NEW γ- AND δ-LACTONES BY ACID CYCLIZATION OF 2,4-DIETHYLENIC-DIACIDS, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:2, 279-282, DOI: 10.1081/
SCC-100000210
To link to this article: http://dx.doi.org/10.1081/SCC-100000210
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SYNTHETIC COMMUNICATIONS, 31(2), 279–282 (2001)
SYNTHESIS OF NEW γ- AND δ-LACTONES
BY ACID CYCLIZATION OF
2,4-DIETHYLENIC-DIACIDS
Alain Valla,1,∗ Zo Andriamialisoa,2 Fre´de´ric Zentz,
Virginie Prat, Alain Laurent, and Michel Giraud
1UMR 175, 6, rue de l’Universite´ 29000 Quimper France.
Fax: 02 98 90 80 48.
2IUT, 2, rue de l’Universite´ 29334 Quimper Cedex France.
Fax: 02 98 90 85 44.
ABSTRACT
We have developed an easy synthesis for new γ - and δ-
lactones. Acid-catalyzed cyclization of 2,4-diethylenic-diacids
yields new γ or δ-lactones, depending on the substitution pattern
of the unsaturated side chain.
We recently reported the synthesis of a novel class of synthons, β-methylene-
aldehydes, and their use in the synthesis of 13 Z retinoic acids (1).
Because of the interplay between the stereochemistry of retinoids and their
biological activity, any method of synthesizing these compounds requires a stereo-
chemical control of the configurations of double bonds. We have studied the re-
activity of the E, E-ethylenic linkage by reinvestigating the behavior of a dienic
model in strong acid in order to extend the results previously reported (2,3).
∗ To whom correspondence should be addressed.
279
Copyright ꢀ 2001 by Marcel Dekker, Inc.
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C

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280
VALLA ET AL.
Scheme 1. a: X = H; b: X = CH3O; c: X = Cl.
Scheme 2.

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2,4-DIETHYLENIC-DIACIDS
281
Scheme 3.
The acid-catalyzed cyclization of 2-carboxy-5-aryl-2,4-pentadienoic acids
1 leads to the formation of γ -lactones 2 or δ-lactones 3 (4) (Scheme 1), depending
on the substitution pattern of the diethylenic side chain.
These reactions involve the initial formation of a pentadienyl cation. The
most stable form of this cation is probably the ‘W’ or ‘all-trans’ form, leading to
the δ-lactones 3 (R1 = CH3, R2 = H). There is a conformational change to a ‘U’
form when R1 = H and R2 = CH3. Cyclization of the latter to a cyclopentenyl
cation by electrocyclic reaction followed by internal lactonization gave the bicyclic
γ -lactones 2 (5–7) (Scheme 2).
The derivative 3 was shown unambiguously to have a δ-lactone structure
rather than a γ -lactone by base catalyzed decarboxylation to give the 2Z4E
monoacids 4 according to the following mechanism (8) (Scheme 3).
ACKNOWLEDGMENTS
We are indebted to Dr. Owen Parkes for improvement of our English.
REFERENCES AND NOTES
1. Giraud, M.; Valla, A.; Andriamialisoa, Z.; Potier, P. French Pat. 9415189,
1994.
2. Giraud, M.; Molho, D. Bull. Soc. Chim. Fr. 1970, 2651.
3. Rebuffat, S.; Giraud M.; Molho D. C.R. Acad. Sc. Paris 1977, 284, Ser C, 149.

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VALLA ET AL.
4. Giraud, M.; Molho, D. Bull. Mus. Nat. Hist. Nat. 1972, 101, 3.
5. A typical procedure for cyclization step is: l g of 1 was added to 20 cm3
concentrated sulphuric acid (R1 = H, R2 = CH3: 0◦C, 10 min.; R1 = CH3,
R2 = H: 0◦C, 4 h). The reaction mixture was poured over 100 g of ice and
extracted with diethyl ether. The organic layer was washed with water, dried
(Na2SO4), and evaporated under reduced pressure. The residue was purified by
recrystallization from ether (R1 = H, R2 = CH3) or by flash chromatography
eluting with 80/20 CH2Cl2/CH3OH and recrystallization from ether (R1 =
CH3, R2 = H). 2a. White crystals (75%) F: 152◦C. Anal. calc. For C13H12O4:
C, 67.23; H, 5.21; O, 27,56. Found: C, 67.08; H, 5.38; O, 27.66. IR (KBr) vCO
1765, 1720 cm−1. 1H NMR (400 MHz, CDCl3): 7.28 (m, 4H, H4,5,6,7); 4.13
(d, 1H, J = 3.3, H3); 3.78 (d, 1H, J = 3.3, H3a); 3.49 (d, 1H, J = 17.6, H8);
3.25 (d, 1H, J = 17.6, H8 ); 1.77 (s, 3H, CH3). 13C NMR: 170.8 (COOH);
ꢁ
==
168.8 (C O); 142.4, 140.5, (C3b,7a); 128.6, 128.0, 125.3, 125.2 (C4,5,6,7);
93.6 (C8a); 54.9, 54.7 (C3,3a); 45.2 (C8); 24.8 (CH3). 3a. White crystals (65%)
F: 104◦C. Anal. calc, For C13H12O4: C, 67.23; H, 5.21; O, 27,56. Found: C,
67.16; H, 5.25; O, 27.61. IR (KBr) vCO 1746, 1715 cm−1. 1H NMR (400 MHz,
CDCl3): 7.46–7.40 (m, 5H, H8,9,10,11); 5.49 (dd, 1H, J = 12.4, Jꢁ = 3.6, H5);
3.08 (dd, 1H, 1H J = 19.0, Jꢁ = 12.4, H6); 2.85 (dd, 1H, J = 19.1, Jꢁ = 3.6,
H6 ); 2.61 (s, 3H, CH3). 13C NMR: 172.8 (COOH); 167.6 (CO); 162.9 (C3);
ꢁ
136.2 (C4); 130.0 (C10); 129.3, 129.0 (C8,12 and C9,11); 77.8 (C5); 40.6 (C6);
23.8 (CH3).
6. Chiu, N.W.K.; Sorensen, T.S. Can. J. Chem. 1973, 51, 2776.
7. Howell, J.A.S.; O’Leary, P.J.; Yates, P.C.; Goldschmidt, Z.; Gottlieb, H.E.;
Hezroni-Langerman, D. Tetrahedron 1995, 51, 7231.
8. Deno, N.C.; Pittman, C.U., Jr.; Turner, J.O. J. Am. Chem. Soc. 1965, 87, 2153.
Received in the UK October 21, 1999

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