Silver-Catalyzed One-Pot Synthesis of Arylnaphthalene Lactones Nicolas Eghbali, Jennifer Eddy, and Paul T. Anastas* Center for Green Chemistry and Green Engineering at Yale, Yale Chemistry Department, 225 Prospect Street, New HaVen, Connecticut 06520
[email protected] FIGURE 1. Structure of retrochinensin and daurinol.
ReceiVed June 05, 2008
Arylnaphthalene lignan lactones are part of a large family of phytoestrogen natural products which has received widespread interest in the last decades due to their biological activities.1 Specific examples include the known antiviral and antitumor agents daurinol and retrochinensin (Figure 1).2,3 Several synthetic methodologies have been developed to access the naphthalene core; this includes cross-coupling reactions and cycloadditions of 1,6-diynes to generate the C-ring.4 Most of
those syntheses still, however, rely on a traditional multistep chemistry and are lacking in terms of atom economy and/or efficiency.2,4 As an alternative approach, carbon dioxide has been recognized as a potential valuable C1 carbon source for the preparation of esters.5 In an effort to utilize CO2 and simplify the preparation of arylnaphthalene lignan lactones, we investigated a one-pot multicomponent coupling approach. Building on Inoue’s work,6 it was envisioned that the coupling between phenylacetylene, carbon dioxide, and 3-bromo-1-phenyl-1propyne would generate the corresponding 1,6-diyne which could further cyclize to the naphthalene core through a [2 + 2 + 2] cycloaddition.7 Initially, CuI was chosen as the catalyst for the desired transformation, namely the coupling between phenylacetylene, carbon dioxide, and 3-bromo-1-phenyl-1-propyne. The major compound isolated from this reaction was, however, the coupling product between phenylacetylene and 3-bromo-1-phenyl-1propyne. Carbon dioxide was not incorporated into the final product, even when the pressure was increased.8 Arylnaphthalene lactones were successfully prepared when the catalyst was switched to silver iodide. 4-phenylnaphtho[2,3c]furan-1(3H)-one 2a and 9-phenylnaphtho[2,3-c]furan-1(3H)one 3a were obtained in 41% and 25% yield, respectively (entries 3, Table 1). The ratio of regioisomers was slightly in favor of compound 2a. The major byproduct of the reaction was identified as the corresponding symmetrical carbonate.6 Silver complexes AgSbF6 and AgOAc were also effective to catalyze this reaction (entries 7 and 8, Table 1). Unexpectedly gold(I) iodide and gold(I) chloride, which have demonstrated promising catalytic activities for the coupling of phenylacetylene, carbon dioxide, and alkyl halides,9 failed to deliver the desired product. Monitoring the silver-catalyzed reaction by 1H NMR revealed that the coupling step was completed in less than 2 h while compound 1a slowly cyclized over 6 h. To verify whether AgI had any effect on the cyclization, pure samples of the 1,6-diyne 1a were heated in DMAc for 3 h. The results were the same in
(1) Westcott, N. D.; Muir, A. D. Phytochem. ReV. 2003, 2, 401. Suzuki, S.; Umezawa, T. J. Wood Sci. 2007, 53, 273. Clavel, T.; Dore, J.; Blaut, M. Nutr. Res. ReV. 2006, 19, 187. (2) Anastas, P. T.; Stevenson, R. J. Nat Prod. 1991, 54, 1687. Flanagan, S. R.; Harrowven, D. C.; Bradley, M. Tetrahedron 2002, 58, 5989. (3) Cow, C.; Leung, C.; Charlton, J. L Chem. Can. J. 2000, 78, 553. Gordaliza, M.; Garcia, P. A.; Miguel del Corral, J. M.; Castro, M. A.; GomezZurita, M. A. Toxicon 2004, 44, 441. (4) Klemm, L. H.; Gopinath, K. W.; HsuLee, D.; Kelly, F. W.; Trod, E.; McGuire, T. M. Tetrahderon 1966, 22, 1797. For recent reviews, see: Sellars, J. D.; Steel, P. G. Eur. J. Org. Chem. 2007, 3815. Ward, R. S. Tetrahedron 1990, 46, 5029.
(5) Aresta, M.; Dibenedetto, A Dalton Trans. 2007, 2975. Sakakura, T.; Choi, J.-C.; Yasuda, H. Chem. ReV. 2007, 107, 2365. Omae, I. Catal. Today 2006, 115, 33. (6) Fukue, Y.; Oi, S.; Inoue, Y. J. Chem. Soc., Chem. Commun. 1994, 2091. (7) For reviews on [2 + 2 + 2] cycloaddition, see: Chopade, P. R.; Louie, J. AdV. Synth. Catal. 2006, 348, 2307. Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741. Clayden, J.; Moran, W. J. Org. Biomol. Chem. 2007, 5, 1028. For a recent review on dehydro-Diels-Alder reaction: Wessig, P.; Mu¨ller, G. Chem. ReV. 2008, 108, 2051. (8) The coupling reaction (entry 1, Table 1) was also run in a pressure vessel under a higher carbon dioxide pressure (ca 10 atm); however, the results remain the same.
Arylnaphthalene lignan lactones are valuable natural products with promising anticancer and antiviral properties. In an effort to simplify their synthesis, we investigated a one-pot multicomponent coupling reaction between phenylacetylene, carbon dioxide, and 3-bromo-1-phenyl-1-propyne. After the corresponding 1,6-diyne was generated in situ, cyclization afforded the desired product. The level of regioselectivity was enhanced through the tuning of electronic properties. The use of cinnamyl bromide which led to the formation of a 1,6-enyne intermediate was also studied.
6932 J. Org. Chem. 2008, 73, 6932–6935
10.1021/jo801213m CCC: $40.75 2008 American Chemical Society Published on Web 08/06/2008
TABLE 1.
Preparation of Arylnaphthalene Lactones 2a and 3a
TABLE 2.
Synthesis of Various Arylnaphthalene Lactones Using the Silver-Catalyzed One-Pot Multi-component Coupling Reaction
productb a
entry
catalyst
time (h)
T (°C)
1 2 3 4 5 6 7 8 9 10
CuI CuBr AgI AgI AgI AgBr AgOAc AgSbF6 AuI AuCl
8 8 8 4 48 8 8 8 8 8
100 100 100 100 rt 100 100 100 100 100
1a
