5984
J. Org. Chem. 1999, 64, 5984-5987
Novel Stereospecific Synthesis of 3-Chloroacrylate Esters via Palladium-Catalyzed Carbonylation of Terminal Acetylenes Jinheng Li, Huanfeng Jiang,* Aiqun Feng, and Lanqi Jia Guangzhou Institute of Chemistry, Chinese Academy of Sciences, P.O. Box 1122, Guangzhou 510650, China Received November 30, 1998
A simple and effective method for the highly regio- and stereospecific synthesis of (Z)-3-chloroacrylate esters is described. Using terminal acetylenes and primary, secondary, and tertiary aliphatic alcohols as substrates, the carbonylation reactions were carried out under carbon monoxide (1 atm) at room temperature in the presence of a catalytic amount of PdCl2 and 3 equiv of cupric chloride. Isolated yields of (Z)-3-chloroacrylate esters ranging from 30% to 72% were obtained. Our results show that the polarity of the alcohol-benzene solvent plays an important role in the stereochemistry of the products. Introduction 3-Chloroacrylate esters are valuable intermediates in organic synthesis1 and are known to exhibit some biological properties.2 There are many ways to synthesize 3-chloroacrylate esters,3 as a mixture of Z- and E-isomers, with the E-isomers predominating. The stereospecific synthesis of (Z)-3-chloroacrylate esters can be effected by the esterification of the corresponding acids.3b,4 It has also been reported that (Z)-3-chloroacrylate esters can be synthesized stereospecifically by the reaction of lithium chloride in acetic acid with actylenecarboxylates.5 Currently, the transition-metal-catalyzed carbonylation of terminal acetylenes may be one of the most useful strategies for the synthesis of (Z)-3-chloroacrylate esters. Heck has reported that 3-chloroacrylate esters (the E-isomers predominating) were observed as byproducts in the dicarbonylation of terminal acetylenes using PdCl2 and mercuric dichloride.6 A related synthesis of unsaturated β-chlorolactones (E-isomers) occurred when propargylic alcohols were mercurated and then carbonylated with a palladium catalyst.7 Unfortunately, the mercuration was successful only with relatively low molecular weight or symmetrically substituted propargylic alcohols. (1) (a) Modena, G. Acc. Chem. Res. 1971, 4, 73. (b) Patai, S.; Pappoport, Z. The Chemistry of Alkenes; Patai, S., Ed.; Interscience: London, 1964; Chapter 8. (c) Smith, A. B.; Kilenyl, S. N. Tetrahedron Lett. 1985, 26, 4419. (d) Bey, P.; Vevert, J. P. J. Org. Chem. 1980, 45, 3249. (e) Ege, G.; Franz, H. J. Heterocycl. Chem. 1982, 19, 1267. (f) Larock, R. C.; Narayanan, K.; Hershberger, S. S. J. Org. Chem. 1983, 48, 4377. (g) Zhang, C.; Lu, X. Synthesis 1996, 586. (h) Crousse, B.; Alami, M.; Linstrumelle, G. Tetrahedron Lett. 1995, 36, 4245. (i) Miura, M.; Okuro, K.; Hattori, A.; Nomura, M. J. Chem. Soc., Perkin Trans. 1 1989, 73. (2) (a) Vanghn, T. H. Union Carbide Corp., Belg. 1963, 631, 355; Chem. Abstr. 1964, 60, 11900h. (b) Herrett, R. A.; Kurtz, A. N. Science 1963, 141, 1192. (c) Kurtz, A. N.; Herret, R. A. Union Carbide Corp., Belg. 1963, 631, 083; Chem. Abstr. 1964, 60, 15071b. (3) (a) Winterfeldt, E. Angew. Chem., Int. Ed. Engl. 1967, 6, 423 and references cited therein. (b) Kultz, A. N.; Billups, W. E.; Greenlee, R. B.; Hamil, H. F.; Pace, W. T. J. Org. Chem. 1965, 30, 3141. (c) Wingfort Corp. Br. Pat. 1944, 564, 261; Chem. Abstr., 1946, 40, 3768.8 (4) Andersson, K. Chem. Scr. 1972, 2, 117. (5) (a) Ma, S.; Lu, X. J. Chem. Soc., Chem. Commun. 1990, 1643. (b) Ma, S.; Lu, X. Tetrahedron Lett. 1990, 31, 7653. (c) Ma, S.; Lu, X.; Li, Z. J. Org. Chem. 1992, 57, 709. (c) Lu, X.; Zhu, G.; Ma, S. Chin. J. Chem. 1993, 11, 267. (6) Heck, R. F. J. Am. Chem. Soc. 1972, 94, 2712. (7) Larock, R. F.; Riefling, B.; Fellows, C. A. J. Org. Chem. 1978, 43, 131.
Thus, new and effective stereospecific synthesis routes to (Z)-3-chloroacrylate esters are still of considerable interest to synthetic organic chemists. In this paper, we report that (Z)-3-chloroacrylate esters can be efficiently produced with high regio- and stereospecificity using terminal acetylenes, aliphatic alcohols, and carbon monoxide in the presence of a catalytic amount of PdCl2 and an excess of cupric chloride (eq 1).
Result and Discussion Preliminary results showed that the polarity of the solvent (alcohol-benzene) could affect the yield and Z/E ratio of 3a. Thus, we tried adding different amounts of methanol to vary the polarity of the solvent. A mixture of phenylacetylene (1a, 102 mg, 1 mmol) and methanol (2a, 0.04 mL, 1 mmol) reacted under CO (1 atm) in benzene (10 mL) at room temperature for 2 h in the presence of PdCl2 (10 mg, 0.056 mmol) and CuCl2 (269 mg, 2 mmol) (entry 1 in Table 1). The conversion of 1a was only 50%, and methyl 3-chloro-3-phenylacrylate (3a) was obtained in 20% GC yield (Z/E ) 84:16). The assignment of the stereochemistry of the product 3a is based upon the chemical shift of the olefinic proton (δ ) 6.53 in the 1H NMR spectra).3b,8 All of the results from (8) (a) Itoˆ, S.; Fugise, Y.; Sato, M. Tetrahedron Lett. 1969, 25, 691. (b) Ma, S.; Lu, X. J. Org. Chem. 1991, 56, 5120. (c) Minami, T.; Niki, I. J. Org. Chem. 1974, 39, 3236. (d) Tanaka, K.; Tamura, A. Chem. Lett. 1980, 595.
10.1021/jo982345u CCC: $18.00 © 1999 American Chemical Society Published on Web 07/14/1999
Stereospecific Synthesis of 3-Chloroacrylate Derivatives Table 1. Reaction of Phenylacetylene (1a) with MeOH (2a) under Carbon Dioxide in the Presence of PdCl2 and CuCl2a
entry
MeOH (mL)
CuCl2 (mmol)
yield of 3a, % (Z/E)b
1 2 3c 4 5 6 7e 8f
0.04 0.5 0.6 0.7 0.6 0.6 0.3 10
2 2 2 2 3 4 3 3
20 (84/16) 47 (98/2) 48 (98/2) 25 (only Z) 58 (only Z) (31%)d 57 (only Z) 53 (only Z) (30%)d trace
a Reaction conditions: 1a (1 mmol) and PdCl (0.056 mmol) in 2 C6H6 (10 mL) under CO (1 atm) at room temperature for 2 h. b Determined by GC analysis using an internal standard. c The conversion of 1a was 58%. d Isolated yields. e Reacted in 5 mL of C6H6. f Only methanol as solvent.
Table 2. Palladium-Catalyzed Carbonylation of Terminal Acetylenesa
entry
R1
R2
products
isolated yield (%)b
1 2 3 4 5 6 7 8 9 10 11
Ph Ph Ph Ph Ph C5H11 C5H11 C5H11 C5H11 C5H11 C5H11
Bu i-Pr s-Bu t-Bu t-pentyl Me Bu i-Pr s-Bu t-Bu t-pentyl
3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l
63 (77) 66 (82) 72 (90) 70 (86) 50 (58) 43 (60) 67 (81) 65 (81) 49 (60) 43 (49) 45 (55)
a Reaction conditions: 1 (1 mmol), 2 (0.6 mL), PdCl (0.056 2 mmol), and CuCl2 (3 mmol) in C6H6 (10 mL) under CO (1 atm) at b room temperature for 2 h. Isolated yields; GC yields are given in parentheses.
Table 1 indicate that the addition of 0.6 mL of methanol appears to be most effective (48% GC, Z/E ) 98/2) (entry 3). To examine this result more closely, we decreased the amount of methanol and benzene at the same ratio, which still resulted in a high yield (Table 1, entry 7). Therefore, the optimal ratio of methanol/benzene (v/v) is 0.6/10. Increasing the cupric chloride concentration has been reported by Heck6 to cause an increasing formation of 3-chloroacrylic esters, so the amount of cupric chloride was the next variable examined. Indeed, the amount of cupric chloride affected the yield of 3a in our experiments. By increasing the amount of cupric chloride from 2 to 3 mmol, the yields of 3a were increased from 48% to 58% (GC yields, only Z-isomer) (entries 3 and 5). When the amount of CuCl2 was increased to 4 mmol, the yield remained at 57% (entry 6). The above results encouraged us to use the palladium-catalyzed carbonylation for a general synthesis of (Z)-3-chloroacrylate esters. The results in Table 2 indicate that terminal acetylenes could be employed successfully in the carbonylation reaction, together with aliphatic alcohols, to give fair to
J. Org. Chem., Vol. 64, No. 16, 1999 5985 Scheme 1
good yields of (Z)-3-chloroacrylate esters.9 To our surprise, some sterically hindered aliphatic alcohols, such as s-BuOH (2d), t-BuOH (2e), and t-pentanol (2f), showed high activity in the reaction, indicating that this may be a simple and efficient method for the preparation of some sterically hindered esters. When terminal acetylenes reacted with the same alcohol, the activity of 1a is higher than that of 1b. It is of interest to note that an internal acetylene (4-octyne) did not afford 3-chloroacrylate esters under the same condition.10 When the experiments were carried out in a sealed system, the reaction was not clean and a mixture was formed. An open system may allow the majority of HCl gas generated in the reaction to be released into the air, thus delaying the acidification of the reaction mixture. In comparing the carbonylation products with the reaction conditions, we can come to some valuable conclusions. In polar solvents such as methanol, adding base (NaOAc)11 or acid (HCl)12 to the palladium-catalyzed carbonylation of acetylenes in the presence of cupric chloride afforded acetylenecarboxylates or unsaturated diesters, respectively. No 3-chloroacrylate esters were detected (Scheme 1). We found that the carbonylation reaction of 1a in MeOH without added acid or base afforded a mixtrue of unsaturated diesters and trace methyl (Z)-3-chloro-3-phenylacrylate (entry 8 in Table 1). Tsuji gave results similar to ours.11 When alcohol-benzene, a less polar solvent, was used in the reaction, 3-chloroacrylate esters were predominate in the products. In the presence of base (NaOAc), however, the reaction in the same solvent afforded (Z)unsaturated diesters with high stereoselectivity.13 All the results suggest that selectivity of the products may strongly depend on the polarity of solvent and the effect of added acid or base. It is interesting to hypothesize how the reaction proceeds mechanistically. The question regarding the first step of the reaction is whether chloropalladation of acetylenes or acylpalladation of acetylenes occurred first. Heck6 observed that the chloro esters were formed as byproducts in the 1-phenyl-1-propyne and 3,3-dimethyl1-butyne dicaroxylation reactions. He hypothesized that (9) Z- and E-isomers of such compounds may be separated by TLC on silica gel using light petroleum-ethyl ether (10:1) as eluant, but we did not detect any E-isomer. The chemical shifts of the olefinic proton in the 1H NMR (CDCl3) spectra for the alkyl (Z)-3-chlorophenylacrylates are all about δ ) 6.50 and for alkyl (Z)-3-chloro-2octenoates they are δ ) 5.90-6.00. GC analysis also showed that the products contained
