Organometallics 1983, 2, 598-600
598
Nickel-Catalyzed Synthesis of Arylacetic Esters from Arylzinc Chlorides and Ethyl Bromoacetate T. Klingstedt and T. Frejd" Organic Chemistry 1, Chemical Center, The University of Lund, S-220 07 Lund, Sweden Received September 1, 1982
Arylacetic ethyl esters are prepared from arylzinc chlorides and ethyl bromoacetates with a catalytic amount of bis(acetylacetonato)nickel(II)-phosphine complex.
Introduction Aromatic acetic acids and esters are an important class of compounds both per se' and for further transformations. Recently, two transition-metal-mediated syntheses of arylacetic esters were reported (eq 1 and 2), that can be formally described as a combination of a positive aryl species with a negative carbalkoxymethylene species. The Ar(hal) Ar(ha1)
+ LiCH,COO-t-Bu
'Ni"
ArCH,COO-t-Bu (Ar+ + -CH,COOR) (1)'
-+ - +
+ ZnBrCHzCOOEt
'Ni"
ArCH,COOEt (Ar+ ArZnCl
+ BrCH,COOEt
% yield of
entry
ArZnCl, Ar
1 2 3
Cd-4 o-CH,C,H, o-OCH,C,H, 2-fury1 2-thienyl 2-selenienyl
4 5 6 7
-CH,COOR) (2)3
'Ni"
ArCH,COOEt (Ar-
Table I. Yields of Reaction Products in the Reaction between Arylzinc Chlorides and Ethyl Bromoacetate Catalyzed by Ni(acac), Phosphine Complex
+CH2COOR) (3)
reaction in eq 1 was catalyzed by nickel(I1) bromide reduced by butyllithium but gave useful yields only with a stoichiometric amount of the nickel species., The Reformatsky-type coupling (eq 2) was catalytic in tetrakis(triphenylphosphine)nickel(O) but required HMPA as cosolvent for best results.3 Moreover, the nickel(0) catalyst had to be preformed since the Reformatsky reagent is not able to reduce Ni(I1) to Ni(0). The relatively high reaction temperature (45 "C) and long reaction time (3 h) make this reaction less attractive for the synthesis of substances such as allyl ethers that are sensitive to transition-metal catalysts. We now wish to report a third mild and simple alternative of arylacetic ester synthesis, in which an arylzinc halide is coupled with ethyl bromoacetate by the aid of a catalytic amount of bis(acetylacetonato)nickel(II)-phosphine complex. This reaction can be formalized as a combination of a negative aryl species and a positive carbethoxymethylene species (eq 3).
Results and Discussion The arylacetic esters were prepared by adding ethyl bromoacetate to a catalytic amount of the appropriate phosphine and Ni(acac)z followed by the arylzinc chloride! The results are shown in Table I. The only byproducts of importance were the homocoupled biaryls (13-15 %), (1) E.g., as nonsteroidal antiinflammatory agents: (a) Dunn, J. P.; Muchowski, J. M.; Nelson, P. H., J. Med. Chem. 1981, 24, 1097. (b) Brancaccio, G.; Larizza, A.; Lettieri, G., Ibid. 1981,24, 998. (c) Tamura, Y.; Yoshimoto, Y.; Tada, S.; Kunimoto, K.; Matsumara, S.; Murayama, M.; Shibata, Y.; Enomoto, H., Ibid. 1981, 24, 1006; 1981, 24, 43. (d) Lambelin, G.; Roba, J.; Gillet, C.; Buu-Hoi, N. P. Arzneim-Forsch. 1970, 20, 610. (2) Millard, A. B.; Rathke, M. W. J . Am. Chem. SOC.1977, 99,4833. (3) Fauvarque, J. F.; Jutand, A. J . Organomet. Chem. 1979, f77, 273; 1977,132, C17; 1981,209, 109. (4) These general reaction conditions were first described by: Negishi, E.; King, A. 0.; Okukado, N. J . Org. Chem. 1977, 42, 1821, for biaryl formation and are related to those of: Tamao, K.; Sumitani, K.; Kumada, M. J . Am. Chem. SOC.1972, 94, 4374, and Corriu, R. J. P.; Masse, J. P. J . Chem. Soc., Chem. Commun. 1972, 144, for the Kharasch reaction.
=
3-pyridyl
ArCH,COOEt (isolated/ GC ) a 59/77 60166
53/16 38/54C 45/63c
55/60' b
a The yields refer to the charged amount of ethyl bromoacetate. 0.01 equiv of triphenylphosphine and 0.01 equiv of Ni(acac), were used as catalyst at -5 "C.
0.05 equiv of cyclohexyldiphenylphosphineand 0.05 equiv of Ni(acac), were used as catalyst at + 20 "C.
which to a small extent were present in the arylzinc halide preparations! Thus, the major part, about 10% GC yield, must have been formed in the presence of the catalyst. At higher. reaction temperatures, the amount of biaryls increased. The byproducts were easily removed by flash chromatographyO6 Since it has been demonstrated that the catalytic species for other nickel(0)-catalyzed carbon-carbon bond formations does contain phosphine ligands associated with the nickel atom,7we repeated the coupling reaction with several different ligands. Ligandss with large cone angles (P(o-tol),, P(c-Hx),) or small cone angles (PEt3) and ligands with electron-withdrawing substituents (P(OEt),) gave low yields of 2-thienylacetic ester (
