PbCl2/Ga bimetal redox system-mediated carbonndash;carbon bond formation reactions between carbonyl compounds and ethyl trichloroacetate and iodoacetonitrile

摘要

J. CHEM. soc. PERKIN TRANS. I 1995 PbCIJGa Bimetal Redox System-mediated Carbon-Carbon Bond Formation Reactions between Carbonyl Compounds and Ethyl Trichloroacetate and lodoacetonitrile Xiao-Lin Zhang,b Ying Han,' Wen-Tian Taob and Yao-Zeng Huang *** a Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Academia Sinica, 354 Fenglin Lu, Shanghai 200032, China Department of Chemistry, Wuhan University, Wuhan 430072, China In the presence of lead dichloride and a metallic gallium bimetal redox system, carbonyl compounds reacted with ethyl trichloroacetate and iodoacetonitrile to afford ethyl p-substituted a,a-dichloro- propionates and P-hydroxy nitriles, respectively, in moderate to excellent yields. Although, recently, there has been considerable interest in the synthetic application of bimetal redox systems, '-'gallium has received little attention compared with zinc and aluminium in this connection.Although there have been reports to the effect that Mg-HgC1, promotes the reaction of ethyl trichloroacetate with aldehydes to produce a non-halogenated P-hydroxy ester,' and that reductive addition of polyhalogenoalkanes to carbonyl compounds has been successfully achieved, the reaction of ethyl trichloroacetate with carbonyl compounds gives only a low yield of mixed products.5 It has also been reported the electroreduction of C13CC02Me, C12CHC02Me with alde- hydes yields methyl 0-substituted apdichloropropionate (9-47) and methyl P-substituted a-chloropropionate (32-73).9 OU L I Gan' Gao Scheme 1 A related group of compounds the P-hydroxy nitriles are important because they can undergo a variety of transform- ations.'O Of the many methods for generating nitrile anions," the Reformatsky-type reaction between bromoacetonitrile and carbonyl compounds in the presence of zinc represents one of the most useful methods for the preparation of P-hydroxy nitriles." Although, under standard conditions these are obtained only in moderate yield.13 Although slightly better yields are obtained with the pre-formed organozinc inter- mediate14 or by the use of other metals," the procedure is not simple.Herein, we report a novel synthesis of ethyl P-substituted a,a-dichloropropionate and P-hydroxy nitriles with the advantages of easy availability of the PbCl,/Ga bimetal redox system, simplicity of procedure, and moderate to excellent yields of product.Reductiue Addition of Ethyl Trichloroacetate to Carbonyl Compounds in a PbCl,/Ga Bimetal Redox System.-The reductive addition of ethyl trichloroacetate to the aldehyde la (R = 4-ClCaH4,R' = H) was performed as follows (Scheme 1). A mixture of la and 2 (ethyl trichloroacetate) (1 :2) in refluxing THF was treated with lead dichloride and gallium in slight excess (1.2 equiv.) for 6 h to afford the coupling product 3a in 72 yield. As shown in Table 1, satisfactory results were PbCyOa-THFRRCO + ICHamp;N reflux 4 5 R' 6 Scheme 2 Table 1 Effect of metal salts in the reductive addition of CI,CCO,Et to aldehyde la" Amount of Metal salts Time Yield Entry salts (mmol) (h) (Ib 1 2 4 3 5 6 7 PbCI, PbCI, None PbCI, SnCI,SnCI, ZnCI, 0.2 0.5 0 0.5 1 1 1 10 6 10 10 10 10 10 60.4 12 -(95)d -(90)c,d 48 -(85)c.d -(92) "Carried out with la (1 mmol), C13CC02Et(2 mmol) and Ga (1.2 mmol) in THF (4 an3)at reflux temperature.* Isolated yields based on aldehyde la. 'Without Ga. Aldehyde la was recovered. produced by use of a combination of lead dichloride with gallium (entries 1 and 2). The lead dichloride is indispensable, since in its absence no 3a (entry 4) was formed. Tin dichloride could be used in place of lead dichloride when double the amount was necessary, but the yield was only 48 (entry 5). Attempted use of zinc dichloride in place of lead dichloride failed to induce reductive addition of ethyl trichloroacetate to la.We applied the PbCl,/Ga bimetal redox system to the addition of ethyl trichloroacetate to a variety of carbonyl compounds 1, the experimental results of which are summarized in Table 2. The reaction of ethyl trichloroacetate with aldehydes la4 proceeded efficiently (entries 1-9), 1,Zaddition taking place with the a$-unsaturated aldehyde lf. In addition, the ketone li is reactive, affording 62 of the coupling product. Reductiue Addition of Iodoacetonitrile to Carbonyl Com- pounds in a PbClJGa Bimetal Redox System.-Under the same reactive conditions as for the reductive addition of ethyl trichloroacetate to carbonyl compounds, we carried out the PbCl,/Ga bimetal redox system promoted addition of iodo- acetonitrile to carbonyl compounds, to yield P-hydroxy nitriles (see Scheme 2).The reaction gave excellent yields of product and the experimental results are summarized in Table 3. The Table 2 Reductive addition of CI,CCOZEt to carbonyl compounds in a PbCI,/Ga bimetal system CI,CCO,Et Time Yield Entry Carbonyl compound (mmol) (h) 1 2 3 4 5 6 7 8 9 10 4-Chlorobenzaldehyde la 4-Chlorobenzaldehyde la 2-Bromobenzaldehyde lb 4-Fluorobenzaldehyde lc Benzaldehyde Id 4-Methylbenzaldehyde le trans-Cinnamaldehyde 11 Decanal lg Propionaldehyde lh Acetone li I 2 2 2 2 2 2 2 2 2 6 6 7 6 10 12 11 10 12 10 52 72 60 80 61 58 67 75 67 62 'Carried out with carbonyl compounds (1 mmol) and PbC1, (0.5 mmol) in THF (4 cm3) at reflux temperature.Isolated yield based on carbonyl compounds. Table 3 Synthesis of P-hydroxy nitriles 6" Time Product Entry Carbonyl compound 4 (h) yield () I 4-Chlorobenzaldehyde 4a 5 98 2 4-Fluorobenzaldehyde 4b 4 99 3 2-Bromobenzaldehyde 4c 4 99 4 Benzaldehyde 4d 6 92 5 4-Methylbenzaldehyde 4e 8 94 6 trans-Cinnamaldehyde 41 7 70 7 Decanal4g 8 82 8 Acetophenone 4h 8 80 9 4-Chlorobenzaldehyde 4a 5 55' 'Carried out with carbonyl compound (1 mmol), ICH,CN (2 mmol), Ga (1.2 mmol) and PbCI, (0.5 mmol) in THF (4 cm3) at reflux temperature. Isolated yield based on carbonyl compound. Without PbCI,. reaction of aromatic aldehydes 4a+ with iodoacetonitrile is very efficient with yields in the range 92-99. The a,P-unsaturated aldehyde 4f gave only 1,Zadduct whilst even the less reactive ketone 4h produced a good yield of product.Use of metal gallium in the absence of lead dichloride gave the coupling product in only 55 yield. No reaction occurred when chloroacetonitrile replaced iodoacetonitrile under the same conditions. Although the reaction mechanism of the PbCIJGa bimetal redox system has yet to be clarified, Scheme 1 illustrates a catalytic cycle which may be involved. In addition to the illustrated reaction process, a Pb-Ga alloy may be formed since lead(o) solvates into liquid gallium (m.p. 29.8 "C) in refluxing THF. In conclusion, we report a convenient, novel PbCl,/Ga bimetal redox system which promotes reactions of carbonyl compounds with ethyl trichloroacetate and with iodoaceto- nitrile, to yield ethyl 0-substituted a,amp;-dichloropropionates and 0-hydroxy nitriles in moderate to excellent yield.Further applications of the PbCI,/Ga bimetal redox system are now in progress in our group. Experimental M.p.s and b.p.s are uncorrected. M.p.s were measured on a capillary in a Tellon tube. 'H NMR spectra were determined in CDCl, on a Varian EM-360L (60 MHz) spectrometer with SiMe, as the internal standard. J-Values are given in Hz. IR spectra were recorded on a Shimadzu IR-440 instrument. Mass spectral data were obtained by electron ionization (EI) on a Finnigan 4021 spectrometer. All the reactions were J. CHEM.SOC. PERKIN TRANS. 1 1995 carried out under nitrogen. THF was dried and redistilled before use. Synthesis of Ethyl S-Substituted a.a-Dichloropropionates 3. General Procedure.-Into a mixture of PbCl, (139 mg, 0.5 mmol) and commercial gallium bar (83.7 mg, 1.2 mmol) in THF (4 cm-') were added the carbonyl compound (1 mmol) and ethyl trichloroacetate (383 mg, 2 mmol). The mixture was stirred under reflux until most of 1 had been consumed, after which it was diluted with ethyl acetate. The resulting mixture was filtered through a short column of silica gel and evaporated under reduced pressure. The residue was chromatographed on a silica gel plate or column (light petroleum-ethyl acetate 5 :1) to give the pure product. Ethyl 2,2-Dichloro-3-(4-chlorophenyl)-3-hydroxypropionate 3a (72), 6, 1.30 (3 H, t, J7), 3.50 (1 H, s, br), 4.30 (2 H, q, J 7), 5.45 (1 H, s) and 7.33 (4 H, s); v,,,(neat)/cm-' 3420vs, 1720vs, 1590m, 1490m, 1080m, 1060m and 860s.Ethyl 3-(2-Bromophenyl)-2,2-dichloro-3-hydroxypropionate 3b (60), 6, 1.30 (3 H, t, J 7), 3.36 (1 H, S, br), 4.40 (2 H, q, J 7), 6.16 (1 H, s) and 7.95 (4 H, m); v,,,(neat)/cm-l 3495vs, 1725vs, 1595m, 108Om, 1010m, 860s and 810s; m/z () 342 (M', 1),205(8), 187(94), 185(100), 171 (2), 156(18)and77(52) (Found: C, 38.4; H, 3.25. C,,Hl,BrCl,O, requires C, 38.63; H, 3.24). Ethyl 2,2-Dichloro-3-(4-~uorophenyl)-3-hydroxypropionate 3c (80), 6, 1.30 (3 H, t, J 7), 3.40 (1 H, s, br), 4.40 (2 H, q, J 7), 5.30 (1 H, s) and 7.25 (4 H, m); v,,,(neat)/cm-' 3500vs, 1760vs, 1610m, 1180m, 1040m and 860s; m/z () 281 (M', 5), 229 (12), 156 (20), 125 (loo), 109 (17) and 77 (18) (Found: C, 46.9; H, 3.7.CllH,lCl,FO, requires C, 47.00; H, 3.94). Ethyl 2,2-Dichloro-3-phenylpropionate 3d (61), b.p. 125 0C/0.5 mmHg, 6, 1.25 (3 H, t, J 7), 3.60 (1 H, s, br), 4.34 (2 H, q, J 7), 5.34 (1 H, s) and 7.40 (5 H, s); v,,,(neat)/cm-' 3420vs, 1720vs, 1590m, 1080m, lOlOm and 860s; m/z () 263 (M+,3,210 (12), 156 (8), 107 (63), 91 (23), 77 (43) and 71 (100) (Found: C, 50.25; H, 4.5. C,,H,,CI,O, requires C, 50.21; H, 4.60). Ethyl 2,2-Dichloro-3-hydroxy-3-(4-methylphenyl)propionate 3e (58), b.p. 14OoC/0.7 mmHg, bH 1.30 (3 H, t, J 7), 2.25 (3H,s),3.60(1 H,br),4.20(2H,q,J7),5.25(1H,s)and7.38 (4 H, m); v,,,(neat)/cm-' 3450vs, 1717vs, 1605m, 1070m, 1010m, and 860s; m/z () 278 (M + 1, 0.3), 225 (2), 156 (0.6), 121 (loo), 91 (21) and 77 (17) (Found: C, 52.3; H, 4.9.C,,H,,Cl,O, requires C, 52.00; H, 5.09). Ethyl2,2-Dichloro-3-hydroxy-5-phenylpent-4-enoate3f (67), b.p. 128 OC/O.4 mmHg, bH 1.25 (3 H, t, J 7), 3.40 (1 H, S, br), 4.42 (2 H, q, J 7), 4.80 (1 H, d), 6.1 5-6.90 (2 H, m) and 7.20 (5H, s); v,,,(neat)/cm-' 3450vs, 1750vs, 1660m, 1610m, 112Om, 1020m and 970m; m/z () 235 (M -HOCI, 7), 156 (3), 133 (27), 115 (53), 91 (33) and 71 (100) (Found: C, 54.0; H, 4.9. C13H,,C1203 requires C, 54.00; H, 4.88). Ethyl 2,2-Dichloro-3-hydroxydodecanoate3g (50), b.p. 148 'C/O3 mmHg,6,0.81 (3 H, t), 1.30 (3 H, t, J7), 1.70-1.30 (14H,m),3.50(1H,s,br),4.20(2H,q,J7)and4.40(3H,t); v,,,(neat)/cm-' 3480vs, 1760vs, 159Om, 1020m, 840m and 79Om; m/z () 313 (M', 2), 259 (2), 156 (100) and 147 (39) (Found: C, 53.6; H, 8.5.C14H,,C1,03 requires C, 53.67; H, 8.37). Ethyl 2,2-Dichloro-3-hydroxypentanoale3h (7573, b.p. 63 OC/O.4 mmHg) (1it.,l6 75 OC/O.8 mmHg), SH 0.95 (3 H, t), 1.25 (3 H, t, J 7), 1.40 (2 H, m), 2.80 (1 H, s, br), 4.05 (1 H, t) and 4.40 (2 H, q, J 7); v,,,(neat)/cm-' 3500vs, 1720s, 1600s, 1060s, 102Om and 870m. Ethyl 2,2-Dichloro-3-hydroxy-3-methylbutyrate3i (62), b.p. 53 "CjO.5 mmHg, lit.,16 43 "(70.2 mmHg, SH 1.30 (3 H, t, J 7), 1.95 (6 H, s), 3.16 (1 H, s, br) and 4.20 (2 H, q, J 7); J. CHEM. SOC. PERKIN TRANS. 1 1995 v,,,(neat)/cm-' 3500vs, 1720vs, 1600m, 1070m, 1020m and 870s.Synthesis of p-Hydroxy Nitriles 6.-3-(4-Chlorophenyl)-3-hydroxypropanenitrile 6a (98) 6, 2.68 (2 H, d, J6), 3.70 (1 H, s, br), 4.95 (1 H, t, J 6) and 7.30 (4 H, s); v,,,(neat)/cm-' 3500vs, 2240m and 830s. 3-Fluorophenyl-3-hydroxypropanenitrile 6b (9973, b.p. 142 "C/0.5 mmHg b.p. 15CL152 OC/l mmHg), (SH 2.48 (2 H, d, J6), 3.50 (1 H, s, br), 4.75 (1 H, t, 56)and 6.95 (4 H, m); v,,,(neat)/cm-' 3450vs, 2240m and 830s. 3-(2-Bromophenyl)-3-hydroxypropanenitrile6c (9973, m.p. 70-72"C,SH2.60(2H,d,J6),3.65(1 H,s,br),4.95(1 H,t,J6) and 7.35 (4 H, m); v,,,(KCl)/cm-' 3450vs, 2245m and 850s; m/z (x):227,225 (M*, 6, 7), 208 (0.3), 187 (84), 157 (19), 91 (3) and 77 (100) (Found: C, 47.9; H, 3.54. C,H,BrNO requires C, 47.81; H.3.57). 3-Hydroxy-3-phenylpropanenitrile 6d (92), b.p. 157-158 "C:'l.O mmHg (lit.,20 b.p. 154-155 OC/l mmHg), (5, 2.50 (2H,d,J6),3.66(1H,s,br),4.90(1H,t,J6)and7.25(5H,s); v,,,(neat)/cm-' 3400vs, 2240m, 1610w and 720s. 3-Hydroxy-3-(4-methylphenyl)propanenitrile 6e(94), b.p. 145 "C,'0.4 mmHg, 8, 2.40 (3 H, s), 2.67 (2 H, d, J6), 3.48 (1 H, s, br), 5.01 (1 H, t, J 6) and 7.35 (4 H, m); v,,,(neat)/cm-' 3450vs, 2240m and 830s. 3-Hydro.xy-5-phenylpent-4-enenitrile6f(70), b.p. 152 OCI0.6 mmHg (lit.,19 143 OCjO.5 mmHg), BH 2.50 (2 H, d, J 6), 3.60 (1 H, s, br), 4.60 (1 H, m), 6.2CL6.70 (2 H, m) and 7.30 (5 H, s); v,,,(neat)/cm-' 3420vs, 2240m, 1650s and 840s. 3-Hydro.xydodecanenitrile 6g (82), b.p. 130-132 "C/0.4 mmHg, BH 0.85 (3 H, t), 1.42 (14 H, m), 1.95 (2 H, m), 2.45 (2 H, d, J6), 3.65 (1 H, m) and 4.10 (1 H, s, br); v,,,(neat)/cm-' 3450vs, 3100wand2250m;m/z(): l97,195(M+,2,20), 179(4), 157 (2), 85 (13) and 43 (100) (Found: C, 73.5; H, 12.0; N, 7.35.CI2H,,NO requires C, 73.05; H, 11.75; N, 7.10). 3-Hydroxy-3-phenylbutanenitrile6h (go), b.p. 155-1 57 "Cj5 mmHg (lit.," b.p. 149-150 "C/4 mmHg), S, 1.60 (3 H, s), 2.65 (2 H, s), 3.40 (1 H, s, br) and 7.25 (5 H, s); v,,,(neat)/cm-' 3450vs, 2240m and 720s. 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M. Kaiser and C. R. Hause, J. Org. Chem., 1968,33, 3402. Paper 4/05784H Received 22nd September 1994 Accepted 27th September 1994