A simple and unambiguous synthesis of alpha;,alpha;- and alpha;,alpha;prime;-dihalogeno ketones

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1991 A Simple and Unambiguous Synthesis of a,a-and a,a'-Dihalogeno Ketones' Jose Barluenga,"*a Lujan Llavona,a Jose M. Concellon8 and Miguel Yusb a Departamento de Quimica Organometalica. Facultad de Quimica, Universidad de Oviedo, 33071 Oviedo, SpainDepartamento de Quimica Organica, Facultad de Ciencias, Universidad de Alicante, 03690 Alicante, Spain A convenient method for the unambiguous preparation of a,a'-dihalogeno ketones 3 from in situ- generated chloromethyllithium and x-chloro or a-bromo carboxylic acid esters 1 at -78 OC, is described. The unambiguous preparation of a,a,-dihalogeno ketones 7 by using in situ-generated dihalogenomethyllithium and carboxylic acid esters 5 at -78 "Cis also reported. The x,a-and a,a'-dihalogeno ketones are compounds of particular interest since they are highly functionalized mole- cules.Their high chemical reactivity enables them to undergo a wide variety of reactions and they are useful in organic synthesis. Thus, a,a'-dihalogeno ketones have been used, for instance, in the Favorskii rearrangement,2 in the generation of oxyallyl cation^,^ in the mono- and di-alkylation of ketone^,^ in the synthesis of 1-substituted cycl~propanols,~ in the prepar- ation of substituted thiocyclopropanols,6 and in the preparation of a-imino ketones and a-diimines.' On the other hand, a,u- dihalogeno ketones have been utilized, by example, in the Favorskii rearrangement,' in the preparation of but-2-en-4- olides,' for selective alkylation of ketones," and in the synthesis of cyclopropane derivatives.' ' However, the major limitation of dihalogeno ketones chemistry is that to our knowledge, there is no effective and simple method of synthesizing a variety of a,a'- dihalogeno ketones bearing either the same or different halogen atoms.12 On the other hand, although several syntheses of aliphatic x,a,-dihalogeno ketones have been reported '3*14the methods are not simple and most of them can only be used 14a3b3e for the preparation of a,a-dichloro ketones.Furthermore, the literature provides only a few examples ' of direct preparation l6 of a,a-dihalogeno ketones bearing two different halogen atoms. Recently we have described the utility of in situ-generated lithium carbenoids such as chloromethyllithium '' and dihalo- genomethyllithiums in organic synthesis. These results prompted us to study the possibility of obtaining a,a'- dihalogeno ketones from chloromethyllithium and ethyl a-halogenocarboxylates,' and a,=-dihalogeno ketones starting from dihalogenomethyllithium and carboxylic acid esters.A process of this type was described some time ago in the literature for the preparation of a,a-dihalogeno ketones; ' however, our methodology is simpler since the organolithium compound is generated in situ in the presence of the carboxylic acid ester. On the other hand, only two examples of the very interesting a-bromo-a-chloro ketones have been previously reported. In the present paper we report a simple, easy and rapid method for the unambiguous preparation of x,a-and a,a,'-dihalogeno ketones with the same or different halogen atoms (Hal = CI, Br).Results and Discussion Preparation of a,a'-Dihalogeno Ketones 3.-The reaction of different x-chloro or a-bromo carboxylic acid esters 1 with chloromethyllithium (1: 1.5 molar ratio) (generated in situ by treatment of chloroiodomet hane with met hy llit hium, at -78 "C),in the presence of lithium bromide at -78 OC, led to the corresponding intermediates 2, which after hydrolysis afforded the x,r'-dihalogeno ketones 3 (Scheme 1 and Table 1). Most of the isolated crude products 3 were pure ( 95 from X I RCH-CO2Et i, ii X OLi I1 -RCH-702Et iii, iv =- RCH-CCH2CI CH2CI 1 2 3 a; R = H, X = CI b;R = CI, X = CI c; R = Me,X = Br d; R = Me,X = CI e; R = Et, X = Br f; R = C5Hll, X = Br g; R = CsH13, X = CI Scheme 1 Reagents and conditions: i, 1.5 mol equiv. ClCH,l-LiBr; ii, 1.5 mol equiv.MeLi, -78 "C; iii HCl-Et,O, -78 "C; iv, aq. HC1 Table 1 a,'-Dihalogeno ketones 3 from a-halogeno carboxylic acid esters 1 a,a'-Dihalogeno ketone 3 Carboxylic acid ester 1 No. Yield ()" B.p./"C (mmHg) la 3a 60 172- 175 (760)b lb 3b 50 59-62 (lo)' lc 3c 64(36)d 68-73 (10) Id 3d 80 53- 57 le 3e 95 (69)s 84-88 (10) If 3f 75 32-35 (0.001) 1g 3g 80(34)d 79-82 (0.04) Isolated yield based on the initial amount of starting z-halogeno carboxylic acid ester 1. Lit.,20 b.p. 173 "C (760 mmHg). 'Lit.," 91-94deg;C (30 mmHg). dThe reaction was carried out in the absence of lithium bromide.Lit.," 55.5 "C (10 mmHg). Reaction time lh. NMR analysis) and did not need further purification. The intermediate 2 is stable under the reaction conditions due to the presence of the electronegative halogen substituents and it does not undergo elimination of the ethoxide group," so the addition of two molecules of chloromethyllithium to the ester 1 is not possible. However, the reaction of chloromethyllithium with 3-bromo-1-chloropentan-2-one3e gave the corresponding alcohol, 4 thus supporting the proposed mechanism (Scheme 2). OH i-iii I-C H3 C H 2C H Br-C(CHpCI)CH3CH2CHBr-CCH2CI 3e 4 Scheme2 Reagentsandconditions:i, 2mol equiv. ClCH,I-LiBr; ii, 3 mol equiv. MeLi, -78 "C; iii, aq.HCl, -78 OC In general, the yields of a,a'-dihalogeno ketones decrease in the absence of lithium bromide and when the reaction time is Table 2 a,a-Dihalogeno ketones 7 from carboxylic acid esters 5 ,a-Dihalogeno ketone 7 Carboxylic acid Dihalogeno ester 5 methane No. Yield ()" B.p./"C (mmHg) or R, 5a CH,Br, 7a-a 60 81-85 5a CH,BrCl 7a-b 64 (50)' 76-79 (10) 5a CH2Cl, 7a-c 71 (30)'(42)' 53-57 (lo), 5b CH,Br, 7b-a 75 68-72 (10)' 5b CH,BrCl 7b-b 61 (40)' 54-58 (10) 5b CH,CI, 7b-c 75 41-45 5c CH,Br, 7c-a 58 89-92 (10) 5c CH,BrCI 7~-b60 76-80 (10) 5c CH,CI, 7~-c64 59-63 (10)' 5d' CH,BrCl 7d-b 60 92-94 (O.l)k 5d' CH,Cl, 7d-c 66 128-132 (lo)' 5e' CH,BrCl 7e-b 60 0.44 In 5e' CH,Cl, 7e-c 62 78-82 (0.5) 5f CH,Br, 7f-a 77 108-1 12 (0.5) 5f CH,BrCI 7f-b 65 99-102 (0.5) 5f CH,Cl, 7f-c 55 66-70 (0.5) a Isolated yield based on the initial amount of starting carboxylic acid ester 5.Lit.,,, b.p. 88 "C (17 mmHg). 'The reaction was carried out at -30 "C. Reaction conditions: 2 h, -78 "C. 'Reaction conditions: 1 h, -78 "C. Lit.,I4'78-80 OC (43 mmHg). 'Lit.,23 70 "C (10 mmHg). Lit.,I4'70 "C (48 mmHg). Lit.,14'75 "C (30 mmHg). J Methyl ester was used as starting material. Lit.," 93 "C (0.1 mmHg). ' Lit.,24 82- 83 "C (1 mmHg). In Silica gel, hexane-Et,O (9.5:0.5). increased (see Table 1); in the last case dehalogenation compounds were obtained. Preparation of x,a-Dihalogeno Ketones 7.-Treatment of several carboxylic acid esters 5 with in situ-generated dihalo- genomethyllithium (1 :2 molar ratio) (see below) at -78 "C led to the corresponding intermediates 6, which did not undergo elimination of the ethoxide group under the reaction conditions and afforded, after acid hydrolysis, the expected a,a-dihalogeno ketones 7 (Scheme 3 and Table 2).OLi 0 it ii I iii II R-CO2Et =-R-COU R-CCHX'X20I CHX'X2 5 6 7 5 -7a;R = Pr" 6,7a -f; -a;X' = X2 = Br b;R = Pr' -b; X' = Br, X2= CI C;R = Bu' -c;X' = x2= CI d;R=Ph e; R = PhCH=CH f; R = PhCEC Scheme 3 Reagents and conditions: i, dihalogenomethane = CH,Br,, CH,BrCl, CH,Cl,; ii, R',NLi, -78 "C; iii, aq. HCl, -78 "C It is noteworthy that under these reaction conditions the dihalogeno ketone 7 is the only reaction product ( 95 from NMR analysis) and its isolation requires only removal of the solvent, without further purification.The dihalogenomethyl- lithium was generated in situ from dichloromethane or bromochloromethane and lithium dicyclohexylamide; in the case of dibromomethane the lithiation reaction was carried out with lithium diisopropylamide (LDA), since lithium dicyclo- hexylamide was not effective with this substrate. The reactions with dichloromethane and bromochloromethane can be also carried out at -30 "C (see Table 2); in these cases the yields are lower and it is necessary to purify the products by fractional distillation. The reaction times are short (ca. 0.5 h), the yields of J. CHEM. SOC. PERKIN TRANS. I 1991 dihalogeno ketones decreasing when the reaction times are longer, due to dehalogenation processes.In conclusion, this paper describes a convenient, rapid, simple and versatile procedure for the unambiguous synthesis of ,a-and a,a'-dihalogeno ketones starting from readily available materials. Experimental General.-IR spectra were determined with a Philips PV- 9716 and a Perkin-Elmer 1720-XFT spectrometer, as neat liquids. 'H and 13C NMR spectra were recorded on a Bruker AC-300 spectrometer, with SiMe, as internal standard; deuterio- chloroform was used as solvent. J Values are given in Hz. The purity of the volatile distilled or condensed products was determined with a GLC Varian Vista 6000 instrument equipped with an OV-101 Chromosorb column. MS (EI) were recorded with a Hewlett Packard 5987 A spectrometer.Elemental analysis was carried out with a Perkin-Elmer 240 Elemental Analyser. Starting a-halogeno carboxylic acid esters 1, chloro-iodomethane, dichloromethane, dibromomethane, bromo-chloromethane, methyllithium, butyllithium, dicyclohexylamine and LDA were of the best commercial grade available (Aldrich, Merck) and were used without further purification. Diethyl ether and tetrahydrofuran (THF) were successively dried with anhydrous calcium chloride, sodium sulphate, sodium and finally with potassium under reflux, and were distilled and stored under argon. All reactions were carried out under argon and all glassware was dried before use. Product 3a was commercially available (Aldrich) and was characterized by comparison with an authentic sample.(CAUTION! Most of the products 3 and 7 are lachrymatory and should be handled in a ventilated hood.) General Procedure for the Preparation of a,x'-Dihalogeno Ketones 3.-To a stirred solution of chloroiodomethane (0.43 cm3, 6 mmol), the x-halogeno carboxylic acid ethyl ester 1 (4 mmol), and lithium bromide (0.35 g, 4 mmol) in THF (10 cm3) was added an ethereal solution of methyllithium (1.5 mol dmP3; 6.4 mmol) during 5 min at -78 "C under nitrogen. The mixture was stirred for 20 min at this temperature, then the mixture was hydrolysed successively with a diethyl ether solution of HCI (5 mol dm-3; 2 cm3) and aq. HCl, and extracted with diethyl ether. The extract was dried (Na,SO,) and the solvents were removed (15 mmHg) to yield a residue that contained the expected ketone 3 of 95 purity (NMR, GLC).Compounds 3 can be purified by distillation at reduced pressure. 1,1,3-Trichloropropan-2-one3b v,,,(C=O)/cm-' 1740;6H4.6 (2 H, s, CH2Cl) and 6.2 (1 H, s, CHCI); 6, 42.9 (CH,Cl), 67.6 (CHCI) and 188.8 (C=O); m/z 166 (M+ + 6, 1), 164 (M+ + 4, l), 162 (M+ + 2,2), 160 (M+,2), 85 (14), 83 (19), 79 (31), 77 (100) and 49 (12). 3-Bromo- 1-chlorobutan-2-one 3c (Found: C, 25.7; H, 3.4. C,H,BrClO requires C, 25.91; H, 3.26); v,,,(C=O)/cm-' 1760; 6, 1.7 (3 H, d, J 6, Me), 4.6 (1 H, q, J 6, CHBr) and 4.4 (2 H, s, CH,CI); 6, 20.2 (Me), 45.1 (CH,Cl), 46.8 (CHBr) and 197.1 (C=O); m/~188 (M+ + 4,570,186 (M' + 2,23), 184 (M+, 17), 137 (94), 135 (loo), 109 (99), 107 (98), 79 (28), 77 (74), 56 (28), 49 (23) and 42 (18).1,3-Dichlorobutan-2-one 3d; v,,,(C=O)/cm-' 1760; SH 1.6 (3 H, d, J 7, Me), 4.4 (2 H, s, CH,Cl) and 4.6 (1 H, q, J 7, CHCI); 6, 19.7 (Me), 45.6 (CH,Cl), 55.5 (CHCI) and 196.7 (C=O); m/z 144 (M+ + 4,279, 142 (M' + 2,9), 140 (M+, 15), 93 (lo), 91 (35), 79 (34), 77 (loo), 65 (25), 63 (72), 49 (26) and 42 (1 8). 3-Bromo-1-chloropentan-2-one 3e (Found: C, 29.8; H, 4.2. C,H,BrClO requires C, 30.1 1; H, 4.04); v,,,(C=O)/cm-' 1760; 6H 1.0 (3 H, t, J 7, Me), 1.9-2.1 (2 H, m, CH,), 4.4 (2 H, d, J 7, J. CHEM. SOC. PERKIN TRANS. I 1991 CH,Cl) and 4.5 (1 H, t, J 7, CHBr); 6, 11.5 (Me), 26.2 (CH,), 45.5 (CH2C1), 51.1 (CHBr) and 195.5 (C=O); m/z 151 (M+ + 2 -CH,Cl,62), 149(M+ -CH,Cl,61), 123(94), 121 (loo), 119 (13), 79 (23), 77 (58), 70 (22), 55 (28), 51 (13), 49 (33), 42 (30), 41 (93) and 39 (42).3-Bromo-1 -chlorooctan-2-one 3f (Found: C, 39.5; H, 5.6. C,H ,,BrC10 requires C, 39.78; H, 5.84); v,,,(C=O)/cm-' 1760; 6,0.9-1.0 (3 H, m, Me), 1.3-1.5 (6 H, m, CH,,Me), 1.9-2.1 (2 H, m, CH2CHBr), 4.4 and 4.5 (2 H, 2 d, J 13, CH,Cl) and 4.6 (1 H, t, J 7, CHBr); 6, 13.6 (Me), 22.1, 26.6, 30.8 and 32.8 (CH,,), 45.2 (CH,Cl), 49.4 (CHBr) and 195.4 (C=O); m/z 244 (M+ + 4, 1), 242 (M+ + 2, l), 240 (M+, 1), 174 (13), 172 (51), 170 (40), 107 (ll), 105 (20), 83 (loo), 79 (ll), 77 (28), 69 (12), 55 (60), 43 (18), 41 (29) and 39 (13). 1,3-Dichlorononan-2-one 3g (Found: C, 49.9; H, 7.8.C,H16C120 requires C, 51.20; H, 7.64); v,,,(C=O)/cm-' 1750; 8, 0.9-1.0 (3 H, m, Me), 1.2-1.4 (8 H, m, CH,,Me), 1.9-2.0 (2 H, m, CH,CHCl), 4.5 (2 H, d, J 7, CH2C1) and 4.4-4.6 (1 H, m, CHCI); 6, 13.7 (Me), 22.2,25.6,28.3,31.2 and 33.2 (CH,,), 45.8 (CH,Cl), 60.7 (CHCl) and 196.4 (C=O); m/z 165 (Mf + 4 -CHZCI, l), 163 (M+ + 2 -CH2C1, l), 161 (M' -CH2C1, l), 130 (lo), 127 (65), 126 (loo), 105 (ll), 97 (56), 91 (15), 84 (18), 79 (20), 77 (54), 69 (14), 57 (15), 55 (70), 49 (17), 43 (27), 42 (13), 41 (30) and 39 (16). Synthesis of 3-Bromo- 1 -chloro-2-(chloromethy~pentan-2-01 4.-To a stirred solution of chloroiodomethane (0.36 cm3, 5 mmol), 3-bromo- 1-chloropentan-2-one 3e (0.50 g, 2.5 mmol), and lithium bromide (0.22 g, 2.5 mmol) in THF (10 cm3) was added an ethereal solution of methyllithium (1.5 mol dm-3; 12 mmol) during 5 min at -78 "C under nitrogen.The mixture was stirred for 10 min at this temperature, then the mixture was hydrolysed successively with a diethyl ether solution of HCl (5 mol dm-3; 2 cm3) and aq. HCl and extracted with diethyl ether. The extract was dried (Na,SO,), the solvents were removed (15 mmHg) and the resulting residue was distilled to afford the corresponding alcohol 4 (0.31 g, 50), b.p. 90-95 "C (20 mmHg) (Found: C, 28.6; H, 4.2. C6HllBrC~,0 requires C, 28.83; H, 4.43); v,,,(OH)/cm-' 3500; 6, 1.1 (3 H, t, J 8, Me), 1.8-2.1 (2 H, m, CH,Me), 2.5-2.6 (1 H, s, OH) and 3.5-4.3 (5 H, m, 2 x CH2CI and CHBr); 6, 12.7 (Me), 24.9 (CH,Me), 46.5 and 47.4 (2 x CH,Cl), 61.6 (CHBr) and 74.5 (COH); m/z 203 (M++ 4 -CH,Cl,lO), 201 (M+ + 2 -CH,CI, 38), 199 (M' -CH2C1,30), 131 (ll), 129 (67), 128 (15), 127 (loo), 126 (17), 121 (21), 119 (37), 93 (1 l), 91 (26), 79 (24), 77 (54), 63 (lo), 55 (12), 49 (14), 43 (lo), 41 (20) and 39 (17).General Procedure for the Preparation of a,z-Dihalogeno Ketones 7.-To a stirred solution of a dihalogenomethane (20 mmol) and a starting ethyl alkanoate 1 (10 mmol) in THF (20 cm3), was added a solution of lithium dicyclohexylamide (in the case of CH,Cl, and CH,BrCl) or LDA (in the case of CH,Br,) (20 mmol) in THF (20 cm3) during 10 min at -78 "C. The mixture was stirred for 20 min at the same temperature and the mixture was hydrolysed with aq.HCl (6 mol dm-3; 10 cm3). Then the solid was filtered off, the filtrate was extracted with Et,O, and the ethereal layer was dried (Na,SO,). The solvent was removed (15 mmHg) to yield a residue that contained the expected ketone 7 with 95 purity (NMR, GLC). Compounds 7 can be purified by distillation at reduced pressure. 1.1-Dibromopentan-2-one 7a-a; v,,,(C=O)/cm-' 1710; 6H 1.0 (3 H, t, J 7, Me), 1.7 (2 H, sextet, J 7, CH,Me), 2.9 (2 H, t, J 7, CH,C=O) and 5.8 (1 H, s, CH); 6, 13.2 (Me), 17.6 (CH,Me), 36.6(CH2C0),42.9(CH) and 196.5 (C=O);m/z 246 (M' + 4, 1), 244 (M' + 2, l), 242 (M+, l), 71 (loo), 43 (44), 41 (22) and 39 (10). 1-Brorno-1-chloropentan-2-one 7a-b (Found: C, 29.3; H, 4.2. C,H8BrC10 requires C, 30.1 1; H, 4.04); v,,,(C=O)/cm-' 1720; 299 6, 0.9 (3 H, t, J 7, Me), 1.6 (2 H, sextet, J 7, CH,Me), 2.7 (2 H, dt, J 7, 2, CH,C=O) and 5.9 (1 H, s, CH); 6, 13.2 (Me), 17.2 (CH,Me), 36.7 (CH,CO), 57.0 (CH) and 196.7 (C=O); m/z 200 (M+ + 2, 1), 71 (loo), 43 (73), 41 (36), and 39 (14).1,l-Dichloropentan-2-one 7a-c; v,,,(C=O)/cm-' 1720; 6,0.9 (3 H, t, J 7, Me), 1.6 (2 H, sextet, J 7, CH,Me), 2.7 (2 H, t, J 7, CH,) and 5.8 (1 H, s, CH); 6, 13.2 (Me), 17.0 (CH,Me), 36.7 (CH,CO), 69.7 (CH) and 196.8 (GO); m/z 158 (Mf + 4, 1), 156 (M+ + 2, 1), 154 (M', 1), 85 (16), 83 (24), 76 (17), 71 (83), 48 (lo), 43 (loo), 41 (47) and 39 (20). l,l-Dibromo-3-methylbutan-2-one7b-a; v,,,(C=O)/cm-' 1720; 6H1.2 (6 H, d, J 7, 2 x Me), 3.3 (1 H, septet, J 7, CH) and 5.9 (1 H, s, CHBr,); 6, 20.1 (2 x Me), 34.9 (CH), 41.9 (CHBr,) and 200.1 (GO); m/z 246 (M' + 4, 1), 244 (M++ 2, l), 242 (Mf, l), 71 (loo), 43 (79), 41 (36) and 39 (16).l-Bromo-l-chloro-3-methylbutan-2-one7b-b (Found: C, 29.6; H, 3.8.C,H,BrC10 requires C, 30.1 1; H,4.04); v,,,(C=O)/cm-' 1720; ZiH 1.2, 1.25 (6 H, 2 d, J 7, 2 x Me), 3.3 (1 H, septet, J 7, CH) and 6.0 (1 H, s, CHBrCl); 6c 19.5 and 20.0 (2 x Me), 35.0 (CH), 56.1 (CHBrCl) and 200.3 (C=O); m/z 202 (M+ + 4, 1), 200 (M+ + 2, l), 198 (Mf, l), 71 (loo), 43 (90), 41 (30) and 39 (10). 1,1-Dichloro-3-methylbutan-2-one7b-c; v,,,(C=O)/cm-' 1730; 6, 1.2 (6 H, d, J 7, 2 x Me), 3.2 (1 H, septet, J 7, CH) and 6.0 (1 H, s, CHC1,); 6c 19.4 (2 x Me), 35.0 (CH), 69.0 (CHC1,) and 200.3 (C=O); m/z 87 (M' + 4 -Pr'CO, 12), 85 (M + + 2 -Pr'CO, 64), 83 (M' -Pr'CO, loo), 78 (20), 76 (53), 71 (25), 55 (12), 51 (lo), 50 (33), 49 (19), 48 (79), 47 (27), 43 (39), 42 (lo), 41 (68), 40 (1 l), 39 (85), 38 (19) and 37 (12).l,l-Dibromo-4-methylpentan-2-one7c-a (Found: C, 27.6; H, 3.7. C6H,,Br,0 requires C, 27.94; H, 3.91); v,,,(C=O)/cm-' 1720; 6, 0.9 (6 H, d, J 7, 2 x Me), 2.2 (1 H, nonet, J 7, CH), 2.7 (2 H, d, J 7, CH,) and 5.7 (1 H, s, CHBr,); 6, 22.1 (2 x Me), 24.4 (CH), 43.3 (CHBr,), 43.5 (CH,) and 195.8 (C=O); m/z 260 (M' + 4, 1), 258 (M' + 2, l), 256 (M +, l), 199 (48), 85 (loo), 57 (59), 43 (15), 41 (36) and 39 (16). 1-Bromo-l-chloro-4-methylpentan-2-one7c-b (Found: C, 33.9; H, 4.7 C6H1oBrClO requires C, 33.75; H, 4.72'1;); v,,,(C=O)/ cm-' 1720 aH 0.9, 0.95 (6 H, 2 d, J 7, 2 x Me), 2.1 (1 H, nonet, J 7, CH), 2.7 (2 H, d, J 7, CH,) and 5.8 (1 H, s, CHBrCl); 6, 22.0 and 22.1 (2 x Me), 24.2 (CH), 43.6 (CH,), 57.2(CHBrCl)and196.1(C=O);m/z131(M+ + 4 -Pr'CH,CO, 2), 129 (M' + 2 -Pr'CH,CO, 6), 127 (M+ -Pr'CH,CO, 4), 85 (M+ -CHBrCl, loo), 57 (93), 43 (23), 41 (40) and 39 (13).1,l-Dichloro-4-methylpentan-2-one7c-c; v,,,(C=O)/cm-' 1730; 8, 1.0 (6 H, d, J 7, 2 x Me), 2.2 (1 H, nonet, J 7, CH), 2.6 (2 H, d, J 7, CH,) and 5.8 (1 H, s, CHCI,); 6, 21.7 (2 x Me), 23.8 (CH), 43.2 (CH,), 69.6 (CHCl,) and 195.8 (C=O); m/z 87 (M' + 4 -Pr'CH,CO, 11), 85 (M+ + 2 -Pr'CH,CO, 79), 83 (M' -Pr'CH,CO, loo), 78 (ll), 76 (31), 57 (41), 50 (18), 48 (44), 47 (16), 43 (24), 42 (54), 41 (92), 40 (14), 39 (90) and 38 (14). a-Bromo-x-chloroacetophenone 7d-b;v,,,/cm-' 3060 (CXH) and 1690 (C=O); 6H 6.8 (1 H, s, CHClBr), 7.5 (2 H, t J 7, CH,), 7.6 (1 H, t, J 7, CH,), and 8.0 (2 H, m, CH,); 6, 54.1 (CHBrCl), 128.7, 129.4, 131.0 and 134.3 (C,H,) and 185.8 (C=O); mjz 234 (Mf + 2, l), 232 (M+, I), 105 (loo), 77 (37) and 51 (12).,a-Dichloroacetophenone7d-c; v,,,jcrn-' 3060 (C=CH) and 1700 (GO); 6, 6.8 (1 H, S, CHCI,), 7.47.6 (3 H, m, 2 CH,, CH,,), and 8.0 (2 H, d, J 8 CH,); 6, 67.6 (CHCl,), 128.7, 129.4, 13 1 .O and 134.4 (C6H5) and 185.6 (C=O); rn/z 125 (1 673, 105 (M+ -CHC1,,72), 89 (12), 85 (Mf + 2 -C~HSCO,38), 83 (M+ -C~HC,CO, 56), 78 (12), 77 (loo), 76 (25), 75 (12), 74 (24), 63 (IS), 62 (13), 51 (71), 50 (68), 49 (14), 48 (53), 47 (16), 39 (11) and 38 (12).(E)-1 -Bromo- 1 -chloro-4-phenylbut-3-en-2-one7e-b (Found: C, 46.0; H, 2.9. C1oHgBrC10 requires C, 46.26; H, 3.11); v,,,(C=CH)/cm-' 3060 and 3020and 1690(C=O);tiH6.0(1 H, s, CHClBr), 7.2 (1 H, d, J 16,CHSHCO), 7.4-7.7 (5 H, m Ph) and 7.8 (1 H, d, J 16, CHSHCO); 6, 56.9 (CHClBr), 117.6 (CH=mCO), 128.7, 128.9, 131.3 and 133.7 (C,H,), 147.6 (CH=CHCO) and 185.5 (C=O); m/z 262 (M++ 4, 1), 260 (M+ + 2, l), 258 (Mf, l), 132 (lo), 131 (loo),115 (34),103, (45), 102 (16), 77 (34), 76 (12), 63 (12), 51 (24) and 50 (17). (E)-1,l-Dichloro-4-phenylbut-3-en-2-one7e-c (Found: C, 55.5; H, 3.9.C1,H,Cl,O requires C,55.84;H, 3.75); v,,,/cm-' 3060 and 3020(CSH) and 1680(C=O);6,6.0 (1 H, s, CHCl,), 7.2(1 H, d, J 16, CHSHCO), 7.8 (1 H, d, J 16, CHSHCO) and 7.4-7.6(5 H, my Ph); 6,69.6 (CHCl,), 117.4(CH=CHCO), 128.6, 128.8, 131.3 and 133.5 (C,H,), 147.7 (CHSHCO) and 185.4 (C=O); m/z 218 (M' + 4, 1), 216 (M+ + 2, 3), 214 (M++ 4),131 (loo), 103 (36), 77 (22) and 51 (12).1,1 -Dibromo-4-phenylbut-3-yn-2-one7f-a (Found: C, 39.6;H, 2.2.C,oH,Br,O requires C, 39.78;H, 2.00); v,,,/cm-' 21 80 (CS) and 1660 (GO); 6H5.9(1 H, s, CHBr,), 7.3-7.4(3 H, m, 2 x CH,,CH,) and 7.6 (2 H, d, J 8, CH,); 6c 42.3 (CHBr,), 83.0and 97.3(Ce), 118.7, 128.6, 131.6 and 133.4(C,H,) and 173.3(C=O); m/z 304 (M++ 4, l),302 (Mf + 2, l), 300 (M+,1) and 129 (100). 1 -Bromo-1 -chloro-4-phenylbut-3-yn-2-one7f-b (Found: C, 46.4; H, 2.5.C,oH,BrCIO requires C, 46.64; H, 2.35); v,,,/cm-' 2180 (Cg) and 1680 (C=O); 6,6.0 (1 H, s, CHBrCl) and 7.3-7.6(5 H, m, Ph); 6, 56.7(CHBrCl),83.1and 97.4(CS), 118.6, 128.6, 131.5 and 133.3 (C,H,) and 173.5 (c=O);m/z 260 (M' + 4, 1), 258 (M' + 2, 1), 256 (M+,l)and 129 (100). l,l-Dichloro-4-phenylbut-3-yn-2-one7f-c (Found: C, 56.1;H, 2.6.CloH,Cl,O requires C, 56.38;H, 2.84); v,,,/cm-' 2200 (Cg)and 1680 (C=O);6,6.0 (1 H,s, CHCl,) and 7.4-7.6 (5 H, m, Ph); 69.8(CHC12),83.0and 97.2(Cg), 118.0, 128.2, 131.3 and 133.0(C,H,) and173.0 (EO);m/z 130 (llx),129 (M' -CHCl,, loo), 101 (12), 87 (ll), 85 (40),83 (59, 77 (13), 76 (ll), 75 (32), 74 (35), 63 (14), 62 (18), 61 (13), 51 (19),50 (31), 49 (13), 48 (37), 47 (12) and 39 (10).Acknowledgements We thank Dr. P. Bernad (Servicio de Espectroscopia de Masas, Universidad de Oviedo) for spectroscopic mass determinations. References 1 Preliminary communication: J. Barluenga, L. Llavona, J. M. Concellon and M. Yus, J. Chem. Soc., Perkin Trans.1, 1990,417. 2 For example, see T. Sakai, E. Amano, K. Miyata, M. Utaka and A. Takeda, Bull. Chem. Soc. Jpn., 1987,60, 1945; T. Sakai, M. Ishikawa, E. Amano, M. Utaka and A. Takeda, Bull. Chem. Soc. Jpn., 1987,60, 2295. J. CHEM. SOC. PERKIN TRANS. I 1991 3 For recent reviews see R. Noyori and Y. Hayakawa, Org. React., 1983,29, 163; J. Mann, Tetrahedron, 1986,42,4611. 4 X. Lei, C. Doubleday and N. J. Turro, Tetrahedron Lett., 1986, 27, 467 1.5 J. Barluenga, J. Florez and M. Yus, Synthesis, 1983,647. 6 H. Greuter, P. Bissig, P. Martin, V. Flueck and L. Gsell, Pestic. Sci., 1980,11, 148 (Chem. Abstr., 1981,94,102874~). 7 N. De Kimpe, L. Moens, R. Verhe, L. De Buyck and N. Schamp, Tetrahedron Lett., 1982,23, 789. 8 For example, see T. Morimoto and M. Sekiya, Synthesis, 1981, 308; T. Morimoto and M. Sekiya, Chem. Pharm. Bull., 1982,30,3513; L. S. Liebeskind and S. L. Baysdon, Tetrahedron Lett., 1984,25, 1747. 9 P. Butinelli, M. A. Loreto, L. Pellacani and P. A. Tardella, J. Chem. Res. (S), 1985, 158. 10 A. F. Greene, J. P. Lansard, J. L. Luche and C. Petrier, J. Org. Chem., 1983,48,4763. 11 For example, see T. Hudlicky, B. C. Ranu, S. M. Naqvi and A.Srnak, J. Org. Chem., 1985,50, 123; G. H. Posner, J. P. Mallamo and A. Y. Black, Tetrahedron, 1981,37, 3921. 12 N. De Kimpe and R. Verhe, The Chemistry of a-Haloketones, a-Haloaldehydes and a-Haloimines, Wiley, Chichester, 1988. 13 For the preparation of cyclic a,a-dihalogeno ketones see, e.g., D. A. Bak and W. T. Brady, J. Org. Chem., 1979, 44, 107; A. E. Greene and J. P. Depres, J. Am. Chem. Soc., 1979, 101,4003; G. F. Hambly and T. H. Chan, Tetrahedron Lett., 1986,27,2563; W. T. Brady and R. M. Lloyd, J. Org. Chem., 1981, 46, 1322; A. Roeding and E. M. Ganns, Liebigs Ann. Chem., 1982, 406. For the preparation of unsaturated ,a-dihalogeno ketones see, e.g., H. Hamana and T. Sugasawa, Chem. Lett., 1985,575. 14 (a) From ketimines see, e.g., W.Coppens and N. Schamp, Bull. SOC. Chim. Belg., 1972,81, 643; N. Schamp, N. De Kimpe and W. Coppens, Tetrahedron, 1975,31, 2081. (b) From acetylenes see, eg., S. F. Reed, J. Org. Chem., 1965, 30, 2195. (c) From dichloroacetyl chloride see, e.g., B. Fohlisch and R. Flogaus, Synthesis, 1984, 734. (d) From diazo ketones see, e.g., C. Rappe and B. Albrecht, Actu Chem. Scand., 1966, 20, 253. (e) By cathodic reduction see, e.g., T. Shono, N. Kise, A. Yamazaki and H. Ohmizu, Tetrahedron Lett., 1982,23, 1609. 15 J. Villieras and M. Rambaud, C.R. Seances Acad. Sci. Paris, Ser. C, 1980,290,295. 16 For the preparation of a,a-dihalogeno ketones from a-halogeno ketones see, e.g., B. Modari and E. Khoshdel, J. Org. Chem., 1977, 42, 3527. 17 J. Barluenga, J. L. Fernandez-Simon, J. M. Concellon and M. Yus, J. Chem. SOC., Perkin Trans. 1, 1989,77, and references cited therein. 18 J. Barluenga, J. L. Fernandez-Simon, J. M. Concellon and M. Yus, J. Chem. Soc., Perkin Trans. 1, 1989, 691. 19 X. Creary, J. Org. Chem., 1987,52,5026. 20 Handbook of Chemistry and Physics, C.R.C. Press, Cleveland, 55th edn., 1974. 21 D. P. Wyman and P. R. Kaufman, J. Org. Chem., 1964,29, 1956. 22 J. Villieras, Bull. SOC.Chim. Fr., 1967, 1520. 23 J. Villieras, C. Bacquet and J. F. Normant, Bull. Soc. Chim. Fr., 1975, 1797. 24 C. Bacquet, J. Villieras and J. F. Normant, C.R. Seances Acad. Sci. Paris, Ser. C, 1974,278,929. Paper 0/03266B Received 20th July 1990 Accepted 13th September 1990