Conjugate Michael-additions with mixed diorganozincs

摘要

J. Chem. Soc. Perkin Trans. 1 1997 3117 Conjugate Michael-additions with mixed diorganozincs Philip Jones and Paul Knochel * Fachbereich Chemie der Philipps-Universitauml;t Marburg Hans-Meerwein-Straszlig;e 35032 Marburg Germany Mixed diorganozincs (RZnCH2SiMe3; R = alkyl aryl) undergo selective transfer of the R group in a 1,4-fashion to various Michael-acceptors. Diorganozincs are a useful class of organometallic intermediates. 1 They can be readily prepared via iodinendash;zinc exchange 2 or boronndash;zinc exchange 3 and tolerate the presence of numerous functional groups.1ndash;4 In the presence of transition metal catalysts they react with various electrophiles leading to polyfunctional products. Recently we have found that a polar cosolvent like N-methylpyrrolidinone (NMP) allows the 1,4- addition 5 to proceed in the absence of any copper or transition metal catalyst.Unfortunately only one organic group of the diorganozinc is transferred to an organic electrophile. However we could show that mixed diorganozincs bearing a trimethylsilylmethyl group (RZnCH2SiMe3 1) can be readily prepared and characterized spectroscopically.6 It was found that the CH2SiMe3 group plays the role of a non-transferable group which avoids the waste of an organic residue attached to zinc. This proves to be especially important for the performance of asymmetric additions to aldehydes.6 In preliminary experiments we have shown that the reagents 1 add to cyclohexenone.6 Herein we wish to report that mixed diorganozincs of type 1 react with a variety of Michael-acceptors leading to 1,4-adducts of type 3 in good yields (Scheme 1 and Table 1).Thus the reaction of 2-furyllithium with (trimethylsilylmethyl) zinc iodide in THF at 240 8C furnishes the mixed (trimethylsilylmethyl)(2-furyl)zinc which was allowed to react at 230 8C with hex-4-en-3-one 2a (ca. 0.7 equiv.) in the presence of trimethylsilyl bromide7 in NMP affording the Michaeladduct 3a as sole product in 95 yield (see entry 1 of Table 1). Secondary zinc reagents or functionalized dialkylzincs like (4- chlorobutyl)(trimethylsilylmethyl)zinc can also be used with equal efficiency (see entries 2 and 3 of Table 1). In this case the mixed zinc reagent is best prepared by adding commercially available Me3SiCH2Li to 4-chlorobutylzinc iodide obtained by the direct insertion of zinc dust into 4-chloroiodobutane 1 in THF. The mixed reaction conditions involved in these Michaeladditions allow the use of reactive vinyl methyl ketone 2b which adds various aryl and alkyl zinc reagents in 74ndash;92 yield (entries 4ndash;6).Whereas the addition of organocuprates to unsaturated aldehydes often requires the use of highly polar cosolvents like HMPA,8 the addition of the mixed zinc reagent to unsaturated aldehydes like 2-methylbut-2-enal 2c (entries 7ndash;8) or the reactive b-unsubstituted aldehyde 2-butylacryl- Scheme 1 Reagents and conditions i Me3SiBr (2 equiv.) THF NMP 230 8C 12 h X O X O i + 1 2 3 FG-R X = Alkyl H OR FG R ZnCH2SiMe3 FG R = Alkyl Aryl aldehyde (2d; entries 9ndash;10) occurs smoothly providing the functionalized aldehydes 2gndash;j in 51ndash;91 yield. No 1,2-addition products are observed (see Experimental section). Also the conjugated addition to acrylic esters like butyl acrylate produces the expected Michael-adducts 3kndash;l under similar reaction conditions (230 8C 3 h) in 76ndash;86 yield (entries 11 and 12).The addition to acrylonitrile 2f affords the conjugated addition product 3m in which the trimethylsilyl group has been incorporated in the position a to the cyano group (3m 54; entry 13). Finally addition to nitroolefins like 1-nitrobutene 2g leads to nitroalkanes such as 3n and 3o in 64ndash;76 yield (entries 14 and 15). In no case was transfer of the trimethylsilylmethyl group observed. In summary we have shown that the mixed zinc reagents 1 undergo a conjugate addition to various Michael-acceptors. Extension of these reactions using other chiral non-transferable groups is underway. Experimental Standard procedure preparation of ethyl 6-(formyl)decanoate 3j 1,2-Dibromoethane (0.2 cm3) was added dropwise to a stirred mixture of zinc dust (1.57 g 24 mmol) in THF (6 cm3) at room temperature under argon whilst heating with a heat gun to boil the solvent gently.Upon complete addition the mixture was cooled to room temperature and then trimethylsilyl chloride (0.2 cm3) was added dropwise over 5 min again with gentle heating of the solvent. After complete addition the mixture was stirred at room temperature for a further 5 min. Ethyl 4- iodobutanoate (1.45 g 6 mmol) was added dropwise over 5 min and then the reaction was heated at 50 8C for 3 h and the zinc insertion reaction monitored by GC analysis. When the reaction was complete the reaction mixture was cooled to room temperature and the excess zinc dust allowed to settle for 15 min.The pale grey solution was transferred to a flame dried flask and cooled to 240 8C. A solution of trimethylsilylmethyllithium (6 mmol) in pentane (1.0 mol dm23 6.0 cm3) was added dropwise over 3 min to the zinc iodide solution and then stirred at 240 8C for one hour. NMP (1 cm3) trimethylsilyl bromide (1.0 cm3 8 mmol) and then 2-butylacrylaldehyde 2d (0.53 cm3 4 mmol) were added to this reaction mixture at 260 8C. The reaction was warmed to 230 8C and stirred at this temperature for 3 h. The reaction was poured into saturated aqueous ammonium chloride (50 cm3) and worked up as usual. The residue was further purified by column chromatography on silica using 15 diethyl etherndash;light petroleum as eluent to give the aldehyde 3j (0.65 g 71) as a colourless oil.Acknowledgements The authors wish to thank the DFG (SFB 260 and Leibniz program) for generous financial support and the Royal Society for an award (to P. J.) under the European Science Exchange Programme. 3118 J. Chem. Soc. Perkin Trans. 1 1997 Table 1 Michael-additions of the mixed diorganozincs 1 in THFndash;NMP mixtures Entry Michael-acceptor a RZnCH2SiMe3 Product 3 Yield () b 1 2a 2-Furyl O O Me Et 3a 95 2 2a c-Hexyl 3b O Me Et c-Hex 87 3 2a Cl(CH2)4 O Me Et Cl(CH2)4 3c 71 4 2b 2-Furyl O O Me 3d 92 5 2b EtO2C(CH2)3 EtO2C(CH2)5COMe 3e 81 6 2b Cl(CH2)4 Cl(CH2)5COMe 3f 74 7 2c c-Hexyl c-Hex CHO Me Me 3g 91 8 2c EtO2C(CH2)3 EtO2C(CH2)3 CHO Me Me 3h 51 9 2d c-Hexyl c-Hex Bu CHO 3i 68 10 2d EtO2C(CH2)3 3j Bu EtO2C(CH2)4 CHO 71 11 2e EtO2C(CH2)3 EtO2C(CH2)5CO2Bu 3k 86 12 2e Cl(CH2)4 Cl(CH2)6CO2Bu 3l 76 13 2f c-Hexyl c-Hex CN SiMe3 3m 54 14 2g c-Hexyl c-Hex NO2 Et 3n 76 15 2g 2-Furyl O NO2 Et 3o 64 a 2a Hex-4-en-3-one; 2b methyl vinyl ketone; 2c 2-methylbut-2-enal; 2d 2-butylacrylaldehyde; 2e butyl acrylate; 2f acrylonitrile; 2g 1-nitrobutene.b Isolated yields of analytically pure products. References 1 P. Knochel and R. D. Singer Chem. Rev. 1993 93 2117. 2 M. J. Rozema S. AchyuthaRao and P. Knochel J. Org. Chem. 1992 57 1956. 3 F. Langer L. Schwink A. Devasagayaraj and P.-Y. Chavant J. Org. Chem. 1996 61 8229. 4 P. Knochel Synlett 1995 393. 5 C. K. Reddy A. Devasagayaraj and P. Knochel Tetrahedron Lett. 1996 37 4495. 6 S. Berger F. Langer C. Lutz P. Knochel T. A. Mobley and C. K. Reddy Angew. Chem. Int. Ed. Engl. 1997 36 1496. 7 (a) M.Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1988 44 2055; (b) M. Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1989 45 535; (c) M. Bergdahl M. Nilsson and T. Olsson J. Organomet. Chem. 1990 391 C19. 8 (a) Y. Horiguchi S. Matsuzawa E. Nakamura and I. Kuwajima Tetrahedron Lett. 1986 27 4025; (b) E. Nakamura S. Matsuzawa Y. Horiguchi and I. Kuwajima Tetrahedron Lett. 1986 27 4029. Paper 7/06637F Received 8th September 1997 Accepted 12th September 1997 J. Chem. Soc. Perkin Trans. 1 1997 3117 Conjugate Michael-additions with mixed diorganozincs Philip Jones and Paul Knochel * Fachbereich Chemie der Philipps-Universitauml;t Marburg Hans-Meerwein-Straszlig;e 35032 Marburg Germany Mixed diorganozincs (RZnCH2SiMe3; R = alkyl aryl) undergo selective transfer of the R group in a 1,4-fashion to various Michael-acceptors.Diorganozincs are a useful class of organometallic intermediates. 1 They can be readily prepared via iodinendash;zinc exchange 2 or boronndash;zinc exchange 3 and tolerate the presence of numerous functional groups.1ndash;4 In the presence of transition metal catalysts they react with various electrophiles leading to polyfunctional products. Recently we have found that a polar cosolvent like N-methylpyrrolidinone (NMP) allows the 1,4- addition 5 to proceed in the absence of any copper or transition metal catalyst. Unfortunately only one organic group of the diorganozinc is transferred to an organic electrophile. However we could show that mixed diorganozincs bearing a trimethylsilylmethyl group (RZnCH2SiMe3 1) can be readily prepared and characterized spectroscopically.6 It was found that the CH2SiMe3 group plays the role of a non-transferable group which avoids the waste of an organic residue attached to zinc.This proves to be especially important for the performance of asymmetric additions to aldehydes.6 In preliminary experiments we have shown that the reagents 1 add to cyclohexenone.6 Herein we wish to report that mixed diorganozincs of type 1 react with a variety of Michael-acceptors leading to 1,4-adducts of type 3 in good yields (Scheme 1 and Table 1). Thus the reaction of 2-furyllithium with (trimethylsilylmethyl) zinc iodide in THF at 240 8C furnishes the mixed (trimethylsilylmethyl)(2-furyl)zinc which was allowed to react at 230 8C with hex-4-en-3-one 2a (ca. 0.7 equiv.) in the presence of trimethylsilyl bromide7 in NMP affording the Michaeladduct 3a as sole product in 95 yield (see entry 1 of Table 1).Secondary zinc reagents or functionalized dialkylzincs like (4- chlorobutyl)(trimethylsilylmethyl)zinc can also be used with equal efficiency (see entries 2 and 3 of Table 1). In this case the mixed zinc reagent is best prepared by adding commercially available Me3SiCH2Li to 4-chlorobutylzinc iodide obtained by the direct insertion of zinc dust into 4-chloroiodobutane 1 in THF. The mixed reaction conditions involved in these Michaeladditions allow the use of reactive vinyl methyl ketone 2b which adds various aryl and alkyl zinc reagents in 74ndash;92 yield (entries 4ndash;6). Whereas the addition of organocuprates to unsaturated aldehydes often requires the use of highly polar cosolvents like HMPA,8 the addition of the mixed zinc reagent to unsaturated aldehydes like 2-methylbut-2-enal 2c (entries 7ndash;8) or the reactive b-unsubstituted aldehyde 2-butylacryl- Scheme 1 Reagents and conditions i Me3SiBr (2 equiv.) THF NMP 230 8C 12 h X O X O i + 1 2 3 FG-R X = Alkyl H OR FG R ZnCH2SiMe3 FG R = Alkyl Aryl aldehyde (2d; entries 9ndash;10) occurs smoothly providing the functionalized aldehydes 2gndash;j in 51ndash;91 yield.No 1,2-addition products are observed (see Experimental section). Also the conjugated addition to acrylic esters like butyl acrylate produces the expected Michael-adducts 3kndash;l under similar reaction conditions (230 8C 3 h) in 76ndash;86 yield (entries 11 and 12). The addition to acrylonitrile 2f affords the conjugated addition product 3m in which the trimethylsilyl group has been incorporated in the position a to the cyano group (3m 54; entry 13).Finally addition to nitroolefins like 1-nitrobutene 2g leads to nitroalkanes such as 3n and 3o in 64ndash;76 yield (entries 14 and 15). In no case was transfer of the trimethylsilylmethyl group observed. In summary we have shown that the mixed zinc reagents 1 undergo a conjugate addition to various Michael-acceptors. Extension of these reactions using other chiral non-transferable groups is underway. Experimental Standard procedure preparation of ethyl 6-(formyl)decanoate 3j 1,2-Dibromoethane (0.2 cm3) was added dropwise to a stirred mixture of zinc dust (1.57 g 24 mmol) in THF (6 cm3) at room temperature under argon whilst heating with a heat gun to boil the solvent gently. Upon complete addition the mixture was cooled to room temperature and then trimethylsilyl chloride (0.2 cm3) was added dropwise over 5 min again with gentle heating of the solvent.After complete addition the mixture was stirred at room temperature for a further 5 min. Ethyl 4- iodobutanoate (1.45 g 6 mmol) was added dropwise over 5 min and then the reaction was heated at 50 8C for 3 h and the zinc insertion reaction monitored by GC analysis. When the reaction was complete the reaction mixture was cooled to room temperature and the excess zinc dust allowed to settle for 15 min. The pale grey solution was transferred to a flame dried flask and cooled to 240 8C. A solution of trimethylsilylmethyllithium (6 mmol) in pentane (1.0 mol dm23 6.0 cm3) was added dropwise over 3 min to the zinc iodide solution and then stirred at 240 8C for one hour.NMP (1 cm3) trimethylsilyl bromide (1.0 cm3 8 mmol) and then 2-butylacrylaldehyde 2d (0.53 cm3 4 mmol) were added to this reaction mixture at 260 8C. The reaction was warmed to 230 8C and stirred at this temperature for 3 h. The reaction was poured into saturated aqueous ammonium chloride (50 cm3) and worked up as usual. The residue was further purified by column chromatography on silica using 15 diethyl etherndash;light petroleum as eluent to give the aldehyde 3j (0.65 g 71) as a colourless oil. Acknowledgements The authors wish to thank the DFG (SFB 260 and Leibniz program) for generous financial support and the Royal Society for an award (to P. J.) under the European Science Exchange Programme. 3118 J. Chem. Soc. Perkin Trans. 1 1997 Table 1 Michael-additions of the mixed diorganozincs 1 in THFndash;NMP mixtures Entry Michael-acceptor a RZnCH2SiMe3 Product 3 Yield () b 1 2a 2-Furyl O O Me Et 3a 95 2 2a c-Hexyl 3b O Me Et c-Hex 87 3 2a Cl(CH2)4 O Me Et Cl(CH2)4 3c 71 4 2b 2-Furyl O O Me 3d 92 5 2b EtO2C(CH2)3 EtO2C(CH2)5COMe 3e 81 6 2b Cl(CH2)4 Cl(CH2)5COMe 3f 74 7 2c c-Hexyl c-Hex CHO Me Me 3g 91 8 2c EtO2C(CH2)3 EtO2C(CH2)3 CHO Me Me 3h 51 9 2d c-Hexyl c-Hex Bu CHO 3i 68 10 2d EtO2C(CH2)3 3j Bu EtO2C(CH2)4 CHO 71 11 2e EtO2C(CH2)3 EtO2C(CH2)5CO2Bu 3k 86 12 2e Cl(CH2)4 Cl(CH2)6CO2Bu 3l 76 13 2f c-Hexyl c-Hex CN SiMe3 3m 54 14 2g c-Hexyl c-Hex NO2 Et 3n 76 15 2g 2-Furyl O NO2 Et 3o 64 a 2a Hex-4-en-3-one; 2b methyl vinyl ketone; 2c 2-methylbut-2-enal; 2d 2-butylacrylaldehyde; 2e butyl acrylate; 2f acrylonitrile; 2g 1-nitrobutene.b Isolated yields of analytically pure products.References 1 P. Knochel and R. D. Singer Chem. Rev. 1993 93 2117. 2 M. J. Rozema S. AchyuthaRao and P. Knochel J. Org. Chem. 1992 57 1956. 3 F. Langer L. Schwink A. Devasagayaraj and P.-Y. Chavant J. Org. Chem. 1996 61 8229. 4 P. Knochel Synlett 1995 393. 5 C. K. Reddy A. Devasagayaraj and P. Knochel Tetrahedron Lett. 1996 37 4495. 6 S. Berger F. Langer C. Lutz P. Knochel T. A. Mobley and C. K. Reddy Angew. Chem. Int. Ed. Engl. 1997 36 1496. 7 (a) M. Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1988 44 2055; (b) M. Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1989 45 535; (c) M. Bergdahl M. Nilsson and T. Olsson J. Organomet. Chem. 1990 391 C19. 8 (a) Y. Horiguchi S. Matsuzawa E. Nakamura and I. Kuwajima Tetrahedron Lett.1986 27 4025; (b) E. Nakamura S. Matsuzawa Y. Horiguchi and I. Kuwajima Tetrahedron Lett. 1986 27 4029. Paper 7/06637F Received 8th September 1997 Accepted 12th September 1997 J. Chem. Soc. Perkin Trans. 1 1997 3117 Conjugate Michael-additions with mixed diorganozincs Philip Jones and Paul Knochel * Fachbereich Chemie der Philipps-Universitauml;t Marburg Hans-Meerwein-Straszlig;e 35032 Marburg Germany Mixed diorganozincs (RZnCH2SiMe3; R = alkyl aryl) undergo selective transfer of the R group in a 1,4-fashion to various Michael-acceptors. Diorganozincs are a useful class of organometallic intermediates. 1 They can be readily prepared via iodinendash;zinc exchange 2 or boronndash;zinc exchange 3 and tolerate the presence of numerous functional groups.1ndash;4 In the presence of transition metal catalysts they react with various electrophiles leading to polyfunctional products.Recently we have found that a polar cosolvent like N-methylpyrrolidinone (NMP) allows the 1,4- addition 5 to proceed in the absence of any copper or transition metal catalyst. Unfortunately only one organic group of the diorganozinc is transferred to an organic electrophile. However we could show that mixed diorganozincs bearing a trimethylsilylmethyl group (RZnCH2SiMe3 1) can be readily prepared and characterized spectroscopically.6 It was found that the CH2SiMe3 group plays the role of a non-transferable group which avoids the waste of an organic residue attached to zinc. This proves to be especially important for the performance of asymmetric additions to aldehydes.6 In preliminary experiments we have shown that the reagents 1 add to cyclohexenone.6 Herein we wish to report that mixed diorganozincs of type 1 react with a variety of Michael-acceptors leading to 1,4-adducts of type 3 in good yields (Scheme 1 and Table 1).Thus the reaction of 2-furyllithium with (trimethylsilylmethyl) zinc iodide in THF at 240 8C furnishes the mixed (trimethylsilylmethyl)(2-furyl)zinc which was allowed to react at 230 8C with hex-4-en-3-one 2a (ca. 0.7 equiv.) in the presence of trimethylsilyl bromide7 in NMP affording the Michaeladduct 3a as sole product in 95 yield (see entry 1 of Table 1). Secondary zinc reagents or functionalized dialkylzincs like (4- chlorobutyl)(trimethylsilylmethyl)zinc can also be used with equal efficiency (see entries 2 and 3 of Table 1). In this case the mixed zinc reagent is best prepared by adding commercially available Me3SiCH2Li to 4-chlorobutylzinc iodide obtained by the direct insertion of zinc dust into 4-chloroiodobutane 1 in THF.The mixed reaction conditions involved in these Michaeladditions allow the use of reactive vinyl methyl ketone 2b which adds various aryl and alkyl zinc reagents in 74ndash;92 yield (entries 4ndash;6). Whereas the addition of organocuprates to unsaturated aldehydes often requires the use of highly polar cosolvents like HMPA,8 the addition of the mixed zinc reagent to unsaturated aldehydes like 2-methylbut-2-enal 2c (entries 7ndash;8) or the reactive b-unsubstituted aldehyde 2-butylacryl- Scheme 1 Reagents and conditions i Me3SiBr (2 equiv.) THF NMP 230 8C 12 h X O X O i + 1 2 3 FG-R X = Alkyl H OR FG R ZnCH2SiMe3 FG R = Alkyl Aryl aldehyde (2d; entries 9ndash;10) occurs smoothly providing the functionalized aldehydes 2gndash;j in 51ndash;91 yield.No 1,2-addition products are observed (see Experimental section). Also the conjugated addition to acrylic esters like butyl acrylate produces the expected Michael-adducts 3kndash;l under similar reaction conditions (230 8C 3 h) in 76ndash;86 yield (entries 11 and 12). The addition to acrylonitrile 2f affords the conjugated addition product 3m in which the trimethylsilyl group has been incorporated in the position a to the cyano group (3m 54; entry 13). Finally addition to nitroolefins like 1-nitrobutene 2g leads to nitroalkanes such as 3n and 3o in 64ndash;76 yield (entries 14 and 15). In no case was transfer of the trimethylsilylmethyl group observed. In summary we have shown that the mixed zinc reagents 1 undergo a conjugate addition to various Michael-acceptors.Extension of these reactions using other chiral non-transferable groups is underway. Experimental Standard procedure preparation of ethyl 6-(formyl)decanoate 3j 1,2-Dibromoethane (0.2 cm3) was added dropwise to a stirred mixture of zinc dust (1.57 g 24 mmol) in THF (6 cm3) at room temperature under argon whilst heating with a heat gun to boil the solvent gently. Upon complete addition the mixture was cooled to room temperature and then trimethylsilyl chloride (0.2 cm3) was added dropwise over 5 min again with gentle heating of the solvent. After complete addition the mixture was stirred at room temperature for a further 5 min. Ethyl 4- iodobutanoate (1.45 g 6 mmol) was added dropwise over 5 min and then the reaction was heated at 50 8C for 3 h and the zinc insertion reaction monitored by GC analysis.When the reaction was complete the reaction mixture was cooled to room temperature and the excess zinc dust allowed to settle for 15 min. The pale grey solution was transferred to a flame dried flask and cooled to 240 8C. A solution of trimethylsilylmethyllithium (6 mmol) in pentane (1.0 mol dm23 6.0 cm3) was added dropwise over 3 min to the zinc iodide solution and then stirred at 240 8C for one hour. NMP (1 cm3) trimethylsilyl bromide (1.0 cm3 8 mmol) and then 2-butylacrylaldehyde 2d (0.53 cm3 4 mmol) were added to this reaction mixture at 260 8C. The reaction was warmed to 230 8C and stirred at this temperature for 3 h. The reaction was poured into saturated aqueous ammonium chloride (50 cm3) and worked up as usual.The residue was further purified by column chromatography on silica using 15 diethyl etherndash;light petroleum as eluent to give the aldehyde 3j (0.65 g 71) as a colourless oil. Acknowledgements The authors wish to thank the DFG (SFB 260 and Leibniz program) for generous financial support and the Royal Society for an award (to P. J.) under the European Science Exchange Programme. 3118 J. Chem. Soc. Perkin Trans. 1 1997 Table 1 Michael-additions of the mixed diorganozincs 1 in THFndash;NMP mixtures Entry Michael-acceptor a RZnCH2SiMe3 Product 3 Yield () b 1 2a 2-Furyl O O Me Et 3a 95 2 2a c-Hexyl 3b O Me Et c-Hex 87 3 2a Cl(CH2)4 O Me Et Cl(CH2)4 3c 71 4 2b 2-Furyl O O Me 3d 92 5 2b EtO2C(CH2)3 EtO2C(CH2)5COMe 3e 81 6 2b Cl(CH2)4 Cl(CH2)5COMe 3f 74 7 2c c-Hexyl c-Hex CHO Me Me 3g 91 8 2c EtO2C(CH2)3 EtO2C(CH2)3 CHO Me Me 3h 51 9 2d c-Hexyl c-Hex Bu CHO 3i 68 10 2d EtO2C(CH2)3 3j Bu EtO2C(CH2)4 CHO 71 11 2e EtO2C(CH2)3 EtO2C(CH2)5CO2Bu 3k 86 12 2e Cl(CH2)4 Cl(CH2)6CO2Bu 3l 76 13 2f c-Hexyl c-Hex CN SiMe3 3m 54 14 2g c-Hexyl c-Hex NO2 Et 3n 76 15 2g 2-Furyl O NO2 Et 3o 64 a 2a Hex-4-en-3-one; 2b methyl vinyl ketone; 2c 2-methylbut-2-enal; 2d 2-butylacrylaldehyde; 2e butyl acrylate; 2f acrylonitrile; 2g 1-nitrobutene.b Isolated yields of analytically pure products. References 1 P. Knochel and R. D. Singer Chem. Rev. 1993 93 2117. 2 M. J. Rozema S. AchyuthaRao and P. Knochel J. Org. Chem. 1992 57 1956. 3 F. Langer L. Schwink A. Devasagayaraj and P.-Y. Chavant J. Org. Chem. 1996 61 8229. 4 P. Knochel Synlett 1995 393.5 C. K. Reddy A. Devasagayaraj and P. Knochel Tetrahedron Lett. 1996 37 4495. 6 S. Berger F. Langer C. Lutz P. Knochel T. A. Mobley and C. K. Reddy Angew. Chem. Int. Ed. Engl. 1997 36 1496. 7 (a) M. Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1988 44 2055; (b) M. Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1989 45 535; (c) M. Bergdahl M. Nilsson and T. Olsson J. Organomet. Chem. 1990 391 C19. 8 (a) Y. Horiguchi S. Matsuzawa E. Nakamura and I. Kuwajima Tetrahedron Lett. 1986 27 4025; (b) E. Nakamura S. Matsuzawa Y. Horiguchi and I. Kuwajima Tetrahedron Lett. 1986 27 4029. Paper 7/06637F Received 8th September 1997 Accepted 12th September 1997 J. Chem. Soc. Perkin Trans. 1 1997 3117 Conjugate Michael-additions with mixed diorganozincs Philip Jones and Paul Knochel * Fachbereich Chemie der Philipps-Universitauml;t Marburg Hans-Meerwein-Straszlig;e 35032 Marburg Germany Mixed diorganozincs (RZnCH2SiMe3; R = alkyl aryl) undergo selective transfer of the R group in a 1,4-fashion to various Michael-acceptors.Diorganozincs are a useful class of organometallic intermediates. 1 They can be readily prepared via iodinendash;zinc exchange 2 or boronndash;zinc exchange 3 and tolerate the presence of numerous functional groups.1ndash;4 In the presence of transition metal catalysts they react with various electrophiles leading to polyfunctional products. Recently we have found that a polar cosolvent like N-methylpyrrolidinone (NMP) allows the 1,4- addition 5 to proceed in the absence of any copper or transition metal catalyst. Unfortunately only one organic group of the diorganozinc is transferred to an organic electrophile.However we could show that mixed diorganozincs bearing a trimethylsilylmethyl group (RZnCH2SiMe3 1) can be readily prepared and characterized spectroscopically.6 It was found that the CH2SiMe3 group plays the role of a non-transferable group which avoids the waste of an organic residue attached to zinc. This proves to be especially important for the performance of asymmetric additions to aldehydes.6 In preliminary experiments we have shown that the reagents 1 add to cyclohexenone.6 Herein we wish to report that mixed diorganozincs of type 1 react with a variety of Michael-acceptors leading to 1,4-adducts of type 3 in good yields (Scheme 1 and Table 1). Thus the reaction of 2-furyllithium with (trimethylsilylmethyl) zinc iodide in THF at 240 8C furnishes the mixed (trimethylsilylmethyl)(2-furyl)zinc which was allowed to react at 230 8C with hex-4-en-3-one 2a (ca.0.7 equiv.) in the presence of trimethylsilyl bromide7 in NMP affording the Michaeladduct 3a as sole product in 95 yield (see entry 1 of Table 1). Secondary zinc reagents or functionalized dialkylzincs like (4- chlorobutyl)(trimethylsilylmethyl)zinc can also be used with equal efficiency (see entries 2 and 3 of Table 1). In this case the mixed zinc reagent is best prepared by adding commercially available Me3SiCH2Li to 4-chlorobutylzinc iodide obtained by the direct insertion of zinc dust into 4-chloroiodobutane 1 in THF. The mixed reaction conditions involved in these Michaeladditions allow the use of reactive vinyl methyl ketone 2b which adds various aryl and alkyl zinc reagents in 74ndash;92 yield (entries 4ndash;6).Whereas the addition of organocuprates to unsaturated aldehydes often requires the use of highly polar cosolvents like HMPA,8 the addition of the mixed zinc reagent to unsaturated aldehydes like 2-methylbut-2-enal 2c (entries 7ndash;8) or the reactive b-unsubstituted aldehyde 2-butylacryl- Scheme 1 Reagents and conditions i Me3SiBr (2 equiv.) THF NMP 230 8C 12 h X O X O i + 1 2 3 FG-R X = Alkyl H OR FG R ZnCH2SiMe3 FG R = Alkyl Aryl aldehyde (2d; entries 9ndash;10) occurs smoothly providing the functionalized aldehydes 2gndash;j in 51ndash;91 yield. No 1,2-addition products are observed (see Experimental section). Also the conjugated addition to acrylic esters like butyl acrylate produces the expected Michael-adducts 3kndash;l under similar reaction conditions (230 8C 3 h) in 76ndash;86 yield (entries 11 and 12).The addition to acrylonitrile 2f affords the conjugated addition product 3m in which the trimethylsilyl group has been incorporated in the position a to the cyano group (3m 54; entry 13). Finally addition to nitroolefins like 1-nitrobutene 2g leads to nitroalkanes such as 3n and 3o in 64ndash;76 yield (entries 14 and 15). In no case was transfer of the trimethylsilylmethyl group observed. In summary we have shown that the mixed zinc reagents 1 undergo a conjugate addition to various Michael-acceptors. Extension of these reactions using other chiral non-transferable groups is underway. Experimental Standard procedure preparation of ethyl 6-(formyl)decanoate 3j 1,2-Dibromoethane (0.2 cm3) was added dropwise to a stirred mixture of zinc dust (1.57 g 24 mmol) in THF (6 cm3) at room temperature under argon whilst heating with a heat gun to boil the solvent gently.Upon complete addition the mixture was cooled to room temperature and then trimethylsilyl chloride (0.2 cm3) was added dropwise over 5 min again with gentle heating of the solvent. After complete addition the mixture was stirred at room temperature for a further 5 min. Ethyl 4- iodobutanoate (1.45 g 6 mmol) was added dropwise over 5 min and then the reaction was heated at 50 8C for 3 h and the zinc insertion reaction monitored by GC analysis. When the reaction was complete the reaction mixture was cooled to room temperature and the excess zinc dust allowed to settle for 15 min. The pale grey solution was transferred to a flame dried flask and cooled to 240 8C.A solution of trimethylsilylmethyllithium (6 mmol) in pentane (1.0 mol dm23 6.0 cm3) was added dropwise over 3 min to the zinc iodide solution and then stirred at 240 8C for one hour. NMP (1 cm3) trimethylsilyl bromide (1.0 cm3 8 mmol) and then 2-butylacrylaldehyde 2d (0.53 cm3 4 mmol) were added to this reaction mixture at 260 8C. The reaction was warmed to 230 8C and stirred at this temperature for 3 h. The reaction was poured into saturated aqueous ammonium chloride (50 cm3) and worked up as usual. The residue was further purified by column chromatography on silica using 15 diethyl etherndash;light petroleum as eluent to give the aldehyde 3j (0.65 g 71) as a colourless oil. Acknowledgements The authors wish to thank the DFG (SFB 260 and Leibniz program) for generous financial support and the Royal Society for an award (to P.J.) under the European Science Exchange Programme. 3118 J. Chem. Soc. Perkin Trans. 1 1997 Table 1 Michael-additions of the mixed diorganozincs 1 in THFndash;NMP mixtures Entry Michael-acceptor a RZnCH2SiMe3 Product 3 Yield () b 1 2a 2-Furyl O O Me Et 3a 95 2 2a c-Hexyl 3b O Me Et c-Hex 87 3 2a Cl(CH2)4 O Me Et Cl(CH2)4 3c 71 4 2b 2-Furyl O O Me 3d 92 5 2b EtO2C(CH2)3 EtO2C(CH2)5COMe 3e 81 6 2b Cl(CH2)4 Cl(CH2)5COMe 3f 74 7 2c c-Hexyl c-Hex CHO Me Me 3g 91 8 2c EtO2C(CH2)3 EtO2C(CH2)3 CHO Me Me 3h 51 9 2d c-Hexyl c-Hex Bu CHO 3i 68 10 2d EtO2C(CH2)3 3j Bu EtO2C(CH2)4 CHO 71 11 2e EtO2C(CH2)3 EtO2C(CH2)5CO2Bu 3k 86 12 2e Cl(CH2)4 Cl(CH2)6CO2Bu 3l 76 13 2f c-Hexyl c-Hex CN SiMe3 3m 54 14 2g c-Hexyl c-Hex NO2 Et 3n 76 15 2g 2-Furyl O NO2 Et 3o 64 a 2a Hex-4-en-3-one; 2b methyl vinyl ketone; 2c 2-methylbut-2-enal; 2d 2-butylacrylaldehyde; 2e butyl acrylate; 2f acrylonitrile; 2g 1-nitrobutene.b Isolated yields of analytically pure products. References 1 P. Knochel and R. D. Singer Chem. Rev. 1993 93 2117. 2 M. J. Rozema S. AchyuthaRao and P. Knochel J. Org. Chem. 1992 57 1956. 3 F. Langer L. Schwink A. Devasagayaraj and P.-Y. Chavant J. Org. Chem. 1996 61 8229. 4 P. Knochel Synlett 1995 393. 5 C. K. Reddy A. Devasagayaraj and P. Knochel Tetrahedron Lett. 1996 37 4495. 6 S. Berger F. Langer C. Lutz P. Knochel T. A. Mobley and C. K. Reddy Angew. Chem. Int. Ed. Engl. 1997 36 1496. 7 (a) M. Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1988 44 2055; (b) M. Bergdahl E.-L. Lindstedt M. Nilsson and T. Olsson Tetrahedron 1989 45 535; (c) M. Bergdahl M. Nilsson and T. Olsson J. Organomet. Chem. 1990 391 C19. 8 (a) Y. Horiguchi S. Matsuzawa E. Nakamura and I. Kuwajima Tetrahedron Lett. 1986 27 4025; (b) E. Nakamura S. Matsuzawa Y. Horiguchi and I. Kuwajima Tetrahedron Lett. 1986 27 4029. Paper 7/06637F Received 8th September 1997 Accepted 12th September 1997