WO2006056166A2 - Procede d'addition d'amides, de carbamides, de lactames et de carbamates a des alcynes - Google Patents

Procede d'addition d'amides, de carbamides, de lactames et de carbamates a des alcynes Download PDF

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WO2006056166A2
WO2006056166A2 PCT/DE2005/002048 DE2005002048W WO2006056166A2 WO 2006056166 A2 WO2006056166 A2 WO 2006056166A2 DE 2005002048 W DE2005002048 W DE 2005002048W WO 2006056166 A2 WO2006056166 A2 WO 2006056166A2
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branched
linear
alkyl
heteroaryl
aryl
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WO2006056166A3 (fr
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Lukas Goossen
Jan E. Rauhaus
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Studiengesellschaft Kohle Mbh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/03—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C07D211/76—Oxygen atoms attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D223/08—Oxygen atoms
    • C07D223/10—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
    • C07D225/02—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/70—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms

Definitions

  • the invention relates to a process for the preparation of enamides, N-alkenylureas, N-alkenyllactams and N-alkenylcarbamates by reacting amides, ureas, lactams and carbamates with terminal alkynes in the presence of a transition metal catalyst.
  • enamides serve as versatile synthetic building blocks, for example, as a source of enantiomerically pure amides, amines, and amino acids as well as for the preparation of heterocycles (Scheme 1). Easy access to this class of compounds is therefore of great interest.
  • a BASF patent describes a process for preparing N-vinyl compounds by addition of nitrogen nucleophiles to acetylene, in which ruthenium (III) and osmium (III) salts are used as catalysts.
  • this process is strictly limited to the known highly reactive acetylene with respect to the alkyne component, unsuitable for other alkynes, and requires high temperatures and pressures.
  • the object of the present invention was to develop a generally applicable, mild process for the preparation of enamides, N-alkenylureas, N-alkenyllactams and N-alkenylcarbamates.
  • the particular difficulty was that the known catalysts for the addition of nucleophiles to alkynes such.
  • ruthenium (III) halides, Ru 3 CO 12 or ruthenium (II) arene compounds showed no activity for the desired reaction. Therefore, the catalysts had to be redeveloped, a systematic optimization of an existing catalyst system was not possible.
  • This method differs from the method of Watanabe et al. in particular by the catalyst used which is not prepared from Ru 3 CO 12 but from ruthenium compounds with carbon-containing ligands selected from the group alkyl, aryl, vinyl, benzyl, allyl, dienyl, olefin, diene, arene.
  • the substituents R 2 and R 3 are independently selectable from the series heteroatoms from the series H, S, Si, N, O, Cl, Br, I, B, linear and branched C 1 - C 10 alkyl or C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 - vinyl or heteroaryl selected from pyridine, pyrimidin, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole, thiophene, furan , linear and branched C 1 -C 10 -alkyloxy or C 1 -C 10 -aryloxy, halogenated linear and branched C 1 - C 10 alkyl or halogenated C 1 - C 10 aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1 - C 10
  • the fragment X is an atom from the series C, S, P and can itself further substituents from the series linear and branched C 1 - Qo-alkyl or C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 - alkyloxy or C 1 - C 10 aryloxy, halogenated linear and branched C 1 - Qo alkyl, or halogenated C 1 - C 10 aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1 - C 10 - arylaminocarbonyl , linear and branched C 1 - C 10 acyl, linear and branched C 1 - C 1 acyl, linear and branched C 1 - C 1
  • the substituent R 1 of the terminal alkyne is selectable from the series consisting of heteroatoms from the series S, Si, N, O, Cl, Br, I, B, linear and branched C 1 -C 10 -alkyl or C 1 -C 10 -aryl, vinyl or heteroaryl from the series pyridine, pyrimidine, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole, thiophene, furan, linear and branched C 1 - alkyloxy or C 1 - Qo-aryloxy, halogenated linear and branched C 1 - C 10 - alkyl, or halogenated C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1
  • the catalysts used are ruthenium organyl complexes, preferably ruthenium (II) organyl complexes, particularly preferably bis (organyl) ruthenium (II) complexes, and very particularly preferably bis (2-methylallyl) ruthenium (II) complexes.
  • the ruthenium is optionally stabilized by further ligands from the series amines, phosphines, N-heterocyclic carbenes, nitriles, olefins.
  • Phosphines are preferably used as ligands, particularly preferably phosphines are used in combination with amines, very particularly preferably a combination of electron-rich pyridines and trialkylphosphines is used as ligands. Alternatively, two or more of these ligands may also be combined in a molecule to form a chelating ligand.
  • a catalyst amount of from 0.001 mol% to 20 mol%, based on the nitrogen derivative, is used.
  • a catalyst amount of 0.01 mol% to 3 mol% is used.
  • the inventive method is carried out at temperatures of -20 ° C to 200 ° C, preferably at 50 ° C to 200 ° C and more preferably at 80 ° C to 120 ° C.
  • the process according to the invention can be carried out in the presence of a solvent or in bulk.
  • solvents of one of the starting materials pentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylenes, ethylbenzene, mesitylene, dioxane, tetrahydrofuran, diethyl ether, dibutyl ether, methyl t-butyl ether, diisopropyl ether, diethylene glycol dimethyl ether, methanol, Ethanol, propanol, isopropanol, methyl acetate, ethyl acetate, t-butyl acetate, dimethylformamide, diethylformamide, N-methylpyrrolidone, dimethylacetamide, dimethylsulfoxide, sulfolane, acetonitrile, propylene carbonate,
  • Aromatic hydrocarbons, amides, esters and ethers are preferably used.
  • the process according to the invention is preferably carried out in such a way that the solids are initially introduced and the liquid starting materials and the solvent are metered in.
  • the reaction mixture is preferably worked up by distillation and / or by extraction or crystallization after completion of the reaction.
  • Reaction conditions 0.50 mmol pyrrolidin-2-one, 1.00 mmol 1-hexyne, 0.01 mmol Ru source, 0.06 mmol ligand, toluene, 100 0 C, 15 h; a) GC yields with n-tetradecane as internal standard; b) diastereomer ratio according to GC;
  • the compound was prepared analogously to compound 3.2 of azetidin-2-one (1.3) (71.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way 3.3 (104 mg, 70% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.3: 4.3 was 2: 1.
  • the compound was prepared analogously to compound 3.2 from pipridin-2-one (1.4) (99.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.4 (165 mg, 70% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.4: 4.4 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from azepan-2-one (1.5) (113.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.5 (179 mg, 94% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.5: 4.5 was 30: 1.
  • Example 21 N - ((E) -hex-1-enyl) -azonane-2-one (3.6)
  • the compound was prepared analogously to compound 3.2 from azonan-2-one (1.6) (141.2 mg, 1.0 mmol) and 1-hexine (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / Ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.6 (186 mg, 86% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.6: 4.6 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from N-phenylacetamide (1.7) (135.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way, 3.7 (196 mg, 90% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.7: 4.7 was 30: 1
  • the compound was prepared analogously to compound 3.2 from N-methylbenzamide (1.8) (135.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, Gradient elution: 100/0 to 20/80)). In this way, 3.8 (98 mg, 46% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.8: 4.8 was 16: 1.
  • Example 24 ⁇ N- (4-Acetyl-phenyl) - ⁇ - ((E) -hex-1-enyl) -acetamide (3.9)
  • the compound was analogous to compound 3.2 from N- (4-acetyl-phenyl) -acetamide (1.9) (177.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). cleaned. In this way, 3.9 (84 mg, 33% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.9: 4.9 was 30: 1.
  • Example 25 N- (4-Ethoxy-phenyl) -N - ((E) -hex-1-enyl) -acetamide (3.10)
  • the compound was prepared analogously to compound 3.2 from N-methylformamide (1.12) (59.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way, 3.12 (110 mg, 83% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.12: 4.12 was 30: 1, rotamer ratio 3: 1.
  • the compound was prepared analogously to compound 3.2 from N-methylacetamide (1.13) (73.1 mg, 1.0 mmol) and 1 -hexine (B1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.13 (126 mg, 84% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.13: 4.13 was 30: 1, rotamer ratio 2: 1.
  • Example 27 ⁇ N - ((E) -Hex-1-enyl) ⁇ N- (isopropyl) acrylamide (3.14)
  • the compound was prepared analogously to compound 3.2 from N-rlsopropylacrylamide (1.14) (113.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.14 (74 mg, 38% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.14: 4.14 was 30: 1.
  • Example 28 1,4-Di - ((E) -hex-1-enyl) piperazine-2,5-dione (3.15)
  • the compound was prepared analogously to compound 3.2 from piperidine-2,5-dione (1.15) (114.1 mg, 1.0 mmol) and 1-hexyne (2.1) (458 ⁇ L, 4.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.15 (259.1 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.15: 4.15 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from imidazolidin-2-one (1.16).
  • Example 30 (4S, 5K) - ⁇ - ((E) -hex-enyl) -3,4- (dimethyl) -5-phenyl) imidazolidin-2-one
  • the compound was prepared analogously to compound 3.2 from I, 5 (S) -dimethyl-4 (R) -phenyl-imidazolidin-2-one (1.17) (190.3 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.17 (262 mg, 99% of theory) was used as colorless solid.
  • the diastereomer ratio (E: Z) 3.17: 4.17 was 23: 1.
  • Example 31 (2S) -N - ((E) -hex-enyl) -5- (oxo-pyrrolidine) -2-carboxylic acid methyl ester
  • the compound was prepared analogously to compound 3.2 from 5-oxopyrrolidin-2 (p ) - Carboxylic acid methyl ester (1.18) (143.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20 / 80). In this way, 3.18 (210.3 mg, 96% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.18: 4.18 was 6: 1.
  • the compound was prepared analogously to compound 3.2 from oxalidin-2-one (1.19) (87.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.19 (147.9 mg, 90.1% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.19: 4.19 was 23: 1.
  • Example 33 (4S) -3 - ((E) -hex-1-enyl) -4- (isopropyl) -oxazo-din-2-one (3.20)
  • Compound became analogous to compound 3.2 from 4 (S) -isopropyl-oxalidine 2-one (1.20) (129.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.20 (198.9 mg, 97% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.20: 4.20 was 30: 1.
  • Example 34 (4R, 5S) -3 - ((E) -hex-1-enyl) -5- (methyl) -4- (phenyl) oxazolidin-2-one (3.21)
  • the compound was analogous to compound 3.2 5 (S) -methyl-4 (R) -phenyl-oxalidin-2-one (1.21) (177.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.21 (211.1 mg, 84% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.21: 4.21 was 21: 1.
  • the compound was prepared analogously to compound 3.2 from pyrrolidine-2,5-dione (1.22) (99.1 mg, 1.0 mmol) and hexine (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way 4.22 (22 mg, 12% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.22: 4.22 was 1: 2 (according to GC). After column chromatography, only the Z-diastereomer was obtained.
  • Example 36 (2 ⁇ ) -3- (2-Oxopyrrolidin-1-yl) -propenoic acid methyl ester (3.23)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and methyl acrylate (2.2 ) (178 ⁇ L, 2.0 mmol) and purified by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.23 (211.1 mg, 84% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.23: 4.23 was 30: 1.
  • Example 37 ⁇ N - ((E) -3-Methoxy-prop-1-enyl) -pyrrolidin-2-one (3.24)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and 3-methoxy-propyne (2.3) (169 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to • 20/80). In this way 3.24 (145 mg, 93% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.24: 4.24 was 8: 1.
  • Example 38 ⁇ N - (( ⁇ ) -3,3-Dimethylbut-1-enyl) pyrrolidin-2-one (3.26)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L , 1.0 mmol) and 3,3-dimethyl-but-1-one (2.5) (246 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20 / 80). In this way 3.26 (161.8 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.26: 4.26 was 30: 1. -. ..
  • Example 39 N - ((E) -3-Methyl-1,3-di-1-enyl) pyrrolidin-2-one (3.27)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and 2-methyl-but-1-en-3-yn (2.6) (190 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, Gradierite elution: 100/0 until 20/80). In this way 3.27 (141.2 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.27: 4.27 was 24: 1. ,
  • Example 40 T $ - ((E) -2-trimethylsylvinyl) pyrrolidin-2-one (3.28)
  • the compound was prepared analogously to compound 3.1 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and ethynyl-trimethylsilane (2.7) (277 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.28 (120.0 mg, 70% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.28: 4.28 was 3: 1.
  • Example 41 ' N- ( ⁇ ) -2-phenyl-vinylpyrrolidin-2-one (3.29)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and phenylacetyene (2.8) (220 ⁇ L, 2.0 mmol) and by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.29 (180.0 mg, 99% of theory) was obtained as a grayish solid.
  • the diastereomer ratio (E: Z) 3.29: 4.29 was 22: 1.
  • Example 42 N - ((E) -4-Phenyl-but-1-enyl) pyrrolidin-2-one (3.30)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol and but-3-ynilbenzene (2.9) (281 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.30 (201.6 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.30: 4.30 was 30: 1.
  • Example 43 Yl - ((Z) -4-Phenyl-but-1-enyl) pyrrolidin-2-one (4.30)
  • the compound was prepared analogously to compound 4.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol and but-3-yn-benzene (2.9) (281 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 4.30 (198 mg, 92% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.30: 4.30 was 1: 8.
  • Example 44 1 $ - ((E) -dodeca-1,1-dienyl) pyrrolidin-2-one (3.31)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol). and dodec-1-en-II-in (2.10) (463 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.31 (241.1 mg, 99% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.31: 4.31 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and hept-l-en-6-yn (2.11) (188.3 mg, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.23 (170.3 mg, 95% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.32: 4.32 was 30: 1.
  • Example 46 N - ((E) -5-chloropent-1-enyl) pyrrolidin-2-one (3.33)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol and 5-chloro-pent-l-in (2.12) (212 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.33 (148 mg, 80% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.33: 3.43 was 30: 1.
  • Example 47 (2Z) -2- (2-oxopyrrolidin-1-yl) -3-phenylacrylic acid methyl ester (3.34)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and phenyl ethyl propionate (2.13) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.34 (154 mg, 63% of theory) was obtained as a yellowish solid.
  • the isomer ratio between the above-described compound and the other 3 isomers was 30: 1.

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  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne un procédé de production de composés de N-alcényle, consistant à faire réagir des composés N-H avec des alcynes terminales en présence de quantités catalytiques de complexes d'organyle et de ruthénium.
PCT/DE2005/002048 2004-11-24 2005-11-16 Procede d'addition d'amides, de carbamides, de lactames et de carbamates a des alcynes WO2006056166A2 (fr)

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WO2007026654A1 (fr) * 2005-08-29 2007-03-08 Kyoto University Énamide et son procédé de production, et diénamide et son procédé de production
WO2021122249A1 (fr) 2019-12-20 2021-06-24 Basf Se Synthèse de composés n-vinyliques par réaction de composés nh- cyliques avec de l'acétylène en présence d'un catalyseur homogène

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DE19838666A1 (de) * 1998-08-26 2000-03-02 Thomas Mueller Heterogenes Verfahren zur Herstellung von Enaminen, Iminen, Indolen und Diaminen aus Alkinen

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DE10001208B4 (de) * 2000-01-14 2005-02-03 Müller, Thomas, Dr. Verfahren zur homogen-katalytischen Hydroaminierung von Alkinen für die Herstellung von Enaminen, Iminen, Indolen und Diaminen und deren Weiterverarbeitung durch katalytische Hydrierung

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DE19838666A1 (de) * 1998-08-26 2000-03-02 Thomas Mueller Heterogenes Verfahren zur Herstellung von Enaminen, Iminen, Indolen und Diaminen aus Alkinen

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WATANABE, Y., ET AL.: "RUTHENIUM COMPLEX-CATALYSED ADDITION OF N-ARYL SUBSTITUTED AMIDES TO ALKYNES: NOVEL SYNTHESIS OF ENAMIDES" J. CHEM. SOC., CHEM. COMMUN., 1995, Seiten 413-414, XP009068309 in der Anmeldung erw{hnt *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007026654A1 (fr) * 2005-08-29 2007-03-08 Kyoto University Énamide et son procédé de production, et diénamide et son procédé de production
WO2021122249A1 (fr) 2019-12-20 2021-06-24 Basf Se Synthèse de composés n-vinyliques par réaction de composés nh- cyliques avec de l'acétylène en présence d'un catalyseur homogène
CN114829339A (zh) * 2019-12-20 2022-07-29 巴斯夫欧洲公司 通过使环状nh-化合物与乙炔在均相催化剂存在下反应而合成n-乙烯基化合物

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