Methylation or ethylation agent and process for 1,4-addition of a methyl or ethyl group to an .alpha., .beta.-unsaturated keto compound

A combination of a compound to be alkylated and a methylation or ethylation agent comprising an aluminum reagent Alk.sub.3-n AlOEt.sub.n as a source of methyl or ethyl, wherein Alk is methyl or ethyl, OEt is ethoxy, and n is 1 or 2, and 1-10 mole % per mole of compound to be alkylated of one or more copper compound selected from the group consisting of:

• a) copper (I) compounds of formula I;
• b) copper (II) compounds of formula I,
• CuX or CuX.sub.2 (I)
• wherein X is a monovalent radical and stands for chlorine, bromine, iodine, cyano, thienyl, phenyl, alkoxy of 1 to 8 carbon atoms optionally branched and/or unsaturated, thioalkoxy wherein the alkyl radical has 1-8 carbon atoms and is optionally branched and/or unsaturated, a substituted alkinyl radical R--C.tbd.C-- (wherein R is phenyl or an optionally branched C.sub.1 -C.sub.8 -alkyl radical), an inorganic acid radical, a carboxylic acid, or a bidentate complex ligand coordinated by oxygen atoms, nitrogen atoms or both, excluding the ligand acetylacetonate in the case of the divalent coppers;
• c) compounds of formula II
• Cu.sub.2 Y or CuY (II)
• wherein Y is a divalent radical and stands for oxygen or sulfur;
• and d) combinations thereof.

A methylation or ethylation agent comprising a compound selected from the group consisting of trimethyl aluminum, dimethyl zinc and triethyl aluminum as a source of methyl or ethyl, and one or more copper compounds selected for the group consisting of:

• a) copper (I) compounds of formula I;
• b) copper (II) compounds of formula I
• CuX or CuX.sub.2 (I)
• wherein X is a monovalent radical and stands for chlorine, bromine, iodine, cyano, thienyl, phenyl, alkoxy of 1 to 8 carbon atoms optionally branched and/or unsaturated, thioalkoxy wherein the alkyl radical has 1-8 carbon atoms and is optionally branched and/or unsaturated, a substituted alkinyl radical R--C.tbd.C-- (wherein R is phenyl or an optionally branched C.sub.1 -C.sub.8 -alkyl radical), an inorganic acid radical, a carboxylic acid, or a bidentate complex ligand coordinated by oxygen atoms, nitrogen atoms or both, excluding the ligand acetylacetonate in the case of the divalent coppers;
• c) compounds of formula II
• Cu.sub.2 Y or CuY (II)
• wherein Y is a divalent radical and stands for oxygen or sulfur;
• and d) combinations thereof,
• wherein said agent additionally contains up to 1 mol % of nickel salt(s).

A process for 1-4-addition of a methyl or ethyl group of an .alpha.,.beta.-unsaturated, an .alpha.,.beta.-double unsaturated ketone or an .alpha.,.beta.-unsaturated aldehyde, comprising alkylating said .alpha.,.beta.-unsaturated ketone, .alpha.,.beta.-double unsaturated ketone or the .alpha.,.beta.-unsaturated aldehyde with a methylation of ethylation agent comprising a compound selected from the group consisting of aluminum trimethyl, zinc dimethyl and aluminum triethyl in the presence of a catalytic amount of one or more copper compounds selected from the group consisting of:

• a) copper (I) compounds of formula I;
• b) copper (II) compounds or formula I,
• CuX or CuX.sub.2 (I)
• wherein X is a monovalent radical and stands for chlorine, bromine, iodine, cyano, thienyl, phenyl, an alkoxy of 1 to 8 carbon atoms optionally branched and/or unsaturated, thioalkoxy wherein the alkyl radical has 1-8 carbon atoms and is optionally branched and/or unsaturated, a substituted alkinyl radical R--C.tbd.C-- (wherein R is phenyl or an optionally branched C.sub.1 -C.sub.6 -alkyl radical), an inorganic acid radical, a carboxylic acid, or a bidentate complex ligand coordinated by oxygen atoms, nitrogen atoms or both, excluding the ligand acetylacetonate in the case of the divalent coppers;
• c) compounds of formula II
• Cu.sub.2 Y or CuY (III)
• wherein Y is a divalent radical and stands for oxygen or sulfur;
• and d) combinations thereof.

A process for 1,4-addition of a methyl or ethyl group to an .alpha.,.beta.-unsaturated, an .alpha.,.beta.-double unsaturated ketone or an .alpha.,.beta.-unsaturated aldehyde, comprising alkylating said .alpha.,.beta.-unsaturated ketone, .alpha.,.beta.-double unsaturated ketone, or .alpha.,.beta.-unsaturated aldehyde in the presence of a catalytic amount of a methylation or ethylation agent comprising an aluminum reagent Alk.sub.3-n AlOEt.sub.n as a source of methyl or ethyl, wherein Alk is methyl or ethyl, OEt is ethoxy, and n is 1 or 2, and a catalytic amount of one or more copper compounds selected from the group consisting of:

• a) copper (I) compounds of formula (I);
• b) copper (II) compounds of formula I
• CuX or CuX.sub.2 (I)
• wherein X is a monovalent radical and stands for chlorine, bromine, iodine, cyano, thienyl, phenyl, alkoxy of 1 to 8 carbon atoms optionally branched and/or unsaturated, thioalkoxy wherein the alkyl radical has 1-8 carbon atoms and is optionally branched and/or unsaturated, a substituted alkinyl radical R--C.tbd.C-- (wherein R is phenyl or an optionally branched C.sub.1 -C.sub.8 -alkyl radical), an inorganic acid radical, a carboxylic acid, or a bidentate complex ligand coordinated by oxygen atoms, nitrogen atoms or both, excluding the ligand acetylacetonate in the case of the divalent coppers;
• c) compounds of formula II
• Cu.sub.2 Y or CuY (II)
• wherein Y is a divalent radical and stands for oxygen or sulfur;
• and d) combination thereof.

A process for production of a 3-acyloxy-1.alpha.-methyl-androsta-2,4-dien-17-one, comprising the step of methylating androsta-1,4-diene-3,17-dione to from an intermediate wherein methlylation is achieved with a compound selected from the group consisting of aluminum trimethyl, zinc dimethyl and aluminum triethyl in the presence of a catalytic amount of one or more copper compounds selected from the group consisting of:

• a) copper (I) compounds of formula I;
• b) copper (II) compounds of formula I
• CuX or CuX.sub.2 (I)
• wherein X is a monovalent radical and stands for chlorine, bromine, iodine, cyano, thienyl, phenyl, an alkoxy of 1 to 8 carbon atoms optionally branched and/or unsaturated, thioalkoxy wherein the alkyl radical has 1-8 carbon atoms and is optionally branched and/or unsaturated, a substituted alkinyl radical R--C.tbd.C-- (wherein R is phenyl or an optionally branched C.sub.1 -C.sub.8 -alkyl radical), an inorganic acid radical, a carboxylic acid, or a bidentate complex ligand coordinated by oxygen atoms, nitrogen atoms, or both excluding the ligand acetylacetonate in the case of the divalent coppers;
• c) compounds of formula II
• Cu.sub.2 Y or CuY (II)
• wherein Y is a divalent radical and stands for oxygen or sulfur;
• and d) combinations thereof, and trapping after the methylation, the enolate present in the reaction mixture with a carboxylic acid anhydride or chloride of a straight or branched chain alkane carboxylic acid with 2-8 carbon atoms or benzoic acid.

A process for 1,4-addition of a methyl or ethyl group to an .alpha.,.beta.-unsaturated an .alpha.,.beta.-double unsaturated ketone or an .alpha.,.beta.-unsaturated aldehyde, comprising alkylating said .alpha.,.beta.-unsaturated ketone, .alpha.,.beta.-double unsaturated ketone, or .alpha.,.beta.-unsaturated aldehyde with a methylation or ethylation agent comprising a compound selected from the group consisting of:

• trimethyl aluminum, dimethyl zinc and triethyl aluminum as a source of methyl or ethyl, and one or more compounds selected from the group consisting of:
• a) copper (I) compounds of formula I;
• b) copper (II) compounds of formula I
• CuX or CuX.sub.2 (I)
• wherein X is a monovalent radical and stands for chlorine, bromine, iodine, cyano, thienyl, phenyl, alkoxy of 1 to 8 carbon atoms optionally branched and/or unsaturated, thioalkoxy wherein the alkyl radical has 1-8 carbon atoms and is optionally branched and/or unsaturated, a substituted alkinyl radical R--C.tbd.C-- (wherein R is phenyl or an optionally branched C.sub.1 -C.sub.8 -alkyl radical), an inorganic acid radical, a carboxylic acid, or a bidentate complex ligand coordinated by oxygen and/or nitrogen atoms, excluding the ligand acetylacetonate in the case of the divalent coppers;
• c) compounds of formula II
• Cu.sub.2 Y or CuY (II)
• wherein Y is a divalent radical and stands for oxygen or sulfur d) combinations thereof wherein alkylation is performed with a combination of compounds of formula I and compounds of formula II.