Method of producing macrocyclic ketone, and intermediate thereof

A method of producing optically active muscone represented by Formula (I-a):

• the method comprising:
• reacting 2-cyclopentadecenones represented by General Formula (III):
• wherein the wavy line represents a cis isomer and/or a trans isomer of double bond, with an organic metal methylation reagent via 1,4-conjugation addition reaction in the presence of a copper or nickel catalyst, an enol anion scavenger, and an optically active ligand to give an optically active 3-methyl-1-cyclopentadecene derivative represented by General Formula (II-a):
• wherein R represents a straight- or branched-chain acyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyloxycarbonyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyl group which may have a substituent containing a heteroatom or an aromatic ring;* represents an asymmetric carbon atom;
• and the wavy line is the same as that above;
• and
• solvolyzing the enol moiety of the optically active 3-methyl-1-cyclopentadecene derivative.

A method of producing optically active muscone represented by Formula (I-a):

• the method comprising solvolyzing an enol moiety of an optically active 3-methyl-1-cyclopentadecene derivative represented by General Formula (II-a):
• wherein R represents a straight- or branched-chain acyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyloxycarbonyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyl group which may have a substituent containing a heteroatom or an aromatic ring;
• * represents an asymmetric carbon atom;
• and the wavy line represents a cis isomer and/or a trans isomer of double bond.

A method of producing optically active muscone represented by Formula (I-a):

• the method comprising:
• reacting 2-cyclopentadecenones represented by General Formula (III):
• wherein the wavy line represents a cis isomer and/or a trans isomer of double bond, with an organic metal methylation reagent via 1, 4-conjugation addition reaction in the presence of a copper or nickel catalyst, an enol anion scavenger, and an optically active ligand to give an optically active 3-methyl-1-cyclopentadecene derivative represented by General Formula (II-a):
• wherein R represents a straight- or branched-chain acyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyloxycarbonyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyl group which may have a substituent containing a heteroatom or an aromatic ring, or a straight- or branched-chain silyl group which may have a substituent containing a heteroatom or an aromatic ring;
• * represents an asymmetric carbon atom;
• and the wavy line is the same as that above;
• and
• solvolyzing the enol moiety of the optically active 3-methyl-1-cyclopentadecene derivative, wherein the optically active ligand is an optically active ligand represented by General Formula (IV):
• wherein Cn represents a substituted or unsubstituted group having 2 to 4 carbon atoms, which forms a ring together with two oxygen atoms and a phosphorus atom;
• and R1 and R2 each independently represents a hydrogen atom or a chain or cyclic alkyl, aryl, alkanoyl or aralkyl group that may be substituted with a substituent or R1 and R2 represent groups that can form a heterocyclic ring together with an nitrogen atom connected thereto.

A method of producing optically active muscone represented by Formula (I-a):

• the method comprising:
• reacting 2-cyclopentadecenones represented by General Formula (III):
• wherein the wavy line represents a cis isomer and/or a trans isomer of double bond, with an organic metal methylation reagent via 1, 4-conjugation addition reaction in the presence of a copper or nickel catalyst, an enol anion scavenger, and an optically active ligand to give an optically active 3-methyl-1-cyclopentadecene derivative represented by General Formula (II-a):
• wherein R represents a straight- or branched-chain acyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyloxycarbonyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyl group which may have a substituent containing a heteroatom or an aromatic ring, or a straight- or branched-chain silyl group which may have a substituent containing a heteroatom or an aromatic ring;
• * represents an asymmetric carbon atom;
• and the wavy line is the same as that above;
• and
• solvolyzing the enol moiety of the optically active 3-methyl-1-cyclopentadecene derivative, wherein the optically active ligand is an optically active ligand represented by General Formula (V):
• wherein, Cn represents a substituted or unsubstituted group having 2 to 4 carbon atoms, which forms a ring together with two oxygen atoms and a phosphorus atom;
• and R3 represents a hydrogen atom or a chain or cyclic alkyl, aryl, alkanoyl or aralkyl group that may be substituted with a substituent.

A method of producing optically active muscone represented by Formula (I-a):

• the method comprising:
• reacting 2-cyclopentadecenones represented by General Formula (III):
• wherein the wavy line represents a cis isomer and/or a trans isomer of double bond, with an organic metal methylation reagent via 1, 4-conjugation addition reaction in the presence of a copper or nickel catalyst, an enol anion scavenger, and an optically active ligand to give an optically active 3-methyl-1-cyclopentadecene derivative represented by General Formula (II-a)
• wherein R represents a straight- or branched-chain acyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyloxycarbonyl group which may have a substituent containing a heteroatom or an aromatic ring, a straight- or branched-chain alkyl group which may have a substituent containing a heteroatom or an aromatic ring, or a straight- or branched-chain silyl group which may have a substituent containing a heteroatom or an aromatic ring;
• * represents an asymmetric carbon atom;
• and the wavy line is the same as that above;
• and
• solvolyzing the enol moiety of the optically active 3-methyl-1-cyclopentadecene derivative, wherein the optically active ligand is 4-(cis-2, 6-dimethylpiperidine)-(R)-ditetrahydronaphthodioxaphosphepin, 4-(cis-2, 6-dimethylpiperidine-(R)-dinaphthodioxaphosphepin, 4-((R, R)-2, 5-diphenylpyrrolidine)-(R)-dinaphthodioxaphosphepin, or 4-((R, R)-2, 5-diphenylpyrrolidine)-(R)-ditetrahydronaphtho-dioxaphosphepin.