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1. A method for catalytic asymmetric synthesis of an optically active isoxazoline compound, the method comprising:
causing an α,β-unsaturated carbonyl compound of Formula (1): where R1a is C1-6 fluoroalkyl or C3-8 fluorocycloalkyl; each of A1a, A2a, A3a, and A4a is independently C—Ya; each of A5a, A6a, and A7a is independently C—Xa; Xa is a hydrogen atom, a halogen atom, cyano, nitro, —SF5, C1-6 alkyl, C1-6 haloalkyl, hydroxy(C1-6)haloalkyl, C1-6 alkoxy(C1-6)haloalkyl, C1-6 haloalkoxy(C1-6)haloalkyl, C3-8 halocycloalkyl, —OR2a, —OSO2R2a, or —S(O)rR2a, and Xas are optionally the same as or different from each other; R2a is C1-6 alkyl, C1-4 alkoxy(C1-4)alkyl, C1-6 haloalkyl, or C1-3 haloalkoxy(C1-3)haloalkyl; Ya is a hydrogen atom, a halogen atom, cyano, nitro, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, N(R4a)R3a Yas are optionally the same as or different from each other, and when two Yas are adjacent to each other, the two Yas optionally form a 6-membered ring together with carbon atoms to which the two Yas are respectively bonded, by forming -A8a=A9a-A10a=A11a-; each of A8a, A9a, A10a, and A11a is independently N or C—Y1a; Y1a is a hydrogen atom, a halogen atom, cyano, nitro, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, N(R4a)R3a, and Y1as are optionally the same as or different from each other; R3a is C1-6 alkyl, C1-6 alkylcarbonyl, C1-6 haloalkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylthiocarbonyl, C1-6 alkoxythiocarbonyl, C1-6 alkyldithiocarbonyl, C1-6 alkylsulfonyl, or C1-6 haloalkylsulfonyl; R4a is a hydrogen atom or C1-6 alkyl; R5a is —C(O)NH2, —C(O)NHR6a, —C(S)NHR6a, or -L-NHR6a; R6a is C1-6 alkyl, C1-6 alkyl optionally substituted with R9a, C3-6 cycloalkyl optionally condensed with a benzene ring, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, —N(R11a)R10a, —C(O)OR12a, —C(O)NH2, —C(O)NHR12a, —C(R14a)═NOR13a, phenyl, phenyl substituted with (Z)p1, D-5, D-7, D-10, D-11, D-12, D-14, D-15, D-18, D-31, D-32, D-42, D-43, D-45, D-46, D-48, E-1, E-2, E-3, E-4, E-7, E-9 to E-20 or E-21; R9a is a halogen atom, cyano, amino, C3-6 cycloalkyl, C3-6 halocycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, —C(O)R15a, —C(O)OR15a, —C(O)NH2, —C(O)N(R16a)R15a, —C(S)NH2, —C(S)N(R16a)R15a, —C(R18a)═NOR17a, phenyl, phenyl substituted with (Z)p1, D-1 to D-50, or E-1 to E-21; D-1 to D-50 are heteroaromatic rings of structural formulae below: Z is a halogen atom, cyano, nitro, amino, C1-6 alkyl, (C1-6)alkyl optionally substituted with R19a, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, C1-6 alkoxycarbonyl, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —C(O)N(R21a)R20a, —C(S)N(R21a)R20a, C1-6 alkylaminosulfonyl, or di(C1-6 alkyl)aminosulfonyl, and when p1, p2, p3, or p4 is an integer of 2 or more, Zs are optionally the same as or different from each other; E-1 to E-21 are heterocycles of structural formulae below: Z1 is a hydrogen atom, C1-6 alkyl, C3-6 cycloalkyl, benzyl, (C1-6)alkyl optionally substituted with R19a, C1-6 haloalkyl, C1-6 alkylcarbonyl, C1-6 haloalkylcarbonyl, phenylcarbonyl, phenylcarbonyl substituted with (Z)p1, C1-6 alkoxycarbonyl, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —C(O)N(R21a)R20a, C(S)N(R21a)R20a, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, E-17, or E-18; Z2 is a hydrogen atom or C1-6 haloalkylcarbonyl; R10a is a C1-6 haloalkyl, —C(O)R15a, —C(O)OR15a, phenyl, phenyl substituted with (Z)p1, D-3, D-4, D-18, D-42, D-45, D-46, D-48, or D-49; R11a is a hydrogen atom, C1-6 alkyl, or C3-6 alkynyl; R12a is C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy(C1-4)alkyl, C1-6 alkylthio(C1-4)alkyl, C3-8 cycloalkyl, C3-6 alkenyl, or C3-6 alkynyl; R13a is a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 halocycloalkyl, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, C3-6 haloalkynyl, phenyl, phenyl substituted with (Z)p1, D-42, D-45 to D-49, E-1 to E-4, or E-7; R14a is a hydrogen atom, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy(C1-6)alkyl, C1-6 alkylthio(C1-6)alkyl, C3-6 cycloalkyl, or phenyl; R15a is C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl(C1-4)alkyl, C3-6 cycloalkyl, C1-6 alkoxy(C1-6)alkyl, hydroxy(C1-6)alkyl, phenyl, phenyl substituted with R24a, C3-6 haloalkenyl, C3-6 alkenyl, or C3-6 alkynyl; R24a is a halogen atom, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, C1-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, C1-6 alkoxycarbonyl, —C(O)NH2, —S(O)2NH2, C1-6 alkylaminosulfonyl, or di(C1-6 alkyl)aminosulfonyl; R16a is a hydrogen atom or C1-6 alkyl; R19a is hydroxy, C1-4 alkoxy, or C1-4 alkylthio; R20a is a hydrogen atom, C1-6 alkyl, C3-6 cycloalkyl, C3-6 alkenyl, C3-6 haloalkenyl, C3-6 alkynyl, —C(R17a)═NOR18a, —C(O)OR18a, —C(O)NH2, —C(O)N(R17a)R18a, —C(O)NHC(O)R18a, —C(O)N(R17a)C(O)OR18a, —N(R26a)R25a, or phenyl; R17a is a hydrogen atom or C1-6 alkyl; R18a is C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkenyl; R21a is a hydrogen atom, C1-6 alkyl, or C3-6 alkynyl; R22a is C1-6 alkyl, phenyl, or phenyl substituted with (Z)p1; R23a is C1-4 alkyl, and when q2, q3, or q4 is an integer of 2 or more, R23as are optionally the same as or different from each other, and further, when two of R23as exist on a single carbon atom as substituents, the two R23as optionally form an oxo together; R25a is C1-6 haloalkyl, C1-6 alkoxycarbonyl, phenyl, phenyl substituted with R27a, D-42 to D-46 or D-47; R27a is a halogen atom, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, or C1-6 alkylsulfonyl; R26a is a hydrogen atom, C1-6 alkyl, C3-6 alkenyl, or C3-6 alkynyl, p1 is an integer of 1 to 5; p2 is an integer of 0 to 4; p3 is an integer of 0 to 3; p4 is an integer of 0 to 2; p5 is an integer of 0 or 1; q2 is an integer of 0 to 5; q3 is an integer of 0 to 7; q4 is an integer of 0 to 9; t is an integer of 0 or 1; L is —C(R7a)(R8a)—, —C(R7a)(R8a)CH2—, or —CH2C(R7a)(R8a)—; R7a is a hydrogen atom, cyano, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxycarbonyl, —C(O)NH2, or —C(S)NH2; R8a is a hydrogen atom or C1-6 alkyl, or optionally forms a 3 to 6-membered ring together with carbon atoms bonded to a C2-5 alkylene chain formed by R7a and R8a, in which the alkylene chain optionally contains 1 to 3 oxygen atom(s), sulfur atom(s), or nitrogen atom(s); and r is an integer of 0 to 2,to react with a hydroxyl amine in a solvent, in the presence of a base and a chiral phase transfer catalyst of Formulae (7), (8), (9), or (10): where X1b− is a negatively charged ion, wherein the optically active isoxazoline compound is represented by Formula (6): where each of R1a, R5a, Xa, A1a, A2a, A3a, A4a, A5a, A6a, and A7a is the same as that described above. |
