Processes for the preparation of ortho-allylated hydroxy aryl compounds

A process for preparing a compound of Formula (I) comprising:

• reacting a compound of Formula (II)
• with a compound of Formula (III)
• in the presence of an aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent to form the compound of Formula (I),
• wherein:
• n is 2, 3 or 4;
• two R1 groups are linked together to form a polycyclic ring system having 8 or more atoms together with the phenyl ring to which said groups are bonded, and in which one or more carbon atoms in said polycyclic ring system is optionally replaced with a heteromoiety selected from NR6, O and S, wherein the polycyclic ring system is optionally substituted with one or more substituents selected from ═O, OH, halo, C1-16alkyl, C2-16alkenyl, C2-16alkynyl, OC1-16alkyl, OC2-16alkenyl, OC2-16alkynyl;
• C1-16alkyleneOR8, C2-16alkenyleneOR8, C2-16alkynyleneOR8, C6-18 aryl, C3-18 cycloalkyl, C3-18heterocycloalkyl, and C5-18heteroaryl, the latter 4 groups being optionally substituted with one or more substituents selected from OH, halo, C1-16alkyl, OC1-16alkyl, and C2-16alkenyl;
• when n is 3 or 4, further R1 groups are independently selected from OH, halo, CN, NO2, COOH, C2-16alkenyl, C2-16alkynyl, C3-18cycloalkyl, C1-16alkyleneC3-18cycloalkyl, C2-16alkenyleneC3-18 cycloalkyl, C2-16alkynyleneC3-18cycloalkyl, C3-18heterocycloalkyl, C1-16alkyleneC3-18heterocycloalkyl, C1-10alkenyleneC3-18heterocycloalkyl, C2-16alkynyleneC3-18heterocycloalkyl, C6-18 aryl, C1-16alkyleneC6-18 aryl, C2-16alkenyleneC6-18 aryl, C2-16alkynyleneC6-18aryl, C5-18heteroaryl, C2-16alkyleneC5-18heteroaryl, C2-16alkenyleneC5-18heteroaryl, C2-16alkynyleneC5-18 heteroaryl, Z—C2-16alkenyl, Z—C2-16alkynyl, Z—C3-18 cycloalkyl, Z—C1-16alkyleneC3-18cycloalkyl, Z—C2-16alkenyleneC3-18cycloalkyl, Z—C2-16alkynyleneC3-18 cycloalkyl, Z—C3-18heterocycloalkyl, Z—C1-16alkyleneC3-18 heterocycloalkyl, Z—C2-16alkenyleneC3-18heterocycloalkyl, Z—C2-16alkynyleneC3-18heterocycloalkyl, Z—C6-18aryl, Z—C1-16alkyleneC6-18aryl, Z—C2-16alkenyleneC6-18aryl, Z—C2-16alkynyleneC6-18aryl, Z—C5-18heteroaryl, Z—C1-16alkyleneC5-18 heteroaryl, Z—C2-16alkenyleneC5-18 heteroaryl, and Z—C2-16alkynyleneC5-18 heteroaryl, wherein all alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl heterocycloalkyl, aryl, and heteroaryl groups are optionally substituted with one or more substituents selected from OH, halo, C1-16alkyl, C2-16alkenyl, C2-6alkynyl, OC1-16alkyl, OC2-16alkenyl, and OC2-16alkynyl;
• Z is selected from O, C(O), CO2, S, SO2, SO, and NR7;
• R2 is H,
• R3 is selected from H and C1-6alkyl,
• R4 is selected from H, C1-6alkyl, C6-18aryl, C1-16alkyleneC6-18aryl, C5-18 heteroaryl, and C2-16alkyleneC5-18 heteroaryl;
• R5 is selected from H, C2-26alkenyl, C2-26alkynyl, C3-18 cycloalkyl, C1-16alkyleneC3-18cycloalkyl, C2-16alkenyleneC3-18 cycloalkyl, C2-16alkynyleneC3-18 cycloalkyl, C3-18heterocycloalkyl, C1-16alkyleneC3-18 heterocycloalkyl, C1-16alkenyleneC3-18heterocycloalkyl, C2-16alkynyleneC3-18 heterocycloalkyl, C6-18aryl, C1-16alkyleneC6-18aryl, C2-16alkenyleneC6-18aryl, C2-16alkynyleneC6-18aryl, C5-18heteroaryl, C2-16alkyleneC5-18heteroaryl, C2-16alkenyleneC5-18 heteroaryl, C2-16alkynyleneC5-18 heteroaryl, wherein all cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from OH, NO2, CN, halo, C1-16alkyl, C2-16alkenyl, C2-16alkynyl, OC1-16alkyl, OC2-16alkenyl, OC2-16alkynyl, C1-16alkyleneOR9 C2-16alkenyleneOR9, C2-16alkynyleneOR9, SO3C1-16alkyl, SO3C6-16aryl, and SO3C5-18heteroaryl substituted with C1-16alkyl;
• or
• any two of R2, R3, R4 and R5 are linked together to form an unsubstituted or substituted monocyclic or polycyclic ring system having 4 or more atoms together with the carbon atoms to which said any two of R2, R3, R4 and R5 are bonded, wherein the monocyclic or polycyclic ring system is optionally substituted with one or more substituents selected ═O, OH, halo, C1-16alkyl, C2-16alkenyl, C2-16alkynyl, OC1-16alkyl, OC2-16alkenyl, OC2-16alkynyl;
• C1-16alkyleneOR8, C2-16alkenyleneOR8, C2-16alkynyleneOR8, C6-18aryl, C3-18 cycloalkyl, C3-18heterocycloalkyl, and C5-18heteroaryl, the latter 4 groups being optionally substituted with one or more substituents selected from OH, halo, C1-16alkyl, OC1-16alkyl, and C2-16alkenyl;
• R6, R7, R8 and R9 are independently selected from H and C1-6alkyl;
• and
• all alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, and heterocycloalkyl groups are optionally fluoro-substituted.