Processes for the preparation of ortho-allylated hydroxy aryl compounds

Patent metadata

Field	Value
Publication number	US-11795127-B2
Application number	US-202217964347-A
Country	US
Kind code	B2
Filing date	Oct 12, 2022
Priority date	May 29, 2020
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

The present application describes process for preparing an ortho-allylated hydroxy aryl compounds such as compounds of Formula (I) by reacting an allylic alcohol with a hydroxy aryl compound in the presence of aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent wherein at least one carbon atom ortho to the hydroxy group in the hydroxy aryl compound is unsubstituted. The present application also includes compounds of Formula (I).

First claim

The invention claimed is:

1. 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 R 1 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 NR 6 , O and S, wherein the polycyclic ring system is optionally substituted with one or more substituents selected from ═O, OH, halo, C 1-16 alkyl, C 2-16 alkenyl, C 2-16 alkynyl, OC 1-16 alkyl, OC 2-16 alkenyl, OC 2-16 alkynyl; C 1-16 alkyleneOR 8 , C 2-16 alkenyleneOR 8 , C 2-16 alkynyleneOR 8 , C 6-18 aryl, C 3-18 cycloalkyl, C 3-18 heterocycloalkyl, and C 5-18 heteroaryl, the latter 4 groups being optionally substituted with one or more substituents selected from OH, halo, C 1-16 alkyl, OC 1-16 alkyl, and C 2-16 alkenyl;
when n is 3 or 4, further R 1 groups are independently selected from OH, halo, CN, NO 2 , COOH, C 2-16 alkenyl, C 2-16 alkynyl, C 3-18 cycloalkyl, C 1-16 alkyleneC 3-18 cycloalkyl, C 2-16 alkenyleneC 3-18 cycloalkyl, C 2-16 alkynyleneC 3-18 cycloalkyl, C 3-18 heterocycloalkyl, C 1-16 alkyleneC 3-18 heterocycloalkyl, C 1-10 alkenyleneC 3-18 heterocycloalkyl, C 2-16 alkynyleneC 3-18 heterocycloalkyl, C 6-18 aryl, C 1-16 alkyleneC 6-18 aryl, C 2-16 alkenyleneC 6-18 aryl, C 2-16 alkynyleneC 6-18 aryl, C 5-18 heteroaryl, C 2-16 alkyleneC 5-18 heteroaryl, C 2-16 alkenyleneC 5-18 heteroaryl, C 2-16 alkynyleneC 5-18 heteroaryl, Z—C 2-16 alkenyl, Z—C 2-16 alkynyl, Z—C 3-18 cycloalkyl, Z—C 1-16 alkyleneC 3-18 cycloalkyl, Z—C 2-16 alkenyleneC 3-18 cycloalkyl, Z—C 2-16 alkynyleneC 3-18 cycloalkyl, Z—C 3-18 heterocycloalkyl, Z—C 1-16 alkyleneC 3-18 heterocycloalkyl, Z—C 2-16 alkenyleneC 3-18 heterocycloalkyl, Z—C 2-16 alkynyleneC 3-18 heterocycloalkyl, Z—C 6-18 aryl, Z—C 1-16 alkyleneC 6-18 aryl, Z—C 2-16 alkenyleneC 6-18 aryl, Z—C 2-16 alkynyleneC 6-18 aryl, Z—C 5-18 heteroaryl, Z—C 1-16 alkyleneC 5-18 heteroaryl, Z—C 2-16 alkenyleneC 5-18 heteroaryl, and Z—C 2-16 alkynyleneC 5-18 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, C 1-16 alkyl, C 2-16 alkenyl, C 2-6 alkynyl, OC 1-16 alkyl, OC 2-16 alkenyl, and OC 2-16 alkynyl;
Z is selected from O, C(O), CO 2 , S, SO 2 , SO, and NR 7 ;
R 2 is H,
R 3 is selected from H and C 1-6 alkyl,
R 4 is selected from H, C 1-6 alkyl, C 6-18 aryl, C 1-16 alkyleneC 6-18 aryl, C 5-18 heteroaryl, and C 2-16 alkyleneC 5-18 heteroaryl;
R 5 is selected from H, C 2-26 alkenyl, C 2-26 alkynyl, C 3-18 cycloalkyl, C 1-16 alkyleneC 3-18 cycloalkyl, C 2-16 alkenyleneC 3-18 cycloalkyl, C 2-16 alkynyleneC 3-18 cycloalkyl, C 3-18 heterocycloalkyl, C 1-16 alkyleneC 3-18 heterocycloalkyl, C 1-16 alkenyleneC 3-18 heterocycloalkyl, C 2-16 alkynyleneC 3-18 heterocycloalkyl, C 6-18 aryl, C 1-16 alkyleneC 6-18 aryl, C 2-16 alkenyleneC 6-18 aryl, C 2-16 alkynyleneC 6-18 aryl, C 5-18 heteroaryl, C 2-16 alkyleneC 5-18 heteroaryl, C 2-16 alkenyleneC 5-18 heteroaryl, C 2-16 alkynyleneC 5-18 heteroaryl, wherein all cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from OH, NO 2 , CN, halo, C 1-16 alkyl, C 2-16 alkenyl, C 2-16 alkynyl, OC 1-16 alkyl, OC 2-16 alkenyl, OC 2-16 alkynyl, C 1-16 alkyleneOR 9 C 2-16 alkenyleneOR 9 , C 2-16 alkynyleneOR 9 , SO 3 C 1-16 alkyl, SO 3 C 6-16 aryl, and SO 3 C 5-18 heteroaryl substituted with C 1-16 alkyl; or
any two of R 2 , R 3 , R 4 and R 5 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 R 2 , R 3 , R 4 and R 5 are bonded, wherein the monocyclic or polycyclic ring system is optionally substituted with one or more substituents selected ═O, OH, halo, C 1-16 alkyl, C 2-16 alkenyl, C 2-16 alkynyl, OC 1-16 alkyl, OC 2-16 alkenyl, OC 2-16 alkynyl; C 1-16 alkyleneOR 8 , C 2-16 alkenyleneOR 8 , C 2-16 alkynyleneOR 8 , C 6-18 aryl, C 3-18 cycloalkyl, C 3-18 heterocycloalkyl, and C 5-18 heteroaryl, the latter 4 groups being optionally substituted with one or more substituents selected from OH, halo, C 1-16 alkyl, OC 1-16 alkyl, and C 2-16 alkenyl;
R 6 , R 7 , R 8 and R 9 are independently selected from H and C 1-6 alkyl; and
all alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, and heterocycloalkyl groups are optionally fluoro-substituted.

2. The process of claim 1 , wherein the non-protic solvent is a non-polar solvent or a polar aprotic solvent.

3. The process of claim 1 , wherein the aluminum compound is acidic alumina.

4. The process of claim 3 , wherein the process further comprises a dehydrating agent and/or an acid.

5. The process of claim 1 , wherein the polycyclic ring system is a gonanyl (steroid nucleus) which is optionally substituted with one or more substituents selected from OH, ═O, halo, C 1-16 alkyl, C 2-16 alkenyl, C 2-16 alkynyl, OC 1-16 alkyl, OC 2-16 alkenyl, OC 2-16 alkynyl, C 1-16 alkyleneOR 8 , C(O)C 1-16 alkyl, C(O)C 2-16 alkenyl, C(O)C 2-16 alkynyl, C 2-16 alkenyleneOR 8 , C 2-16 alkynyleneOR 8 , C 6-18 aryl, C 3-18 cycloalkyl, C 3-18 heterocycloalkyl, and C 5-18 heteroaryl, the latter 4 groups being optionally substituted with one or more substituents selected from OH, halo, C 1-16 alkyl, OC 1-16 alkyl, and C 2-16 alkenyl.

6. The process of claim 1 , wherein the polycyclic ring system is selected from benzofuranyl, isobenzofuranyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, benzepinyl, carbazolyl, and acridinyl which are optionally substituted with one or more substituents selected from OH, ═O, halo, C 1-16 alkyl, C 2-16 alkenyl, C 2-16 alkynyl, OC 1-16 alkyl, OC 2-16 alkenyl, OC 2-16 alkynyl, C(O)C 1-16 alkyl, C(O)C 2-16 alkenyl, C(O)C 2-16 alkynyl, C 1-16 alkyleneOR 8 , C 2-16 alkenyleneOR 8 , C 2-16 alkynyleneOR 8 , C 6-18 aryl, C 3-18 cycloalkyl, C 3-18 heterocycloalkyl, and C 5-18 heteroaryl, the latter 4 groups being optionally substituted with one or more substituents selected from OH, halo, C 1-16 alkyl, OC 1-16 alkyl, and C 2-16 alkenyl.

7. The process of claim 1 , wherein the polycyclic ring system is a benzofused ring system selected from benzofurochromenone, benzodiozinyl, benzodiozolyl, indenyl, indolinyl, chromenyl, dihydrochromenonyl, chromenonyl, chromanonyl, benzoxazinyl, quinolinonyl, isoquinolinonyl and coumarinyl which are optionally substituted with one or more substituents selected from OH, ═O, halo, C 1-16 alkyl, C 2-16 alkenyl, C 2-16 alkynyl, OC 1-16 alkyl, OC 2-16 alkenyl, OC 2-16 alkynyl, C 1-16 alkyleneOR 8 , C 2-16 alkenyleneOR 8 , C 2-16 alkynyleneOR 8 , C 6-18 aryl, C 3-18 cycloalkyl, C 3-18 heterocycloalkyl, and C 5-18 heteroaryl, the latter 4 groups being optionally substituted with one or more substituents selected from OH, halo, C 1-16 alkyl, OC 1-16 alkyl, and C 2-16 alkenyl.

8. The process of claim 1 ,

Assignees

• Univ Mcmaster

Inventors

• Magolan Jakob
• Jentsch Nicholas
• Zhang Xiong
• Piotrowski Mathew
• Darveau Patrick
• Fragis Meghan
• Johnson Jarrod
• Ritchie Nicole
• Kaul Arnav

Classifications

• C07C37/14 Primary

  by addition reactions, i.e. reactions involving at least one carbon-to-carbon unsaturated bond · CPC title

• B01J21/04

  Alumina · CPC title

• C07C41/26

  by introduction of hydroxy or O-metal groups · CPC title

• C07C201/12

  by reactions not involving the formation of nitro groups · CPC title

• C07C253/30

  by reactions not involving the formation of cyano groups · CPC title