Iron catalyzed highly enantioselective cis-dihydroxylation of quinones

Patent metadata

Field	Value
Publication number	US-12281065-B2
Application number	US-202318155431-A
Country	US
Kind code	B2
Filing date	Jan 17, 2023
Priority date	Jan 17, 2022
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

Methods for asymmetric cis-dihydroxylation (“AD”) of quinones to produce cis-diols of quinones with high yield (i.e. a yield ≥30%) and high enantioselectivity (i.e. an enantiometric excess ≥30%) are disclosed. The method uses an iron-based catalyst, such as one or more Fe(II) complexes, as the catalyst, and can be performed under mild reaction conditions (e.g. a temperature ≤50° C. at 1 atom in open air). The method generally includes: (i) maintaining a reaction mixture at a temperature for a period of time sufficient to form a product, where the reaction mixture contains a quinone, one or more iron-based catalyst(s), and a solvent, and where the product contains a chiral cis-diol. Optionally, the method also includes adding an oxidant into the reaction mixture prior to and/or during step (i), such as a hydrogen peroxide solution.

First claim

We claim:

1. A method for asymmetric cis-dihydroxylation of a quinone comprising:
(i) maintaining a reaction mixture at a temperature for a period of time sufficient to form a product,
wherein the reaction mixture comprises the quinone, one or more iron-based catalyst(s), and a solvent,
wherein the product comprises a cis-diol,
wherein the one or more iron-based catalyst(s) have the structure of:

or a stereoisomer thereof,
wherein:
(a) L 1 is

 each occurrence of T′ is an unsubstituted C6 monocyclic group and p is 1;
(b) R 18 and R 18 ′ are independently a substituted or unsubstituted C1-C6 alkyl;
(c) R 19 is an unsubstituted methylene:
(d) R 23 and R 23 ′ are hydrogen;
(e) R 24 and R 24 ′ are independently unsubstituted C1-C2 alkyl;
(d) R 25 and R 25 ′ are independently a triflate or halide; and
(e) the substituents, when present, are independently a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a carbonyl, a halide, a hydroxyl, an aroxy, an alkylthio, an arylthio, a cyano, an isocyano, an alkoxyl, a nitro, a carboxyl, an amino, an amido, an oxo, a silyl, a sulfinyl, a sulfonyl, a sulfonic acid, a phosphonium, a phosphanyl, a phosphoryl, a phosphonyl, or a thiol, or a combination thereof; and
wherein the cis-diol has an enantiomeric excess from about 80% to 100%, as determined by chiral HPLC.

2. The method of claim 1 further comprising adding an oxidant into the reaction mixture prior to and/or during step (i).

3. The method of claim 2 , wherein the total mole amount of the oxidant in the reaction mixture is in a range from about 1-time to about 10-time of the total mole amount of the quinone.

4. The method of claim 1 , wherein the quinone has a structure of:

wherein:
(a) R 1 -R 4 are independently a hydrogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted aryl, a substituted or unsubstituted polyaryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heteropolyaryl, a substituted or unsubstituted cyclic group, a substituted or unsubstituted heterocyclic, a substituted or unsubstituted aralkyl, a halide, a hydroxyl, an alkoxyl, an amino, an amido, an aminocarbonyl, a carbonyl, a nitrile, or a thiol, or two neighboring R groups together with the carbon atoms to which they are attached form a substituted or unsubstituted aryl, a substituted or unsubstituted polyaryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heteropolyaryl, a substituted or unsubstituted cyclic group, or a substituted or unsubstituted heterocyclic group; and
(b) the substituents, when present, are independently a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted cyclic group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted polyaryl, a substituted or unsubstituted polyheteroaryl, a substituted or unsubstituted aralkyl, a carbonyl, a halide, a hydroxyl, a phenoxy, an aroxy, an alkylthio, a phenylthio, an arylthio, a cyano, an isocyano, an alkoxyl, a nitro, a carboxyl, an amino, an amido, an oxo, a silyl, a sulfinyl, a sulfonyl, a sulfonic acid, a phosphonium, a phosphanyl, a phosphoryl, a phosphonyl, or a thiol, or a combination thereof.

5. The method of claim 4 , wherein at least one of R 1 -R 4 , at least two of R 1 -R 4 , or at least three of R 1 -R 4 is an or are electron-donating group(s).

6. The method of claim 4 , wherein at least one of R 1 -R 4 is hydrogen.

7. The method of claim 4 , wherein R 1 -R 4 are independently a hydrogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted polyaryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heteropolyaryl, a substituted or unsubstituted cyclic group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aralkyl, an alkoxyl, or a carbonyl, or two neighboring R groups form a substituted or unsubstituted aryl, a substituted or unsubstituted polyaryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heteropolyaryl, a substituted or unsubstituted cyclic group, or a substituted or unsubstituted heterocyclic group.

8. The method of claim 4 , wherein R 1 -R 4 are independently a hydrogen, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cyclic group, a substituted or unsubstituted heterocyclic group, an alkoxyl, or

 R 5 is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted polyaryl, a substituted or unsubstituted heteropolyaryl, a substituted or unsubstituted cyclic group, or a substituted or unsubstituted heterocyclic group, R 6 and R 7 are independently a hydrogen or a substituted or unsubstituted alkyl, and m is an integer from 1 to 10, or two neighboring R groups together with the carbon atoms to which they are attached form a substituted or unsubstituted aryl or a substituted or unsubstituted polyaryl.

9. The method of claim 4 , wherein R 1 -R 4 are independently a hydrogen, an unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted heterocycloalkyl, a C 1 -C 6 haloalkyl, or

 A′ is a single bond or an oxygen, R 8 is a substituted or unsubstituted phenyl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl, and n is an integer from 1 to 8, or two neighboring R groups together with the carbon atoms to which they are attached form a substituted or unsubstituted aryl or a substituted or unsubstituted polyaryl.

10. The method of claim 4 , wherein the quinone has a structure of:

wherein R 1 , R 3 , and R 4 are independently a hydrogen, an unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted heterocycloalkyl, a C 1 -C 6 haloalkyl, or

 A′ is a single bond or an oxygen, R 8 is a substituted or unsubstituted phenyl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl, and n is an integer from 1 to 8, or R 3 and R 4 together with the carbon atoms to which they are attached form a substituted or unsubstituted aryl or a substituted or unsubstituted polyaryl.

11. The method of claim 4 , wherein the quinone has a structure of:

Assignees

• Versitech Ltd
• Laboratory For Synthetic Chemistry And Chemical Biology Ltd

Inventors

• Che Chi Ming
• Wang Tingting
• Wang Haixu

Classifications

• C07C50/12

  Naphthoquinones, i.e. C10H6O2 · CPC title

• C07C50/34

  the quinoid structure being part of a condensed ring system having three rings · CPC title

• C07C50/36

  the quinoid structure being part of a condensed ring system having four or more rings · CPC title

• B01J31/4023

  containing iron group metals, noble metals or copper · CPC title

• C07C50/30

  with polycyclic non-condensed quinoid structure · CPC title