Heterocyclic coupling catalysts and methods related thereto

Patent metadata

Field	Value
Publication number	US-9700881-B2
Application number	US-201415028205-A
Country	US
Kind code	B2
Filing date	Oct 8, 2014
Priority date	Oct 9, 2013
Publication date	Jul 11, 2017
Grant date	Jul 11, 2017

Abstract

This disclosure relates to synthetic coupling methods using a catalytic molecule comprising two bonded atoms wherein one atom is an amide nitrogen and the second atom is not nitrogen or carbon, such as sulfur, such as a sufur amide nitrogen bond, typically in a heterocycle, such as substituted benzoisothiazolones and derivatives thereof, as a catalyst in the transformation of hydroxy group containing compounds to amides, esters, ketones, and other carbon to heteroatom or carbon to carbon transformations.

First claim

What we claim:

1. A method of catalyzing a coupling reaction comprising mixing
a) a compound comprising a hydroxy group,
b) a trisubstituted phosphite,
c) a nucleophile, and
d) a catalytic heterocycle comprising two bonded heteroatoms wherein one heteroatom is a nitrogen and the second heteroatom is not nitrogen,
under conditions such that a compound is formed comprising the nucleophile in place of the hydroxy group.

2. The method of claim 1 , wherein mixing includes a copper.

3. The method of claim 1 , wherein the trisubstituted phosphite is trialkylphosphite selected from trimethylphosphite, triethylphosphite, tripropylphosphite, triisopropylphosphite, tributyl phosphite, and tert-butylphoshpite.

4. The method of claim 1 , wherein mixing is done under conditions such that an amide, an amine, an ester, an ether, a ketone, or other carbon to carbon bond is formed.

5. The method of claim 1 , wherein the compound comprising a hydroxy group is primary or secondary alcohol or a carboxylic acid.

6. The method of claim 1 , wherein the nucleophile comprising a hydrogen group is a primary or secondary amine, or primary or secondary alcohol, or boronic acid.

7. The method of claim 1 , wherein the catalytic heterocycle is benzoisothiazolone.

8. The method of claim 1 , wherein the catalystic heterocycle linked through a linking group to a silicate, glass, polymer, metal, particle, nanoparticle, magnetic bead, nanostructure, or other solid support.

9. A method of forming an amide or ester comprising mixing
a) a compound comprising a carboxylic acid,
b) a trialkylphosphite,
c) an amine or an alcohol,
d) a catalytic sulfur, amide heterocycle, and
e) copper under conditions such that an amide or an ester is formed.

10. The method of claim 9 , wherein the compound has the following formula:

wherein,
R 1 is selected from alkyl, alkenyl, alkanoyl, cyano, carboxy, alkylamino, dialkylamino, carbocyclyl, aryl, heterocyclyl, amino acid, polypeptide and wherein R 1 is optionally substituted with one or more, the same or different, R 10 or R 15 ;
R 10 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 10 is optionally substituted with one or more, the same or different, R 11 or R 15 ;
R 11 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 11 is optionally substituted with one or more, the same or different, R 12 or R 15 ;
R 12 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 12 is optionally substituted with one or more, the same or different, R 13 or R 15 ;
R 13 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 13 is optionally substituted with one or more, the same or different, R 14 or R 15 ;
R 14 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 14 is optionally substituted with one or more, the same or different, R 15 ; and
R 15 is selected from halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, propyl, tert-butyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl.methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, and heterocyclyl.

11. The method of claim 9 , wherein the amine or the alcohol has the following formula:
H—X—R 2

wherein,
X is O, NH, or NR 3 ;
R 2 is selected from alkyl, alkenyl, alkanoyl, cyano, carboxy, alkylamino, dialkylamino, carbocyclyl, aryl, and heterocyclyl wherein R 2 is optionally substituted with one or more, the same or different, R 20 or R 25 ;
R 20 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 20 is optionally substituted with one or more, the same or different, R 21 or R 25 ;
R 21 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 21 is optionally substituted with one or more, the same or different, R 22 or R 25 ;
R 22 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 22 is optionally substituted with one or more, the same or different, R 23 or R 25 ;
R 23 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 23 is optionally substituted with one or more, the same or different, R 24 or R 25 ;
R 24 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R 24 is optionally substituted with one or more, the same or different, R 25 ;
R 25 is selected from halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, propyl, tert-butyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl.methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, and heterocyclyl;
R 3 is selected from alkyl, alkenyl, alkanoyl, cyano, carbocyclyl, aryl, and heterocyclyl wherein R 3 is optionally substituted with one or more, the same or different, R 30 or R 31 ;
R 30 is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio

Assignees

• Univ Emory

Inventors

• Liebeskind Lanny S
• Lindale Matthew
• Gangireddy Pavan Kumar Reddy

Classifications

• C07C67/08 Primary

  by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds · CPC title

• B01J31/28

  of the platinum group metals, iron group metals or copper · CPC title

• B01J31/0271 Primary

  also containing elements or functional groups covered by B01J31/0201 - B01J31/0231 · CPC title

• C07C49/00

  Ketones; Ketenes; Dimeric ketenes (heterocyclic compounds C07D, e.g. beta-lactones C07D305/12); Ketonic chelates · CPC title

• C07C49/784

  with all keto groups bound to a non-condensed ring · CPC title