Heterocyclic Coupling Catalysts and Methods Related Thereto

Patent metadata

Field	Value
Publication number	US-2016243534-A1
Application number	US-201415028205-A
Country	US
Kind code	A1
Filing date	Oct 8, 2014
Priority date	Oct 9, 2013
Publication date	Aug 25, 2016
Grant date	—

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, carb

Assignees

• Univ Emory

Inventors

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

Classifications

• C07C231/02

  from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines · CPC title

• C07D209/20

  substituted additionally by nitrogen atoms, e.g. tryptophane · CPC title

• C07C67/08 Primary

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

• C07C269/06

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

• B01J31/0271 Primary

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