Surfactant-Enabled Transition Metal-Catalyzed Chemistry

Abstract

In one embodiment, the present application discloses mixtures comprising (a) water in an amount of at least 1% wt/wt of the mixture; (b) a transition metal catalyst; and (c) one or more solubilizing agents; and methods for using such mixtures for performing transition metal mediated bond formation reactions.

We claim: 
     
         1 .- 14 . (canceled) 
     
     
         15 . A method for performing a transition metal mediated bond formation, the method comprising:
 contacting a coupling substrate with a mixture comprising:   (a) water in an amount of at least 1% wt/wt of the mixture;   (b) a transition metal catalyst; and   (c) one or more solubilizing agents selected from the group consisting of solubilizing agents having a hydrophilic-lipophilic balance (HLB) of 8-18, HLB of 7-9, HLB of 8-12 or HLB of 13-15, or a solubilizing agent having the formula
   Y 1 -L 1 -Z 
   wherein Z is a natural or synthetic alpha-tocopherol, or a ubiquinol moiety containing a covalently bound catalyst,   and Y 1 -L 1 - has the formula:   
       
         
           
           
               
               
           
         
         wherein n is an integer selected from 1-14, 
         k is an integer selected from 1-250, and 
         Y 7  is selected from H and methyl, or mixtures of solubilizing agents; 
         with the proviso that if Y 7  is H and n is 8, k is not an integer from 13-15; and 
         if Y 7  is H and n is 2, k is not an integer from 21-24; 
         under conditions appropriate to form a bond between a first atom of the coupling substrate and a second atom of a member selected from (i) the coupling substrate and (ii) a coupling partner. 
       
     
     
         16 . The method of  claim 15 , wherein the transition metal mediated bond formation is performed in an aqueous solvent. 
     
     
         17 . The method of  claim 15 , wherein the transition metal catalyst is selected from an organo-palladium or -nickel reagent, organo-copper or -gold reagent, organo-rhodium or -iridium complex, or an organo-ruthenium, -iron, or -osmium reagent, wherein the catalyst is capable of promoting cross-coupling reactions, or other reactions characteristic of catalysis by these metals, that form a carbon-carbon, carbon-heteroatom or carbon-hydrogen bond. 
     
     
         18 . The method of  claim 15 , wherein Y 7  is methyl. 
     
     
         19 . The method of  claim 15 , wherein the solubilizing agent is selected from the group consisting of Poloxamer 188, Polysorbate 80, Polysorbate 20, Vit E-TPGS, Solutol HS 15, PEG-40 Hydrogenated castor oil (Cremophor RH40), PEG-35 Castor oil (Cremophor EL), PEG-8-glyceryl capylate/caprate (Labrasol), PEG-32-glyceryl laurate (Gelucire 44/14), PEG-32-glyceryl palmitostearate (Gelucire 50/13); Polysorbate 85, polyglyceryl-6-dioleate (Caprol MPGO), mixtures of high and low HLB emulsifiers; sorbitan monooleate (Span 80), Capmul MCM, Maisine 35-1, glyceryl monooleate, glyceryl monolinoleate, PEG-6-glyceryl oleate (Labrafil M 1944 CS), PEG-6-glyceryl linoleate (Labrafil M 2125 CS), oleic acid, linoleic acid, propylene glycol monocaprylate (e.g. Capmul PG-8 or Capryol 90), propylene glycol monolaurate (e.g., Capmul PG-12 or Lauroglycol 90), polyglyceryl-3 dioleate (Plurol Oleique CC497), polyglyceryl-3 diisostearate (Plurol Diisostearique), lecithin with and without bile salts, and a solubilizing agent having the formula Y 1 -L 1 -Z; or combinations thereof. 
     
     
         20 . The method of  claim 15 , wherein the transition metal catalyst comprises less than 5 mole %, less than 3 mole % or less than 2 mole % of the mixture. 
     
     
         21 . The method of  claim 15 , wherein water is the sole solvent. 
     
     
         22 . The method of  claim 15 , wherein the coupling substrate is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; and wherein the coupling partner is selected from H, substituted or unsubstituted amine, substituted or unsubstituted silane, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. 
     
     
         23 . The method of  claim 15 , wherein the coupling substrate is a substituted or unsubstituted alkene, a substituted or unsubstituted alkyne, a substituted or unsubstituted enyne, a substituted or unsubstituted enone or enoate or a substituted or unsubstituted ynone or ynoate. 
     
     
         24 . The method of  claim 15 , wherein the coupling substrate is selected from a substituted or unsubstituted vinyl halide, substituted or unsubstituted vinyl pseudohalide, substituted or unsubstituted allylic alcohol, substituted or unsubstituted allylic ether, substituted or unsubstituted aryl or heteroaryl halide and substituted or unsubstituted aryl or heteroaryl pseudohalide. 
     
     
         25 . The method of  claim 15 , wherein the coupling partner is selected from a mono-substituted, disubstituted, trisubstituted, or tetrasubstituted alkene, mono-substituted or disubstituted alkyne, substituted or unsubstituted aryl or heteroaryl halide and substituted or unsubstituted aryl or heteroaryl pseudohalide. 
     
     
         26 . The method of  claim 15 , wherein the mixture provides a medium for transition metal-catalyzed cross-coupling reaction comprising olefin cross-metathesis, ring closing metathesis, Sonogashira coupling, Heck coupling, direct amination of free allylic alcohols, aminations of allylic ethers, C—H activation reactions (e.g., Fujiwara-Moritani couplings, arylations and heteroarylations of aromatic and heteroaromatic rings, etc.), Suzuki-Miyaura coupling, Buchwald-Hartwig amination, Negishi couplings, benzylic couplings (halides, pseudohalides, etc.) with aryl halides or pseudohalides, silylations of allylic ethers, and all types of aryl-aryl (e.g., combinations of aromatic and heteroaromatic) cross-couplings (biaryl formation).