Using alkylmetal reagents for directed metalation of azaaromatics

Abstract

Substituted alkylmetal reagents such as (trimethylsilylmethyl)lithium are reacted with pyridinic compounds to produce functionalized pyridinic compounds.

1 . A stabilized reagent mixture comprising a pyridinic compound and a silyl alkylmetal reagent. 
   
   
       2 . The reaction mixture of  claim 1 , wherein the silyl alkylmetal reagent is selected from the group consisting of (trimethylsilylmethyl)lithium, neopentyllithium, bis-(trimethylsilyl)methyllithium, tris-(trimethylsilyl)methyllithium, and isobutyllithium. 
   
   
       3 . The reaction mixture of  claim 1 , wherein the silyl alkylmetal reagent comprises a compound having the formula R 3 W—CH 2 —M, wherein R is selected from the group consisting of alkyl groups, aryl groups, and Si; W is selected from the group consisting of carbon, Si, and Sn; and M is at least one metal selected from the group consisting of lithium, sodium, potassium, cesium, manganese, zinc, and magnesium. 
   
   
       4 . The reaction mixture of  claim 1 , further comprising tetrahydrofuran. 
   
   
       5 . The reaction mixture of  claim 1 , further comprising HCONR 2 , wherein R is an alkyl. 
   
   
       6 . The reaction mixture of  claim 1 , wherein the pyridinic compound is 4-methoxypyridine and the silyl alkylmetal reagent is (trimethylsilylmethyl)lithium. 
   
   
       7 . A stabilized alkylmetal reagent mixture, comprising:
 a substituted alkylmetal reagent; and   an ether.   
   
   
       8 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the substituted alkylmetal reagent is (trimethylsilylmethyl)lithium. 
   
   
       9 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the substituted alkylmetal reagent is selected from the group consisting of (trimethylsilylmethyl)lithium, neopentyllithium, bis-(trimethylsilyl)methyllithium, tris-(trimethylsilyl)methyllithium, and isobutyllithium. 
   
   
       10 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the substituted alkylmetal reagent comprises a compound having the formula R 3 W—CH 2 —M, wherein R is selected from the group consisting of alkyl groups, aryl groups, and Si; W is selected from the group consisting of carbon, Si, and Sn; and M is at least one metal selected from the group consisting of lithium, sodium, potassium, cesium, manganese, zinc, and magnesium. 
   
   
       11 . The stabilized alkylmetal reagent mixture of  claim 10 , wherein M is lithium. 
   
   
       12 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the ether is methyl tert-butyl ether. 
   
   
       13 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the ether is selected from the group consisting of methyl tert-butyl ether, diethyl ether, dimethyl ether, dibutyl ether, cyclopentyl methyl ether, diisopropyl ether, dipropyl ether, dimethoxymethane, dimethoxyethane, diethoxyethane, dioxane, diglyme, triglyme, tetraglyme, and methyl tetrahydrofuran. 
   
   
       14 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the ether is mixed with the substituted alkylmetal reagent in a molar equivalent ratio of about 0.5 to about 3. 
   
   
       15 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the ether is mixed with the substituted alkylmetal reagent in a molar equivalent ratio of about 0.5 to about 1.5. 
   
   
       16 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the ether is mixed with the substituted alkylmetal reagent in a one mole equivalent. 
   
   
       17 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the substituted alkylmetal reagent comprises 25 percent by weight or less of the mixture. 
   
   
       18 . The stabilized alkylmetal reagent mixture of  claim 7 , wherein the substituted alkylmetal reagent comprises 20 percent by weight or less of the mixture.