Silylations of aromatic substrates with base-activated organosilanes

Abstract

The present disclosure describes methods for silylating aromatic organic substrates, and associated chemical systems, said methods comprising or consisting essentially of contacting the aromatic organic substrate with a mixture of (a) at least one organosilane and (b) at least one strong base, under conditions sufficient to silylate the aromatic substrate.

1 . A method of preparing silylated compound comprising a structure of Formula (I) or Formula (II): 
       
         
           
           
               
               
           
         
       
       the method comprising:
 contacting a substrate containing a structure of Formula (IA) or Formula (IIA), respectively 
 
       
         
           
           
               
               
           
         
       
       with (a) a hydrosilane of formula (R 1 ) 3-m Si(H) m+1  and (b) at least one strong base comprising a cesium or potassium alkoxide, a potassium hydride, or potassium bis(trimethylsilyl)amide, under conditions to form the silylated compound, the method resulting in the formation of the silylated compound comprising the structure of Formula (I) or Formula (II);
 wherein 
 m is 0, 1, or 2; 
 R 1  is independently optionally substituted C 1-12  alkyl, C 1-12  heteroalkyl, or an optionally substituted 5- or 6-membered aryl or heteroaryl, and, if substituted, the substituents are independently alkyl, alkenyl, aryl, heteroaryl, hydroxyl, C 1 -C 20  alkoxy, C 5 -C 20  aryloxy, C 2 -C 20  alkoxycarbonyl, C 5 -C 20  aryloxycarbonyl, amino, optionally protected carboxyl, carboxylato, cyano, halo, phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C 1 -C 20  alkylsulfanyl, C 5 -C 20  arylsulfanyl, C 1 -C 20  alkylsulfonyl, C 5 -C 20  arylsulfonyl, C 1 -C 20  alkylsulfinyl, C 5 -C 20  arylsulfinyl, sulfonamido, amido, imino, nitro, nitroso, mercapto, optionally protected formyl, C 1 -C 20  thioester, cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, or boryl; 
 R 2  is H; an optionally substituted linear, branched, cyclic, and/or heteroatom-containing alkyl; or a halo, protected hydroxy, C 1 -C 24  alkoxy, C 2 -C 24  alkenyloxy, C 2 -C 24  alkynyloxy, C 5 -C 24  aryloxy, C 6 -C 24  aralkyloxy, C 6 -C 24  alkaryloxy, optionally protected C 1 -C 24  alkylcarbonyl (—CO-alkyl), optionally protected C 6 -C 24  arylcarbonyl (—CO-aryl)), C 2 -C 24  alkylcarbonyloxy (—O—CO-alkyl), C 6 -C 24  arylcarbonyloxy (—O—CO-aryl)), C 2 -C 24  alkoxycarbonyl ((CO)—O-alkyl), C 6 -C 24  aryloxycarbonyl (—(CO)—O-aryl), halocarbonyl, C 2 -C 24  alkylcarbonato, C 6 -C 24  arylcarbonato, optionally protected carboxy (—COOH), carboxylato (—COO—), carbamoyl (—(CO)—NH 2 ), mono-(C 1 -C 24  alkyl)-substituted carbamoyl (—(CO)NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  alkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 1 -C 24  haloalkyl)-substituted carbamoyl (—(CO)—NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  haloalkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 5 -C 24  aryl)-substituted carbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24  aryl)substituted carbamoyl (—(CO)—N(C 5 -C 24  aryl) 2 ), di-N—(C 1 -C 24  alkyl),N—(C 5 -C 24  aryl)-substituted carbamoyl, thiocarbamoyl (—(CS)—NH 2 ), mono-(C 1 -C 24  alkyl)-substituted thiocarbamoyl (—(CO)—NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  alkyl)-substituted thiocarbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 5 -C 24  aryl)substituted thiocarbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24  aryl)-substituted thiocarbamoyl (—(CO)—N(C 5 -C 24  aryl) 2 ), di-N—(C 1 -C 24  alkyl),N—(C 5 -C 24  aryl)-substituted thiocarbamoyl, carbamido (—NH—(CO)—NH 2 ), cyano(—C—N), cyanato (—O—C═N), thiocyanato (—S—C═N), optionally protected formyl (—(CO)—H), optionally protected thioformyl (—(CS)—H), optionally protected amine, C 1 -C 24  alkylamido (—NH—(CO)-alkyl), C 6 -C 24  arylamido (—NH—(CO)-aryl), imino (—CR═NH where R=hydrogen, C 1 -C 24  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl, C 2 -C 20  alkylimino (—CR═N(alkyl), where R=hydrogen, C 1 -C 24  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl), arylimino (—CR═N(aryl), where R=hydrogen, C 1 -C 20  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl), nitro (—NO 2 ), nitroso (—NO), optionally protected sulfo (—SO 2 OH), sulfonate (SO 2 O—), C 1 -C 24  alkylsulfanyl, C 5 -C 24  arylsulfanyl, C 1 -C 24  alkylsulfinyl (—(SO)-alkyl), C 5 -C 24  arylsulfinyl (—(SO)-aryl), C 1 -C 24  alkylsulfonyl (—SO 2 -alkyl), C 1 -C 24  monoalkylaminosulfonyl-SO 2 —N(H) alkyl), C 1 -C 24  dialkylaminosulfonyl-SO 2 —N(alkyl) 2 , C 5 -C 24  arylsulfonyl (—SO 2 -aryl), boronato (—B(OR) 2  where R is H, alkyl or other hydrocarbyl), phosphono (—P(O)(OH) 2 ), phosphonato (—P(O)(O) 2 ), phosphinato (P(O)(O—)), phospho (—PO 2 ), or phosphine (—PH 2 ); 
 X is NR 3 , O, or S; 
 R 3  is an amine protecting group, an optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkaryl or optionally substituted alk-heteroaryl; 
 
       
         
           
           
               
               
           
         
       
       is a heteroaromatic group containing y additional nitrogens in the ring structure, where y=0 or 1 when X is O or S, or y=0, 1, or 2 when X is NR 3 ; and 
       
         
           
           
               
               
           
         
       
       is an aromatic group containing x nitrogen atoms in the ring structure, wherein x is 0, 1, or 2. 
     
     
         2 . The method of  claim 1 , wherein the silylated compound comprises a structure of Formula (I) and the precursor comprises a structure of Formula (IA): 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 2 , wherein the 
       
         
           
           
               
               
           
         
       
       structure is an optionally substituted furan, pyrrole, thiophene, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, isothiazole, or oxadiazole. 
     
     
         4 . The method of  claim 1 , wherein the silylated compound comprises a structure of Formula (II) and the precursor comprises a structure of Formula (IIA): 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 4 , wherein the 
       
         
           
           
               
               
           
         
       
       structure is an optionally substituted benzofuran, benzopyrrole, benzothiophene, furopyridine, pyrrolopyridine, thienopyridine, furopyrimidine, pyrrolopyrimidine, or thienopyrimidine 
     
     
         6 . The method of  claim 1 , wherein the structures of Formula (IA) or (IIA) are optionally substituted with one or more halo, C 1 -C 24  alkoxy, C 2 -C 24  alkenyloxy, C 2 -C 24  alkynyloxy, C 5 -C 24  aryloxy, C 6 -C 24  aralkyloxy, C 6 -C 24  alkaryloxy, C 1 -C 24  alkylcarbonyl (—CO-alkyl), C 6 -C 24  arylcarbonyl (—CO-aryl)), C 2 -C 24  alkylcarbonyloxy (—O—CO-alkyl), C 6 -C 24  arylcarbonyloxy (—O—CO-aryl)), C 2 -C 24  alkoxycarbonyl ((CO)—O-alkyl), C 6 -C 24  aryloxycarbonyl (—(CO)—O-aryl), halocarbonyl (—CO)—X where X is halo), C 2 -C 24  alkylcarbonato (—O—(CO)—O-alkyl), C 6 -C 24  arylcarbonato (—O—(CO)—O-aryl), carboxy (—COOH), carboxylato (—COO—), carbamoyl (—(CO)—NH 2 ), mono-(C 1 -C 24  alkyl)-substituted carbamoyl (—(CO)NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  alkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 1 -C 24  haloalkyl)-substituted carbamoyl (—(CO)—NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  haloalkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 5 -C 24  aryl)-substituted carbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24  aryl)substituted carbamoyl (—(CO)—N(C 5 -C 24  aryl) 2 ), di-N—(C 1 -C 24  alkyl),N—(C 5 -C 24  aryl)-substituted carbamoyl, thiocarbamoyl (—(CS)—NH 2 ), mono-(C 1 -C 24  alkyl)-substituted thiocarbamoyl (—(CO)—NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  alkyl)-substituted thiocarbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 5 -C 24  aryl)substituted thiocarbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24  aryl)-substituted thiocarbamoyl (—(CO)—N(C 5 -C 24  aryl) 2 ), di-N—(C 1 -C 24  alkyl),N—(C 5 -C 24  aryl)-substituted thiocarbamoyl, carbamido (—NH—(CO)—NH 2 ), cyano(—C—N), cyanato (—O—C═N), thiocyanato (—S—C═N), formyl (—(CO)—H), thioformyl (—(CS)—H), amino (—NH 2 ), mono-(C 1 -C 24  alkyl)-substituted amino, di-(C 1 -C 24  alkyl)-substituted amino, mono-(C 5 -C 24  aryl)substituted amino, di-(C 5 -C 24  aryl)-substituted amino, C 1 -C 24  alkylamido (—NH—(CO)-alkyl), C 6 -C 24  arylamido (—NH—(CO)-aryl), imino (—CR═NH where R=hydrogen C 1 -C 24  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl), C 2 -C 20  alkylimino (—CR═N(alkyl), where R=hydrogen, C 1 -C 24  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl), arylimino (—CR═N(aryl), where R=hydrogen, C 1 -C 20  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl), nitro (—NO 2 ), nitroso (—NO), sulfo (—SO 2 OH), sulfonate (SO 2 O—), C 1 -C 24  alkylsulfanyl (—S-alkyl; also termed “alkylthio”), C 5 -C 24  arylsulfanyl (—S-aryl; also termed “arylthio”), C 1 -C 24  alkylsulfinyl (—(SO)-alkyl), C 5 -C 24  arylsulfinyl (—(SO)-aryl), C 1 -C 24  alkylsulfonyl (—SO 2 -alkyl), C 1 -C 24  monoalkylaminosulfonyl-SO 2 —N(H) alkyl), C 1 -C 24  dialkylaminosulfonyl-SO 2 —N(alkyl) 2 , C 5 -C 24  arylsulfonyl (—SO 2 -aryl), boryl (—BH 2 ), borono (—B(OH) 2 ), boronato (—B(OR) 2  where R is alkyl or other hydrocarbyl), phosphono (—P(O)(OH) 2 ), phosphonato (—P(O)(O) 2 ), phosphinato (P(O)(O—)), phospho (—PO 2 ), phosphine (—PH 2 ), C 1 -C 24  alkyl, C 2 -C 24  alkenyl, C 2 -C 24  alkynyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, or C 6 -C 24  aralkyl. 
     
     
         7 . The method of  claim 1 , wherein the at least one strong base comprises a potassium alkoxide or cesium alkoxide. 
     
     
         8 . The method of  claim 7 , wherein the potassium alkoxide or cesium alkoxide comprises a C 1-12  linear or branched alkyl moiety or a C 5-10  aryl or heteroaryl moiety. 
     
     
         9 . The method of  claim 1 , wherein the at least one strong base comprises potassium methoxide, potassium ethoxide, a potassium propoxide or a potassium butoxide. 
     
     
         10 . The method of  claim 1 , wherein the at least one strong base comprises potassium tert-butoxide. 
     
     
         11 . The method of  claim 1 , wherein the at least one strong base comprises potassium hydride. 
     
     
         12 . The method of  claim 1 , wherein the at least one strong base comprises potassium bis(trimethylsilyl)amide. 
     
     
         13 . The method of  claim 1 , wherein m=0. 
     
     
         14 . The method of  claim 1 , wherein m=1. 
     
     
         15 . The method of  claim 1 , wherein m=2. 
     
     
         16 . The method of  claim 1  where R 1  is independently optionally substituted cyclic alkyl or branched alkyl or cyclic or branched heteroalkyl. 
     
     
         17 . The method of  claim 1 , wherein R 1  is independently optionally substituted C 1-12  alkyl, optionally substituted heteroaryl or optionally substituted C 2-12  heterocycloalkyl. 
     
     
         18 . The method of  claim 1 , wherein R 1  is independently tert-butyl, —C(CH 3 ) 2 (CN), pyridine, or an alkyl substituted heterocycloalkyl. 
     
     
         19 . The method of  claim 14 , wherein R 1  is independently optionally substituted cyclic alkyl or branched alkyl or cyclic or branched heteroalkyl. 
     
     
         20 . The method of  claim 14 , wherein R 1  is independently optionally substituted C 1-12  alkyl, optionally substituted heteroaryl or optionally substituted C 2-12  heterocycloalkyl. 
     
     
         21 . The method of  claim 14 , wherein R 1  is independently tert-butyl, —C(CH 3 ) 2 (CN), pyridine, or an alkyl substituted heterocycloalkyl. 
     
     
         22 . The method of  claim 1 , wherein x and y=0 or 1. 
     
     
         23 . The method of  claim 1 , wherein X is O or S. 
     
     
         24 . The method of  claim 1 , wherein X is NR 3 . 
     
     
         25 . The method of  claim 1 , wherein R 2  is H. 
     
     
         26 . The method of  claim 1 , wherein R 2  is an optionally substituted linear, branched, cyclic, and/or heteroatom-containing alkyl. 
     
     
         27 . The method of  claim 1 , wherein:
 (a) the hydrosilane and the at least one strong base are present together at a molar ratio, with respect to one another, in a range of from 20:1 to 1:1; and/or   (b) the at least one strong base and organic substrate are present together at a molar ratio, with respect to one another, in a range of from 0.01:1 to 0.9:1.   
     
     
         28 . The method of  claim 1 , wherein the contacting is done in the absence of added transition-metal species. 
     
     
         29 . A composition useful in the method of  claim 1 , the composition comprising:
 (a) an organic substrate comprising a structure:   
       
         
           
           
               
               
           
         
         (b) at least one hydrosilane of formula (R 1 ) 3-m Si(H) m+1 ; and 
         (c) at least one strong base comprising an alkali metal alkoxide, an alkali metal hydride, an alkaline earth metal hydride, or potassium bis(trimethylsilyl)amide; and optionally 
         (d) a silylated derivative of the organic substrate comprising a structure of Formula (I) or Formula (II): 
       
       
         
           
           
               
               
           
         
         wherein 
         m is 0, 1, or 2; 
         R 1  is independently optionally substituted C 1-12  alkyl, C 1-12  heteroalkyl, or an optionally substituted 5- or 6-membered aryl or heteroaryl, and, if substituted, the substituents are independently alkyl, alkenyl, aryl, heteroaryl, hydroxyl, C 1 -C 20  alkoxy, C 5 -C 20  aryloxy, C 2 -C 20  alkoxycarbonyl, C 5 -C 20  aryloxycarbonyl, amino, optionally protected carboxyl, carboxylato, cyano, halo, phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C 1 -C 20  alkylsulfanyl, C 5 -C 20  arylsulfanyl, C 1 -C 20  alkylsulfonyl, C 5 -C 20  arylsulfonyl, C 1 -C 20  alkylsulfinyl, C 5 -C 20  arylsulfinyl, sulfonamido, amido, imino, nitro, nitroso, mercapto, optionally protected formyl, C 1 -C 20  thioester, cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, or boryl; 
         R 2  is H; an optionally substituted linear, branched, cyclic, and/or heteroatom-containing alkyl; or a halo, protected hydroxy, C 1 -C 24  alkoxy, C 2 -C 24  alkenyloxy, C 2 -C 24  alkynyloxy, C 5 -C 24  aryloxy, C 6 -C 24  aralkyloxy, C 6 -C 24  alkaryloxy, optionally protected C 1 -C 24  alkylcarbonyl (—CO-alkyl), optionally protected C 6 -C 24  arylcarbonyl (—CO-aryl)), C 2 -C 24  alkylcarbonyloxy (—O—CO-alkyl), C 6 -C 24  arylcarbonyloxy (—O—CO-aryl)), C 2 -C 24  alkoxycarbonyl ((CO)—O-alkyl), C 6 -C 24  aryloxycarbonyl (—(CO)—O-aryl), halocarbonyl, C 2 -C 24  alkylcarbonato, C 6 -C 24  arylcarbonato, optionally protected carboxy (—COOH), carboxylato (—COO—), carbamoyl (—(CO)—NH 2 ), mono-(C 1 -C 24  alkyl)-substituted carbamoyl (—(CO)NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  alkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 1 -C 24  haloalkyl)-substituted carbamoyl (—(CO)—NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  haloalkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 5 -C 24  aryl)-substituted carbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24  aryl)substituted carbamoyl (—(CO)—N(C 5 -C 24  aryl) 2 ), di-N—(C 1 -C 24  alkyl),N—(C 5 -C 24  aryl)-substituted carbamoyl, thiocarbamoyl (—(CS)—NH 2 ), mono-(C 1 -C 24  alkyl)-substituted thiocarbamoyl (—(CO)—NH(C 1 -C 24  alkyl)), di-(C 1 -C 24  alkyl)-substituted thiocarbamoyl (—(CO)—N(C 1 -C 24  alkyl) 2 ), mono-(C 5 -C 24  aryl)substituted thiocarbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24  aryl)-substituted thiocarbamoyl (—(CO)—N(C 5 -C 24  aryl) 2 ), di-N—(C 1 -C 24  alkyl),N—(C 5 -C 24  aryl)-substituted thiocarbamoyl, carbamido (—NH—(CO)—NH 2 ), cyano(—C—N), cyanato (—O—C═N), thiocyanato (—S—C═N), optionally protected formyl (—(CO)—H), optionally protected thioformyl (—(CS)—H), optionally protected amine, C 1 -C 24  alkylamido (—NH—(CO)-alkyl), C 6 -C 24  arylamido (—NH—(CO)-aryl), imino (—CR═NH where R=hydrogen, C 1 -C 24  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl, C 2 -C 20  alkylimino (—CR═N(alkyl), where R=hydrogen, C 1 -C 24  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl), arylimino (—CR═N(aryl), where R=hydrogen, C 1 -C 20  alkyl, C 5 -C 24  aryl, C 6 -C 24  alkaryl, C 6 -C 24  aralkyl), nitro (—NO 2 ), nitroso (—NO), optionally protected sulfo (—SO 2 OH), sulfonate (SO 2 O—), C 1 -C 24  alkylsulfanyl, C 5 -C 24  arylsulfanyl, C 1 -C 24  alkylsulfinyl (—(SO)-alkyl), C 5 -C 24  arylsulfinyl (—(SO)-aryl), C 1 -C 24  alkylsulfonyl (—SO 2 -alkyl), C 1 -C 24  monoalkylaminosulfonyl-SO 2 —N(H) alkyl), C 1 -C 24  dialkylaminosulfonyl-SO 2 —N(alkyl) 2 , C 5 -C 24  arylsulfonyl (—SO 2 -aryl), boronato (—B(OR) 2  where R is H, alkyl or other hydrocarbyl), phosphono (—P(O)(OH) 2 ), phosphonato (—P(O)(O) 2 ), phosphinato (P(O)(O—)), phospho (—PO 2 ), or phosphine (—PH 2 ); 
         X is NR 3 , O, or S; 
         R 3  is an amine protecting group, an optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkaryl or optionally substituted alk-heteroaryl; 
       
       
         
           
           
               
               
           
         
       
       is a heteroaromatic group containing y additional nitrogens in the ring structure, where y=0 or 1 when X is O or S, or y=0, 1, or 2 when X is NR 3 ; and 
       
         
           
           
               
               
           
         
       
       is an aromatic group containing x nitrogen atoms in the ring structure, wherein x is 0, 1, or 2.