Silylation of aromatic heterocycles by disilanes using potassium alkoxide catalysts
The present invention describes chemical systems and methods for silylating heteroaromatic organic substrates using at least alkoxide base, preferably a potassium alkoxide base and at least one organodisilane and (b) at least one alkoxide base. Both methods and compositions for affecting these transformations are disclosed.
1. A method comprising contacting an organic substrate having a heteroaromatic moiety with a mixture comprising (a) at least one organodisilane and (b) at least one potassium alkoxide base, in the presence of an organic solvent having an oxygen donor group, under conditions sufficient to silylate the organic substrate, the method resulting in a heteroaromatic silylated product, wherein the at least one organodisilane comprises an organodisilane of Formula (I):
(R) 3 Si—Si(R) 3 (I)
wherein:
each R is independently H, C 1-12 alkyl, C 1-12 heteroalkyl, C 2-12 alkenyl, C 2-12 heteroalkenyl, C 2-12 alkynyl, heteroalkynyl, C 6-20 aryl, C 3-20 heteroaryl, C 7-30 alkaryl, C 6-30 heteroalkaryl, C 7-30 aralkyl, C 5-30 heteroaralkyl, —O—C 1-12 alkyl, —O—C 1-12 heteroalkyl, —O—C 6-20 aryl, —O—C 3-20 heteroaryl, —O—C 7-30 alkaryl, —O—C 5-30 heteroalkaryl, —O—C 7-30 aralkyl, or —O—C 5-30 heteroaralkyl, and wherein
each C 1-12 alkyl, C 1-12 heteroalkyl, C 2-12 alkenyl, C 2-12 heteroalkenyl, C 2-12 alkynyl, heteroalkynyl, C 6-20 aryl, C 3-20 heteroaryl, C 7-30 alkaryl, C 6-30 heteroalkaryl, C 7-30 aralkyl, C 5-30 heteroaralkyl, —O—C 1-12 alkyl, —O—C 1-12 heteroalkyl, —O—C 6-20 aryl, —O—C 3-20 heteroaryl, —O—C 7-30 alkaryl, —O—C 5-30 heteroalkaryl, —O—C 7-30 aralkyl, or —O—C 5-30 heteroaralkyl is optionally substituted with phosphonato, phosphoryl, phosphino, sulfonato, C 1 -C 20 alkylsulfanyl, C 6-20 arylsulfanyl , C 1 -C 20 alkylsulfonyl, C 6-20 arylsulfonyl, C 1 -C 20 alkylsulfinyl, C 6-20 arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C 1 -C 20 alkoxy, C 6-20 aryloxy, C 2 -C 20 alkoxycarbonyl, C 6-20 aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C 1 -C 20 thioester, cyano, cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or where the substituents optionally provide a tether to an insoluble or sparingly soluble support media comprising alumina, silica, or carbon.
2. The method of claim 1 , wherein the mixture and organic substrate are free of added transition-metal compounds or catalysts.
3. The method of claim 1 , wherein at least one R is hydrogen, and each remaining R is independently C 1-6 alkyl.
4. The method of claim 1 , wherein the at least one potassium alkoxide base comprises a C 1-12 alkyl moiety.
5. The method of claim 1 , wherein the at least one potassium alkoxide base comprises a C 6-10 aryl or C 5-10 aryl heteroaryl moiety.
6. The method of claim 1 , wherein the at least one potassium alkoxide base comprises potassium methoxide, potassium ethoxide, potassium propoxide, or potassium butoxide.
7. The method of claim 1 , wherein the at least one potassium alkoxide base comprises potassium tert-butoxide.
8. The method of claim 1 , wherein the organic substrate comprises an optionally substituted furan, pyrrole, thiophene, pyrazole, or imidazole moiety.
9. The method of claim 1 , wherein the organic substrate comprises an optionally substituted benzofuran, benzothiophene, indole, azaindole, dibenzofuran, xanthene, dibenzopyrrole, pyridine, a pyrrolopyridine, a pyrrolopyrimidine, or a dibenzothiophene.
10. The method of claim 1 , wherein the organic substrate comprises an optionally substituted furan, pyrrole, thiophene, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, isothiazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazone, benzofuran, benzothiophene, isobenzofuran, isobenzothiophene, indole, isoindole, indolizine, indazole, azaindole, benzisoxazole, benzoxazole, quinoline, isoquinoline, cinnoline, quinazoline, naphthyridine, 2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole, 2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, or dibenzothiophene.
11. The method of claim 1 , wherein the organic substrate comprises a heteroaryl moiety of structure:
where
X is N—R″, O, or S;
p is 0, 1, or 2;
R′ is a halo, hydroxyl, sulfhydryl, alkoxy, C 1 -C 24 alkyl, C 2 -C 24 alkenyl, aryloxy, aralkyloxy, alkaryloxy, acyl, acyloxy, alkoxycarbonyl, aryloxycarbonyl, halocarbonyl, alkylcarbonato, arylcarbonato, carboxylato (COO—), dialkyl-substituted carbamoyl, di-haloalkyl-substituted carbamoyl, di aryl-substituted carbamoyl, di-alkyl-substituted thiocarbamoyl, di-aryl-substituted thiocarbamoyl, di-N-alkyl, N-aryl-substituted thiocarbamoyl, cyano, cyanato, thiocyanato, di-alkyl-substituted amino, di-aryl-substituted amino, arylimino, nitro, nitroso, alkylsulfanyl, arylsulfanyl, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, or boronato; or (R′) p comprises an optionally substituted fused methylene linked diether, ethylene linked diether, or propylene linked diether, aryl or heteroaryl moiety; and
R″ is an amine protecting group or an optionally substituted alkyl, aryl, heteroaryl, alkaryl or alk-heteroaryl.
12. The method of claim 1 , wherein the organic substrate comprises a heteroaryl moiety of structure:
where
X is N—R″, O, or S;
p is 0, 1, or 2;
R′ is a halo, hydroxyl, sulfhydryl, alkoxy, C 1 -C 24 alkyl, C 2 -C 24 alkenyl, aryloxy, aralkyloxy, alkaryloxy, acyl, acyloxy, alkoxycarbonyl, aryloxycarbonyl, halocarbonyl, alkylcarbonato, arylcarbonato, carboxylato (COO—), dialkyl-substituted carbamoyl, di-haloalkyl-substituted carbamoyl, di-aryl-substituted carbamoyl, di-alkyl-substituted thiocarbamoyl, di-aryl-substituted thiocarbamoyl, di-N-alkyl, N-aryl-substituted thiocarbamoyl, cyano, cyanato, thiocyanato, di-alkyl-substituted amino, di-aryl-substituted amino, arylimino, nitro, nitroso, alkylsulfanyl, arylsulfanyl, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, or boronato; or (R′) p comprises an optionally substituted fused methylene linked diether, ethylene linked diether, or propylene linked diether, aryl or heteroaryl moiety; and
R″ is an amine protecting group or an optionally substituted alkyl, aryl, heteroaryl, alkaryl or alk-heteroaryl.
13. The method of claim 1 , wherein the organic substrate having a heteroaromatic moiety is polymeric.
14. The method of claim 1 , wherein the heteroaromatic silylated product is further reacted under conditions sufficient to:
(a) couple the heteroaromatic silylated product with a second aromatic compound to form a biaromatic product, the method resulting in the formation of the biaromatic product;
(b) convert the heteroaromatic silylated product to a hydroxylated, alkoxylated, aryloxylated, alkyl carboxylated, or aryl carboxylated product, the method resulting in the formation of the hydroxylated, alkoxylated, aryloxylated, alkyl carboxylated, or aryl carboxylated product, wherein the hydroxylated product is an optionally hydroxy-protected product;
(c) convert the heteroaromatic silylated product to a heteroaromatic alpha-olefin product, the method resulting in the formation of the heteroaromatic alpha-olefin product;
(d) convert the heteroaromatic silylated product to a heteroaromatic chloro, bromo, fluoro, iodo, nitrate, or nitrite the method resulting in the formation of the heteroaromatic chloro, bromo, fluoro, iodo, nitrate, or nitrite product; or
(e) convert the heteroaromatic silylated product to a heteroaromatic boronic halide or boronic ester.
15. The method of claim 1 , where the organic substrate comprises a thiophene moiety, wherein the heteroaromatic silylated product is a silylated thiophene product and the silylated thiophene product is further reacted under conditions sufficient to convert the heteroaromatic silylated product to an alternating thiophene-perfluoroarene copolymer.
16. The method of claim 1 , wherein the organic solvent comprises a non-tertiary ether or an alkylphosphoramide solvent.
17. The method of claim 1 , wherein the organic solvent comprises hexamethylphosphoramide (HMPA), tetrahydrofuran (THF), 2-methyl-THF, or a dioxane.
18. A composition comprising:
(a) an organic substrate comprising a heteroaromatic moiety and a silylated derivative thereof, said silylated derivative having a C—Si bond in a position corresponding to a position in the heteroaromatic moiety of the organic substrate having a C—H bond;
(b) at least one organodisilane; and
(c) at least one potassium alkoxide base;
wherein the at least one organodisilane comprises an organodisilane of Formula (I):
(R) 3 Si—Si(R) 3 (I)
wherein:
each R is independently H, C 1-12 alkyl, C 1-12 heteroalkyl, C 2-12 alkenyl, C 2-12 heteroalkenyl, C 2-12 alkynyl, heteroalkynyl, C 6-20 aryl, C 3-20 heteroaryl, C 7-30 alkaryl, C 6-30 heteroalkaryl, C 7-30 aralkyl, C 5-30 heteroaralkyl, —O—C 1-12 alkyl, —O—C 1-12 heteroalkyl, —O—C 6-20 aryl, —O—C 3-20 heteroaryl, —O—C 7-30 alkaryl, —O—C 5-30 heteroalkaryl, —O—C 7-30 aralkyl, or —O—C 5-30 heteroaralkyl, and wherein
each C 1-12 alkyl, C 1-12 heteroalkyl, C 2-12 alkenyl, C 2-12 heteroalkenyl, C 2-12 alkynyl, heteroalkynyl, C 6-20 aryl, C 3-20 heteroaryl, C 7-30 alkaryl, C 6-30 heteroalkaryl, C 7-30 aralkyl, C 5-30 heteroaralkyl, —O—C 1-12 alkyl, —O—C 1-12 heteroalkyl, —O—C 6-20 aryl, —O—C 3-20 heteroaryl, —O—C 7-30 alkaryl, —O—C 5-30 heteroalkaryl, —O—C 7-30 aralkyl, or —O—C 5-30 heteroaralkyl is optionally substituted with phosphonato, phosphoryl, phosphino, sulfonato, C 1 -C 20 alkylsulfanyl, C 6-20 arylsulfanyl , C 1 -C 20 alkylsulfonyl, C 6-20 arylsulfonyl, C 1 -C 20 alkylsulfinyl, C 6-20 arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C 1 -C 20 alkoxy, C 6-20 aryloxy, C 2 -C 20 alkoxycarbonyl, C 6-20 aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C 1 -C 20 thioester, cyano, cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or where the substituents optionally provide a tether to an insoluble or sparingly soluble support media comprising alumina, silica, or carbon.
19. The composition of claim 18 , further comprising an organic solvent having an oxygen donor group.
20. The composition of claim 19 , wherein the organic solvent comprises a non-tertiary ether or an alkylphosphoramide solvent.
21. The composition of claim 19 , wherein the organic solvent comprises hexamethylphosphoramide (HMPA), tetrahydrofuran (THF), 2-methyl-THF, or a dioxane.
22. The composition of claim 18 , that is free of added transition-metal compounds or catalysts.
23. The method of claim 8 , wherein the optional substituent is a C 1 -C 24 alkyl or C 2 -C 24 alkenyl.
24. The method of claim 9 , wherein the optional substituent is a C 1 -C 24 alkyl or C 2 -C 24 alkenyl.
25. The method of claim 10 , wherein the optional substituent is a C 1 -C 24 alkyl or C 2 -C 24 alkenyl.