Nickel-Catalyzed Aminocarbonylation Of Aryl Halides Using Carbamoylsilane As An Amide Source

Amides are very important organic compounds in chemistry,biology and medicine and are widely used in the synthesis of natural products,polymers,cosmetics,electronic products and drugs.Therefore,it is of great significance to study the synthesis of amides.In the past few decades,scientists have proposed a large number of methods for the synthesis of amides.The common method is to use carboxylic acid and its derivatives to react directly with ammonia to form amide,but the steps are cumbersome and the reaction conditions are harsh.Therefore,various other synthesis methods have been developed.Heck reaction is widely used and CO is used as an amide source.There are also many reports of ways to improve the Heck reaction.However,the use of CO as an amide source has drawbacks such as transportation and storage troubles,high temperature,high pressure reaction,and harsh reaction conditions.Therefore,the study of CO-free amide synthesis reactions is a hot topic in chemical synthesis.Cunico's research group reported the aminoacylation of aryl halides with carbamoylsilanes catalyzed by palladium complexes,but palladium catalysts are expensive and pollute the environment.Therefore,the development of a simple,high-efficiency,low-cost,green synthetic amide method is of great significance.In this paper,five kinds of carbamoylsilanes were used as amide sources,and amides were synthesized by the aminoacylation of aryl halides using a non-contaminating nickel complex as a catalyst,and green synthesis was achieved.(1)Using N,N-dimethylcarbamoyltrimethylsilane(I)as the aminoacyl source and tetrakis(triphenylphosphine)nickel(0)as a catalyst in toluene at a temperatureof 75°C,react with bromobenzene(1),chlorobenzene(2),iodobenzene(3),fluoro benzene(4),1-bromo-4-nitrobenzene(5),4-bromochlorobenzene(6),4-bromotoluen e(7),4-bromoanisole(8),2-bromotoluene(9),2,6-dimethylbromobenzene(10),2-br omofluorobenzene(11),2-bromo-5-fluor opyridine(12),2-chloro-5-nitropyridine(13),2-chloro-5-trifluoromethylpyridine(14),2-fluoro-3-nitro-5-trifluoromethylp yridine(15),2-bromonaphthalene(16),2-bromothiophene(17),among them,fluoro benzene(4),2,6-dimethylbromobenzen e(10)and 2-fluoro-3-nitro-5-trifluorometh ylpyridine(15)did not react with each other.The remaining reactions gave the corresponding products,tertiary amides 25-30,32-35,37 and 38.(2)Using N-methyl-N-methoxymethylcarbamoylsilane(II)as the aminoacyl source and tetrakis(triphenylphosphine)nickel(0)as a catalyst in toluene at a temp erature of 75°C,react with bromobenzene(1),1-bromo-4-nitrobenzene(5),4-brom ochlorobenzene(6),4-bromotoluene(7),4-bromoanisole(8),2-bromotoluene(9),2,6-dimethylbromobenzene(10),2-bromoflu orobenzene(11),2-bromo-5-fluoropy ridine(12),2-chloro-5-nitropyridine(13),2-chloro-5-trifluoromethylpyridine(14),2-fluoro-3-nitro-5-trifluoromethylpyridine(15),2-bromonaphthalene(16),2-bromo thiophene(17),2-chloropyridine(18),3-chloropyridine(19),3-bomofuran(20),4-br omobenzonitrile(21),methyl 4-bromobenzoate(22),4'-bromoacetophenone(23),4-bromo-N,N-dimethylaniline(24),among them,2,6-dimethylbromobenzene(10),2-fluoro-3-nitro-5-trifluoromethylpyrid ine(15)and 4'-bromoacetophenone(23)did not react with each other,The corresponding secondary amides 39-44,46-49,51,52,56,57,and 59 were separately synthesized.(3)Using N-propyl-N-methoxymethylcarbamoyltrimethylsilane(III),N-cyclohexyl-N-methoxymethylcarbamoyltrimethylsilane(IV)and N-benzylN-methoxymethylcarbamoyltrimethylsilane(V).These carbamoylsilanes with a large group are used as the aminoacyl source and tetrakis(triphenylphosphine)nick el(0)as a catalyst in toluene at a temperature of 75°C,react with bromobenzene(1),1-bromo-4-nitrobenzene(5),4-bromotoluene(7),4-bromoanisole(8),2-chloro-5-trifluoromethylpyrid-ine(14),2-bromothiophene(17).The corresponding secon dary amides 60-77 were synthesized,wherein the benzyl group contained in theamide 72-77 can be deprotected to form primary amides,and thus is a method for synthesizing primary amides.All the compounds were confirmed by 1H-NMR,C-NMR,IR spectra and elemental analysis.In this study,we have discovered a nickel-catalyzed method for the synthesis of amides by aminoacylation of aryl halides.This method can synthe size primary,secondary,and tertiary amides,and is environmentally friendly,simp le to operate,mild in reaction conditions,and reactive.Moderate yield is an ideal method for the synthesis of amides and will be used in chemical,biological,and pharmaceutical applications.