Recent Advances in Transition-Metal-Catalyzed Directing Group Assisted Nitration of Inert C-H Bonds

Abstract

Aromatic nitro compounds are of great importance as chemical raw materials and organic synthesis intermediates. Traditional electrophilic nitration is difficult to achieve regioselective nitrification. In recent years, transition-metal-catalyzed C-H bond activation has developed rapidly. Most functional groups can be introduced into specific sites of aromatics through the chelation of transition metals with directing groups. Directing-group assisted C-H nitration, which is catalyzed by palladium, rhodium, ruthenium and other transition-metal, has made important progress due to its less byproducts, good regioselectivity and environmental protection. According to different transition metal catalysts, the research progress on transition-metal-catalyzed directing-group assisted C-H nitration is summarized, and the limitations of the research field and prospects for future development are presented.

Nitration of Derivatives of Imidazo[1,5‐a]pyridine via C−H Functionalization with Fe(NO3)3 ⋅ 9H2O as a Promoter and a Nitro Source

“…To determine the effects of the loading of Fe(NO 3 ) 3 • 9H 2 O on the yield of the nitration reaction, nitration reactions utilizing different amounts of Fe(NO 3 ) 3 • 9H 2 O were conducted (Table 1, entries [21][22][23]. When the loading of Fe(NO 3 ) 3 • 9H 2 O was as low as 0.2 equivalent, the nitro product was not detected.…”

“…A plethora of nitration strategies have been developed [18–34] . Traditional nitration protocols utilize strong acid systems (concentrated nitric acid with other acids such as H 2 SO 4 , Tf 2 O, Ac 2 O, and HFIP) to produce a nitronium cation (NO 2 + ), which subsequently undergoes an electrophilic substitution reaction with an arene substrate, generating a nitrated product [35–39] .…”

“…Traditional nitration protocols utilize strong acid systems (concentrated nitric acid with other acids such as H 2 SO 4 , Tf 2 O, Ac 2 O, and HFIP) to produce a nitronium cation (NO 2 + ), which subsequently undergoes an electrophilic substitution reaction with an arene substrate, generating a nitrated product [35–39] . Two other main strategies [40–46] include (i) ipso‐nitration of prefunctionalized aromatic compounds, e. g., arylboronic acids, aryl carboxylic acids, aryl halides and pseudohalides, and aryl metal compounds; and (ii) transition‐metal‐catalyzed C(sp 2 )−H nitration of arenes [19,21,47–55] . Recent studies by several groups revealed that the use of ingeniously designed nitrate reagents or N‐nitro‐type reagents, e. g ., 3‐disulfonic acid imidazolium nitrate, [56] guanidine nitrate, [57] 1‐sulfopyridinium nitrate, [58] thiourea nitrate, [59] N‐nitropyrazole, [60] N‐nitrosuccinimide, [61] dinitro‐5,5‐dimethylhydantoin, [62] and N‐nitrosaccharin, [63] etc., as nitro sources, are attractive and powerful methods for nitrating arenes.…”

“…A plethora of nitration strategies have been developed. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Traditional nitration protocols utilize strong acid systems (concentrated nitric acid with other acids such as H 2 SO 4 , Tf 2 O, Ac 2 O, and HFIP) to produce a nitronium cation (NO 2 + ), which subsequently undergoes an electrophilic substitution reaction with an arene substrate, generating a nitrated product. [35][36][37][38][39] Two other main strategies [40][41][42][43][44][45][46] include (i) ipso-nitration of prefunctionalized aromatic compounds, e. g., arylboronic acids, aryl carboxylic acids, aryl halides and pseudohalides, and aryl metal compounds; and (ii) transition-metal-catalyzed C(sp 2 )À H nitration of arenes.…”

“…[35][36][37][38][39] Two other main strategies [40][41][42][43][44][45][46] include (i) ipso-nitration of prefunctionalized aromatic compounds, e. g., arylboronic acids, aryl carboxylic acids, aryl halides and pseudohalides, and aryl metal compounds; and (ii) transition-metal-catalyzed C(sp 2 )À H nitration of arenes. [19,21,[47][48][49][50][51][52][53][54][55] Recent studies by several groups revealed that the use of ingeniously designed nitrate reagents or N-nitro-type reagents, e. g., 3-disulfonic acid imidazolium nitrate, [56] guanidine nitrate, [57] 1-sulfopyridinium nitrate, [58] thiourea nitrate, [59] N-nitropyrazole, [60] N-nitrosuccinimide, [61] dinitro-5,5-dimethylhydantoin, [62] and N-nitrosaccharin, [63] etc., as nitro sources, are attractive and powerful methods for nitrating arenes. Despite the effectiveness of these synthetic strategies, they also suffer from several drawbacks, including functional group intolerance originating from the use of strong acids, the requirement of prefunctionalized arenes for ipso-nitration, the use of prefunctionalized direct groups as chelating moieties for transition metal-catalyzed nitration reactions, and the use of precious metals as catalysts.…”