A Cross-Coupling Approach to Amide Bond Formation from Esters

Abstract

A palladium-catalyzed cross-coupling between aryl esters and anilines is reported, enabling access to diverse amides. The reaction takes place via activation of the C–O bond by oxidative addition with a Pd–NHC complex, which enables the use of relatively non-nucleophilic anilines that otherwise require stoichiometric activation with strong bases in order to react. High yields of aromatic, aliphatic, and heterocyclic products are obtained. A range of activated esters are evaluated in the presence and absence of catalyst, demonstrating that the catalytic methodology substantially increases the types of electrophiles that can be utilized for amide bond formation in the absence of harsh bases.

Facile amidation of esters with aromatic amines promoted by lanthanide tris (amide) complexes

“…Moreover, this approach is superior to conventional methods with respect to that the sole byproduct is an alcohol. Some catalytic systems have been developed to promote this transformation, including inorganic bases (such as LiOH, K 3 PO 4 , NaOMe), organic catalysts (such as BEMP, 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), DBU, 1,2,4‐triazole, NHCs,), enzyme, and metal complexes (such as Pd (IPr)(allyl)Cl, Ni (cod) 2 , La (OTf) 3 , Ru‐PNN, AlMe 3 , Zr complexes, Ln 2 Na 8 (OCH 2 CF 3 ) 14 (THF) 6, CaI 2 ). Nevertheless, further improvement is still required to expand the substrate scope and to realize the catalytic reaction under mild conditions.…”

“…Nevertheless, further improvement is still required to expand the substrate scope and to realize the catalytic reaction under mild conditions. For example, in the reported successful cases the amines used are mostly restricted to aliphatic amines, whilst less nucleophilic aromatic amines are poorly exploited . Furthermore, the amidation of esters with aromatic amines is usually performed at a high temperature and needs a long reaction time .…”

“…For example, in the reported successful cases the amines used are mostly restricted to aliphatic amines, whilst less nucleophilic aromatic amines are poorly exploited . Furthermore, the amidation of esters with aromatic amines is usually performed at a high temperature and needs a long reaction time . Therefore, the development of catalysts capable of promoting the amidation of esters with aromatic amines under mild conditions is of great importance.…”

Heterobimetallic Lanthanide–Sodium Alkoxides Catalyze the Amidation of Esters

“…Moreover, the only byproducts of the reactiona re alcohols, an outcome that is also superior to conventional methods in terms of green chemistry.S ystems have been developed to catalyzet his transformation,i nvolving heterogeneous catalysts, [4] inorganic salts or bases, [5][6][7][8][9][10][11] organicc atalysts [12][13][14][15][16][17] ,e nzymes, [18] and metal complexes. [19][20][21][22][23][24][25] In general,l arge loadings of catalysts (nearlys toichiometric)a re required, and substrates are mainly limited to reactive aliphatic amines such as benzylamine and hexylamine. One report by Morimoto and Ohshima et al shows that lanthanum(III) trifluoromethanesulfonate, La(OTf) 3 ,a t2 -5 mol %l oading is one of the most efficient catalysts for this type of amidation reaction.…”

“…One report by Morimoto and Ohshima et al shows that lanthanum(III) trifluoromethanesulfonate, La(OTf) 3 ,a t2 -5 mol %l oading is one of the most efficient catalysts for this type of amidation reaction. [22] Recently,l ate transition metal complexes ([Ni(cod) 2 ]/1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene [24] and Pd-1,3-bis(2,6-diisopropylphenyl)i-midazol-2-ylidene complex [25] )h ave been reported to promote amidation of aniline derivatives. The development of simple yet efficient catalysts that promote the direct amidationo f esters under mild conditions with low catalystl oadings is highly desirable.…”