Synthesis of 2-Aminobutene-1,4-Diones by Gold-Catalysed Three-Component Coupling Reactions

Abstract

Compounds which have the 2-aminobutene-1,4-dione skeleton can be found in many drugs, bio-active compounds and industrial products. [1][2][3][4] Additionally, these 2-aminobutene-1,4-diones can also serve as useful tools for constructing heterocyclic compounds in organic synthesis containing, for example, pyrrole, hydrazine, furan and cyclopentenone moieties. [5][6][7][8] As a consequence, various methods for their preparation have been reported previously, for example, conjugate addition of diaroylacetylenes or sulfur ylides to aryl azides, 9,10 using α,β-unsaturated γ-dicarbonyl or acetophenones with amines, 11,12 reaction of pyridinium bromides and primary aromatic amines with phenylglyoxal or ethyl glyoxalate 13 and other ways. 14,15 Recently, Wu and co-workers developed an efficient Cu-catalysed tandem reaction to synthesise 2-aminobutene-1,4-diones in good yields, but a long reaction time is needed. 16 Here, we develop a simple and convenient method by a multi-component reaction process to access 2-aminobutene-1,4-diones rapidly.Gold catalysis offers new ways for the efficient construction of complex molecules and has attracted much attention because of the catalyst's soft and carbophilic Lewis acidity in recent years. [17][18][19][20] Furthermore, Au-catalysed reactions generally proceed under very mild conditions with small amounts of catalyst. In 2013 we reported a new gold-catalysed three-component coupling (TCC) reaction of phenylglyoxal derivatives, secondary amines and alkynes under an N 2 atmosphere. 21 This method afforded the efficient synthesis of three-substituted furans in good yields and provided a powerful approach for the preparation of furan derivatives. Meanwhile, Hashmi and co-workers demonstrated a reaction to form 1,2-dicarbonyl-3-enes with the same substrates under AuCl catalysis. 22 Secondary amine mediated alkyne-toallene isomerisation and hydrolysis of the enamine substructure during the work-up delivered the formal hydroacylation products. During our previous work, we found traces of 2-aminobutene-1,4diones formed under aerobic conditions with gold catalysts, so we decided to study this product. Now we wish to introduce a goldcatalysed one-pot, three-component synthesis of 2-aminobutene-1,4-dione derivatives utilising the same substrates (phenylglyoxal derivatives, secondary amine and alkynes) in the presence of H 2 O (Scheme 1).

Gold-catalyzed multicomponent reactions

“…In 2016, Liu and co-workers reported a MCRs of terminal alkynes 13a , amines 13b and glyoxal derivatives 13c in the presence of 5 mol% AuBr 3 , MeOH/H 2 O as a solvent and an O 2 balloon at 50 °C to afford 2-aminobutene-1,4-diones 13d (Scheme 13). 40…”

“…In 2016, Liu and co-workers reported a MCRs of terminal alkynes 13a, amines 13b and glyoxal derivatives 13c in the presence of 5 mol% AuBr 3 , MeOH/H 2 O as a solvent and an O 2 balloon at 50 °C to afford 2-aminobutene-1,4-diones 13d (Scheme 13). 40 Later, Tokuyama and co-workers demonstrated the goldcatalyzed domino reactions for the synthesis of substituted anilines 14d using terminal alkynes 14a, acetal amide 14b and internal alkynes 14c (Scheme 14). 41 The same group reported the synthesis of pyrroles 14e using terminal alkynes 14a and acetal 14b under gold catalysis.…”