Molecules 2012, 17, 2812-2822; doi:10.3390/molecules17032812
Efficient Synthesis of β-Enaminones and β-Enaminoesters
Catalyzed by Gold (I)/Silver (I) under Solvent-Free Conditions
Ming Zhang 1, Ablimit Abdukader 1,2, Yong Fu 1 and Chengjian Zhu 1,3,*
1 State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering,
Nanjing University, Nanjing 210093, China; E-Mails: email@example.com (M.Z.);
firstname.lastname@example.org (A.A.); email@example.com (Y.F.)
2 School of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, China
3 State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
* Author to whom correspondence should be addressed; E-Mail: firstname.lastname@example.org;
Received: 15 January 2012; in revised form: 16 February 2012 / Accepted: 17 February 2012 /
Published: 6 March 2012
Abstract: An efficient method for the synthesis of β-enaminones and β-enaminoesters
using a combination of [(PPh3)AuCl]/AgOTf as catalyst has been developed. The reaction
between 1,3-dicarbonyl compounds and primary amines was carried out under solvent-free
conditions with low catalyst loading in good to excellent yields at room temperature.
Keywords: gold; solvent-free; amines; β-enaminones; β-enaminoesters
β-Enaminones and β-enaminoesters are highly useful building blocks [1–3], which can be further
transformed into valuable natural therapeutic and biologically active compounds such as
anticonvulsivant [4,5], anti-inflammatory , and antitumor agents [7,8]. Moreover, they are useful
intermediates for the preparation of aminoesters , α,β-aminoacids [10,11], peptides ,
quinolines [13,14], azocompounds [15,16] and alkaloids [17–19]. Owning to their significances in
organic synthesis, considerable efforts have been dedicated to prepare β-enaminones and β-enamino-
esters. One of the most straightforward methods is condensation between 1,3-dicarbonyls and amines
under reflux conditions . Other improved methods for this amination reaction were successively
Molecules 2012, 17
developed [21–34]. However, in these procedures, the long reaction time, high reaction temperatures,
and high catalyst loadings required could limit their further applications in organic synthesis.
Gold (I) and gold (III) salts have emerged as versatile catalysts to facilitate new carbon-carbon or
carbon-heteroatom bond formation in a variety of reactions [35–38]. In 2003, Arcadi reported that gold
(III) derivatives could catalyze the condensation reaction of 1,3-dicarbonyls and ammonia/amines ,
however, when the aromatic amine had been involved in the reaction only 60% yield was obtained.
With increasing attention being paid to economically simple and environmentally safe methods, the
recent trends in organic reaction are oriented to solvent-free conditions [39–41]. Herein, we report a
practical method for the synthesis of β-enaminones and β-enaminoesters under solvent-free conditions
by using [(PPh3)AuCl]/AgOTf as catalyst with lower catalyst loading at room temperature (Scheme 1).
Scheme 1. Gold (I)/silver (I) catalyzed enamination of β-dicarbonyl compounds.
2. Results and Discussion
Initially, the reaction between acetylacetone and 4-methoxyaniline was carried out without catalyst
under solvent-free conditions at room temperature for 2 h; only 25% yield of the desired product could
be obtained (Table 1, entry 1). The salt (PPh3)AuCl (1 mol%) indicated moderate catalytic activity
(33% yield) (Table 1, entry 2), while the silver salt AgOTf (1 mol%) afforded a lower yield (28%
yield) (Table 1, entry 3). Surprisingly, by combining (PPh3)AuCl (1 mol%) with AgOTf (1 mol%) as
cocatalyst, the product could be obtained in higher yield (98%) than when a single salt was used
(Table 1, entry 4), so (PPh3)AuCl/AgOTf was chosen as a promising catalyst for the reaction. The
reaction was found to be sluggish when dichloromethane (DCM, 1 mL) was chosen as solvent
(Table 1, entry 5). Various amines were examined in this enamination reaction with acetylacetone, and
the corresponding β-enaminones were obtained in excellent yields (85%–98%). The results are listed
in Table 2.
Table 1. Screening of the reaction conditions for the enamination a.
a Reaction conditions: See typical procedure; b Isolated yield; c The reaction was carried out in DCM.
(PPh3)AuCl + AgOTf
(PPh3)AuCl + AgOTf
Yield (%) b
Molecules 2012, 17
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Sample Availability: Samples of the compounds are available from the authors.
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