Abstract:A novel synthesis of polyfunctionalised pyridones, structurally related to cardiotonic agent milrinone is described. The procedure consists of an Ugi four-component reaction of 3-formylchromones, followed by a base-promoted ring-opening/ring-closing process. Variation of three of the four components in the Ugi reaction allows access to the final products with a combinatorial distribution of substituents.
“…The conditions for conduction Ugi reaction is followed according to literature procedure that was reported by Marcaccini, S. 9 We also studied the efficiency of the reaction of chromone based Ugi adduct with triphenyl phosphine under variable conditions. Later we developed a microwave conditions for Ugi reactions here for this we took a substrates for model reaction.…”
The development of efficient methods for the synthesis of heterocyclic compounds is always of great importance for chemists. In this perspective, we describe a general approach for the synthesis of functionalized heterocyclic compounds via Ugi MCR with 3-formyl chromone, amine, 2-chloro acetic acid and isocyanide followed by intramolecular ylide initiated Michael reaction, In this case, the reaction proceeds via in-situ generated phosphonium salt that give scope in formation of novel stable heterocyclic ylides. We especially emphasize the importance of tuning the Ugi adduct for the points of molecular diversity by designing intramolecular ylide initiated Michael reaction with chromone based moiety as Michael acceptor, 2-chloro acetic acid in Ugi reaction that helps for in situ generation of phosphonium salt that allows formation of a different class of heterocyclic compounds.
“…The conditions for conduction Ugi reaction is followed according to literature procedure that was reported by Marcaccini, S. 9 We also studied the efficiency of the reaction of chromone based Ugi adduct with triphenyl phosphine under variable conditions. Later we developed a microwave conditions for Ugi reactions here for this we took a substrates for model reaction.…”
The development of efficient methods for the synthesis of heterocyclic compounds is always of great importance for chemists. In this perspective, we describe a general approach for the synthesis of functionalized heterocyclic compounds via Ugi MCR with 3-formyl chromone, amine, 2-chloro acetic acid and isocyanide followed by intramolecular ylide initiated Michael reaction, In this case, the reaction proceeds via in-situ generated phosphonium salt that give scope in formation of novel stable heterocyclic ylides. We especially emphasize the importance of tuning the Ugi adduct for the points of molecular diversity by designing intramolecular ylide initiated Michael reaction with chromone based moiety as Michael acceptor, 2-chloro acetic acid in Ugi reaction that helps for in situ generation of phosphonium salt that allows formation of a different class of heterocyclic compounds.
“…Here again, a simple aromatic group can also sufficiently stabilise the peptidyl anion, making further cyclisation to heterocyclic products possible. Gómez-Montaño and El Kaïm were able to cyclise in this way the cyanoacetic acid-derived Ugi adducts ( 382 ), previously prepared by Marcaccini [ 124 – 127 ], to give aminopyrrolinone derivatives ( 383 ; Scheme 75 ) [ 128 ]. Scheme 75 Gómez-Montaño—El Kaïm synthesis of aminopyrrolinones …”
Section: Post-condensation Transformations Of Passerini and Ugi Adductsmentioning
confidence: 99%
“…In continuation with these post-Ugi transformations, Marcos et al synthesised the Ugi adducts ( 670 ) of 3-formylchromones ( 669 ) with cyanoacetic acid ( 381 ), amines ( 114 ) and isocyanides ( 31 ). Treatment of these adducts ( 670 ) with KOH in methanol led to a ring-opening/ring-closing process that produced efficiently polyfunctionalised pyridones ( 671 ) related to cardiotonic agent milrinone (Scheme 140 ) [ 127 ]. Scheme 140 Synthesis of milrinone analogues …”
Stefano Marcaccini was one of the pioneers in the use of isocyanide-based multicomponent reactions in organic synthesis. Throughout his career at the University of Florence he explored many different faces of isocyanide chemistry, especially those geared towards the synthesis of biologically relevant heterocycles. His work inspired many researchers who contributed to other important developments in the field of multicomponent reactions and created a school of synthetic chemists that continues today. In this manuscript we intend to review the articles on isocyanide multicomponent reactions published by Dr. Marcaccini and analyse their influence on the following works by other researchers. With this, we hope to highlight the immense contribution of Stefano Marcaccini to the development of isocyanide chemistry and modern organic synthesis as well as the influence of his research on future generations. We believe that this review will not only be a well-deserved tribute to the figure of Stefano Marcaccini, but will also serve as a useful inspiration for chemists working in this field.
Graphical abstract
“…Thus, MCR involving isocyanides (IMCRs), such as the Passerini three-component condensation (P3CC; Scheme 1) [13] and the Ugi four-component condensation (U4CC; Scheme 1) [14], are extensively used to synthesize diversely functionalized substituted α-acyloxy-and α-acylamino amides, respectively [15][16][17]. Further structural diversity can be achieved through a wide variety of postcondensation transformations [18][19][20][21][22][23][24][25][26][27][28][29][30][31] or by the replacement of one of the reactant components with a new reagent that mimics its reactivity and chemical behavior [12]. We have recently discovered that enols can be used as acid components in Passerini-and Ugi-type multicomponent condensations [32][33][34][35].…”
In continuation of our recent research on the development of novel multicomponent reactions with isocyanides, we have used, for the first time, enols as the acid components in Ugi- and Passerini-type reactions. Thus, electron-poor pyrrolidinodiones react with aldehydes, amines, and isocyanides to give the enaminic four-component adducts. Conversely, in the absence of the amine component, careful control of the reaction conditions allows the involvement of one or two molecules of isocyanide to afford, selectively, either Passerini-type or pseudo-enol-Ugi-type products. These unprecedented condensations of isocyanides, aldehydes, amines, and 4-substituted pyrrolidine-2,3-diones constitute an excellent strategy for the preparation of new biologically relevant pyrrolidinones having peptidic or pseudo-peptidic groups on carbon 3.
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