Three-Component Coupling of Aldehydes, Aminopyrazoles, and Sulfoxonium Ylides via Rhodium(III)-Catalyzed Imidoyl C–H Activation: Synthesis of Pyrazolo[1,5-a]pyrimidines

Abstract

An efficient, three-component strategy for Rh(III)-catalyzed annulation of readily available 3-aminopyrazoles, aldehydes, and sulfoxonium ylides to give diverse pyrazolo[1,5-a]pyrimidines is disclosed. The reactions were performed under straightforward benchtop conditions using microwave heating with short reaction times. Good yields were obtained for a number of substituted aminopyrazoles and a very large variety of aromatic and heteroaromatic aldehydes, including those incorporating electron-withdrawing, electron-donating, basic nitrogen, halide and acidic functionality. Ester and methoxy functionalities could also be directly installed on the pyrimidine ring by employing ethyl glyoxylate and trimethyl orthoformate in place of the aldehyde, respectively. Additionally, a range of sulfoxonium ylides provided products in good yields to establish that aryl, heteroaryl, and branched and unbranched alkyl substituents can be introduced with this reagent. Finally, the first use of a formyl sulfoxonium ylide in a chemical transformation enabled the preparation of products with only a single substituent on the pyrimidine ring as introduced by the aldehyde coupling partner. For the formyl ylide, a one-pot, stepwise reaction sequence was used to prevent competitive condensation of the formyl group with the aminopyrazole.

Pyrazolo[1,5-a]pyrimidines-based fluorophores: a comprehensive theoretical-experimental study

“…Among the synthetic procedures available for the preparation of diverse pyrazolo [1,5-a]pyrimidine (PP) derivatives, 7,[12][13][14][15][16][17][18][19][20][21] the strategy involving the cyclocondensation of NH-3-aminopyrazoles with b-dicarbonyl compounds or other 1,3-bis-electrophiles (e.g., alkoxymethylene-b-dicarbonyl compounds, a,b-unsaturated systems, b-enaminones, b-ketonitriles, b-enaminonitriles, among others) has been the most frequently studied due to its excellent performance. This synthetic approach allows key structural modications at all the peripheral positions during ringconstruction and through subsequent functionalization steps.…”

“…This synthetic approach allows key structural modications at all the peripheral positions during ringconstruction and through subsequent functionalization steps. 7,[12][13][14][15][16][17][18][19][20][21] It is important to note that the theoretical calculations are an important tool for examining the electronic and reactivity properties of some interesting uorophores. [22][23][24][25] For example, the excited-state intramolecular proton transfer (ESIPT) process, 22 absorption and emission transitions, 23 aggregationcaused quenching mechanism, 24 and other crucial chemical properties of the uorescent molecules 25 have been investigated.…”

Palladium-Catalyzed Synthesis of α-Carbonyl-α′-(hetero)aryl Sulfoxonium Ylides: Scope and Insight into the Mechanism

“…Flash chromatography: Merck silica gel 60 (230-400 mesh). NMR: the 1 H, 13 1 and 47 17 were prepared by the reported procedures.…”

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold

“…Likewise, Ellman et al [ 59 ] designed a method based on catalysis with Rh complexes to obtain the pyrazolo[1,5- a ]pyrimidines 58a–at through the multicomponent reaction of aldehydes 55 , aminopyrazoles 56 , and sulfoxonium ylides 57 ( Scheme 18 ). The synthesis of 58 was suitable for aldehydes with electron-donating groups (EDGs), heteroaryl, and haloaryl; however, enolizable aldehydes proved difficult substrates.…”