Rhodium-Catalyzed Synthesis of 2-Aroylpyrimidines via Cascade Heteropolyene Rearrangement

Abstract

A one-step synthesis of cytotoxic 2-aroylpyrimidines by the denitrogenative reaction of 1-tosyl-1,2,3-triazoles with isoxazoles under rhodium catalysis has been developed. According to the density functional theory calculations and control experiments, the disclosed reaction proceeds via the rearrangement of an oxadiazatetraene intermediate involving a cascade of intramolecular aza-Diels−Alder and retro-aza-Diels−Alder reactions. The presence of a substituent at C4 of the isoxazole is a prerequisite for the formation of the pyrimidines.

(1RS,3SR)-1-(4-Methylbenzyl)-7-phenyl-5-oxa-6-azaspiro[2.4]hept-6-en-4-one

“…In this work, we report that the reaction of 4-(4-methylbenzylidene)-3-phenylisoxazol-5-one with diazomethane proceeds as a double methylene transfer, affording a benzyl-substituted cyclopropane spiro-fused with isoxazol-5-one. Note that examples of the double methylene transfer are rarely found in the literature [19][20][21][22], and, to the best of our knowledge, have never been observed in the cyclopropane formation.…”

Synthesis of Functionalized Pyrimidines from Propargylic alcohols and their Derivatives: Two Decades of Developments

“…Conventionally, pyrimidines have been synthesized through a condensation reaction between amidines ( N −C− N fragment) and suitable C‐3 coupling partners such as 1,3‐carbonyl compounds, [6] α , β ‐unsaturated carbonyl compounds, [7] ynones, [8] and so on [9] . Additionally, various transition metal catalysed [Cu, [10a] Ni, [10b] Pd, [10c] Rh, [10d] Au, [10e] Ru, [10f] Ir [10g] and Fe [10h] ] synthetic transformations have also been established for the construction of pyrimidine framework. Very recently employing the alkynones and propargylic derivatives as 3‐carbon atom units for the synthesis of pyrimidine derivatives has attracted the synthetic community [11]…”

Unearthing the Subtleties of Rhodium(II)-Catalyzed Carbenoid Cycloadditions to Furans with an N-Sulfonyl-1,2,3-triazole Probe

“…The use of vinylogous rhodium metallocarbenes as three-carbon synthons is a proven strategy for the synthesis of complex carbon ring systems via formal [4 + 3] and [3 + 2] cycloadditions. − An early example of this type of reactivity is the rhodium-catalyzed reaction of furans 1 with vinyldiazoacetates 2 to form [4 + 3] cycloadducts 3 , which often competes with furan ring opening to form 4 (Scheme ). In recent years, considerable interest has been shown in accessing the carbenes from N -sulfonyl-1,2,3-triazoles, which act as masked diazo functions, alleviating the need to isolate the decomposition-prone alkenyl-diazo moiety. , Despite the high level of interest in N -sulfonyltriazole-derived metallocarbene chemistry, − few methods have been reported for their utilization in cycloaddition reactions for the construction of carbocyclic systems . One explanation for this observation is that donor/acceptor metallocarbenes derived from N -sulfonyltriazoles contain a nucleophilic sulfonyl imine, which often becomes incorporated into the reaction to form heterocycles.…”