One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

Abstract

SummaryA novel one-pot four-component synthesis of pyrimidyl- and pyrazolylazulenes through the use of glyoxylation–decarbonylative alkynylation–cyclocondensation sequences starting from azulene or guaiazulene as substrates, gives rise to the formation of the target compounds in moderate to good yields.

Selective Decarbonylation via Transition-Metal-Catalyzed Carbon–Carbon Bond Cleavage

“…On the other hand, most of the cases described herein require relatively harsh conditions (>130 °C) for the completion of the reaction and this is usually incompatible in multistep syntheses. Although, various previous attempts, such as the generation of an unstable acyl-metal intermediate, ,, the exploration of novel ligand and additives, or the modulation of the rate of reductive elimation by tuning the electronic synergy of the substrates, , provided new insights into the decarbonylative step under mild conditions. The design of more efficient catalyst systems (e.g., catalysts with high TONs and TOFs) and milder reaction conditions still continues to be an important issue in this area.…”

“…An alternative alkynyl coupling using α-dicarbonyl chlorides was achieved by Müller et al, where indole-3-glyoxylyl chlorides 53 were coupled with terminal alkynes to produce alkynones, using Pd­(OAc) 2 and CuI as cocatalysts (Scheme ). , The proposed mechanism involved the initial oxidative addition of Pd to the C­(acyl)–Cl bond of 53 to form adduct 54 , which underwent decarbonylation and transmetalation with copper acetylide 55 to form acyl-alkynyl-Pd complex 56 ; subsequent reductive elimination afforded product 57 . A one-pot strategy with the in situ formation of indole-3-glyoxylyl chlorides was also achieved. , …”

“… , The proposed mechanism involved the initial oxidative addition of Pd to the C­(acyl)–Cl bond of 53 to form adduct 54 , which underwent decarbonylation and transmetalation with copper acetylide 55 to form acyl-alkynyl-Pd complex 56 ; subsequent reductive elimination afforded product 57 . A one-pot strategy with the in situ formation of indole-3-glyoxylyl chlorides was also achieved. , …”

“…A one-pot strategy with the in situ formation of indole-3-glyoxylyl chlorides was also achieved. 123,124 In terms of C−C bond forming reactions using the decarbonylative strategy, alkenes have also proved to be practicable coupling partners. The first decarbonylative Heck reaction of acyl chlorides was discovered by Blaser and Subsequently, reductive elimination of 64 released the desired arylated product 65.…”

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

“…Due to their general importance (e.g. as biologically active compounds) the development of efficient protocols for the preparation of functionalized pyridine [10–20] and pyrimidine derivatives [21–33], in particular by MCRs, is of permanent high interest. In the course of exploring the reactivity of alkoxyallenes and their utilization as C-3 building blocks [34–37] our group developed a highly flexible method to synthesize β-alkoxy-β-ketoenamides of type 1 that are remarkably versatile cyclization precursors for the synthesis of functionalized heterocycles such as 4-hydroxypyridines [38–44], furopyridines [45], 5-acetyloxazoles [46–47], pyrimidines [43,48–49] and their corresponding N -oxides [50] (Scheme 1).…”