Synthesis of poly-functionalized pyrazoles and pyridazines from nitrobutadienes: an interesting dichotomy of practical relevance

Densely Functionalized 2‐Methylideneazetidines from Nitrodienic Building Blocks

“…Thus, both the electronic and stereoelectronic drawbacks of path a would be overcome. Moreover, the intermediacy of the aza‐Michael adduct could also contribute to justify the observed formation of pyrroles 8 or 9 as competitive secondary or primary products in fluorinated solvents: Thus, adduct 14 could undergo an alternative, although “disfavored”, 5‐ endo‐trig cyclization, completed by MeSO 2 H elimination (formally an overall S N V) to give the dihydropyrrole 15 , the latter eventually aromatizing by either base‐induced elimination of nitrous acid or dehydrogenation (most likely performed by the same nitrous acid/nitrite ion released into the reaction mixture[11a], ). Polyfluoro alcohols are well known hydrogen donors for hydrogen bonds that catalyze, for example, conjugated additions; here, they could play a role in stabilizing the adduct 14 long enough to allow the attainment of the correct arrangement of the reactive sites so as to make the formation of 15 (ring‐closure of the amino group onto C1) competitive with the formation of 7 (ring‐closure onto C2).…”

“…Here we report the results obtained with nitrodienes 6 , characterized by the presence of an additional electron‐withdrawing methoxycarbonyl group, which was introduced to further increase the electrophilicity of the diene moiety in the search for novel reactive behavior. In fact, under otherwise similar conditions to those used for 1 , the additional functional group significantly affects the reactivity of 6 with both secondary and primary amines leading, in the latter case, to the intriguing and unexpected synthesis of azetidines 7 , thus providing an original access to densely functionalized representatives of such small building blocks and, at the same time, an enrichment of the pool of heterocycles obtainable by means of the RORC protocol from nitrothiophenes , …”

An Easy Access to Furan-Fused Polyheterocyclic Systems

“…As a matter of fact, starting from a pioneering report [ 32 ], during our previous studies, while exploring the reactivity of different nucleophiles towards nitrobutadienes generated by an initial ring-opening of nitrothiophenes [ 33 , 34 , 35 ], we obtained a great variety of nitrogen-containing heterocycles, such as methyleneazetidines [ 36 ], pyrroles [ 37 ], pyrazoles [ 38 ], carbazoles [ 39 ], imidazo[1,2- a ]pyridines [ 40 ], and nitroindoles [ 41 ]. However, the involvement of nucleophiles able to generate O-heterocycles, as, for instance, enols, has not been investigated so far.…”

Synthesis of poly-functionalized pyrazoles under Vilsmeier-Haack reaction conditions

“…This heterocycle and its derivatives are important building blocks for organic, bioorganic, pharmaceutical and supramolecular chemistry as well as materials science. [1][2][3][4][5][6][7][8][9] In fact, the pyrazole ring ranks 44 th in a frequency among 351 ring systems found in currently marketed drugs. 10 The incorporation of functional groups into the pyrazolic architecture attracts considerable interest because this modification opens the possibility for further transformations.…”