Zn(II)-Catalyzed Addition of Aromatic/Heteroaromatic C(sp²)–H to Azoalkenes: A Polarity-Reversed Arylation of Carbonyl Compounds

Abstract

An umpolung α-(hetero)arylation strategy that involves the Michael-type reaction between electron-rich (hetero)aromatic substrates and azoalkenes is developed. The reaction proceeds under very mild conditions at room temperature and in the presence of inexpensive, nontoxic ZnCl 2 catalyst to provide access to otherwise inaccessible hydrazone structures. Subsequent hydrolysis of these latter to ketones as well as other valuable synthetic transformations to a variety of heterocyclic scaffolds demonstrate the usefulness of this protocol.T he direct installation of an aryl/heteroaryl substituent into the α-position of ketone has proven to be a transformation of great utility in pharmaceutical, agrochemical, and organic synthesis. 1 As result, there is an ever-growing number of methods reported in the literature, 2−4 most of them involving the addition of organometallic species or preformed enolates/ azaenolate to halide/pseudohalide. Despite significant advances in transition-metal-promoted carbon−carbon bond-forming reactions that have been made over the years, a general catalytic arylation/heteroarylation exploiting the C−H bonds of (hetero)aromatics, 5 the most abundant moiety in organic molecules, remains elusive. From the viewpoints of efficiency, sustainability, and atom-and step-economy, the replacement of C−X with C−H bonds that are unreactive under traditional approaches is therefore highly appealing.A polarity-reversed strategy 6 to introduce aryl substituents into the α-position of carbonyl compounds would employ unconventional reactivity patterns, such as azoalkenes 7−9 ("umpoled" carbonyl compounds) in the context of a Michael addition. With this objective, the transformation of a carbonyl

A Metal‐Free C−H Amination‐Based Strategy for N‐Amino Indole Synthesis

“…Then, the other two commonly used hypervalent iodine-(III) oxidants, PIDA and PIFA were tested. PIDA was found to be less effective than PIFA (entries [14][15][16][17][18][19][20][21][22][23]. While the use of fluoroprotic solvents as TFE or HFIP was crucial to achieve high conversion of 1 a, the addition of PivOH or BF 3 •Et 2 O [21] failed to improve the yield of 2 a (entries 24 and 25).…”

“…α-Arylhydrazones 1 a-t were prepared according to our previously reported method with slight modifications. [19] Hydrazones 1 u and 1 v were prepared according to the modified known procedures. [28], [29] Chromatographic purification of compounds was carried out on silica gel (60-200 μm).…”

“…A range of αarylhydrazones corresponding to general structure 1 were prepared via a Zn(II)-catalyzed Michael addition reaction of aromatic C(sp 2 )À H nucleophiles with azoalkenes according to our previously reported method. [19]…”

Umpolung of Enamines: An Overview on Strategies and Synthons

“…39 Recently, the Favi group reported a Zn(II)-catalyzed Michael addition of arenes to azoalkenes (Scheme 6d). 40 This transformation can be viewed as a way to accomplish umpolung arylation of ketones, as the hydrazone moiety can be converted into a carbonyl group. Furthermore, hydrazones resulting from Michael addition to AZA can enter cyclization reactions leading to valuable nitrogen heterocycles.…”

Catalytic Asymmetric Formal [3+2] Cycloaddition of Azoalkenes with 3-Vinylindoles: Synthesis of 2,3-Dihydropyrroles

“…Azoalkenes, also known as 1,2-diaza-1,3-dienes, have proven to be versatile synthetic building blocks in organic chemistry (Attanasi et al, 2002a(Attanasi et al, , 2002b(Attanasi et al, , 2009Attanasi and Filippone, 1997;Lopes et al, 2018;Wei et al, 2019). Their characteristic 1,3-conjugate systems have been utilized synthetically; azoalkenes were shown to be a valuable acceptor in 1,4-conjugate additions, displaying excellent reactivity toward a wide variety of nucleophiles (Attanasi et al, 2011a(Attanasi et al, , 2011b(Attanasi et al, , 2012(Attanasi et al, , 2013a(Attanasi et al, , 2013bCiccolini et al, 2019;Mantenuto et al, 2015;Miles et al, 2015;Preti et al, 2010). Another attractive synthetic application of azoalkenes is the cycloaddition reaction, which serves as a powerful strategy for the construction of nitrogencontaining heterocycles.…”