Recent Advances in the Functionalization of Azulene Through Pd‐Catalyzed Cross‐Coupling Reactions

Abstract

Azulene derivatives have important physical and physicochemical features, as well as advantageous biological qualities. The metal‐catalyzed processes have proven to be a highly practical method for azulene functionalization. The development in the synthesis of azulene derivatives, including (aryl)heteroaryl‐substituted and hetero‐fused azulene derivatives, through Pd‐catalyzed coupling techniques over the previous two decades is discussed in this research. Alkyl‐, alkenyl‐, and alkynylazulenes synthesized via Pd‐catalyzed cross‐coupling processes are also included.

Direct Access to Functionalized Azulenes and Pseudoazulenes via Unconventional Alkyne Cyclization Reactions

“…Typical cisinsertion of a second alkyne into alkenyl palladium bond followed by dearomative spiroannulation gives the intermediate 33 with a cyclopentadiene ring. After that, the [1,5]-alkenyl migration on the cyclopentadiene moiety yields intermediate 34, a complex formed between the borylated azulene and Pd(II). Finally, iodide-assisted PdÀ B elimination converts 34 to the final product and releases the PdÀ Bpin catalyst at the same time.…”

“…In 2013, during the synthesis of [5]helicenes 43 with a substituent exclusively on the interior side of the helix by transition metal-catalyzed cycloisomerization, Usui and coworkers observed the azulene-fused helicenes 44 as the minor products when PtCl 2 as the catalyst (Scheme 13). [28] Formally, one carbon of the alkyne inserts into the pendant benzene ring.…”

“…In light of transition metal-catalyzed reactions of the benzenoid compounds, great advances in direct functionalization of azulene beyond electrophilic or nucleophilic substitutions have been made over the last decades. [5] And these transition metal-catalyzed new reactions afford the azulene skeleton decorated by carbon-and a variety of heteroatomcentered substituents, some of which are hardly available by known methods, providing versatile synthons for the more sophisticated azulene derivatives. However, these reactions are restricted by low natural abundance, high cost, and difficulty in selective modification of azulene.…”

Efficient Synthesis and Structural Analysis of Chiral 4,4′‐Biazulene

“…1,1′‐Biazulene with its chiral axis on the five‐membered rings exhibits less hindered rotation around the C1−C1′ bond at room temperature, [9] but introducing the bulky substituents into appropriate positions to increase the rotational barrier endows 1,1′‐biazulene derivatives with chirality and characteristic functions [10] . 1,4′‐Biazulene substituted by a pivaloyloxy group at the 1′‐position was synthesized, but its axial chirality was not studied [8e,11] . In stark contrast to them, 4,4′‐biazulene ( 1 ) with its chiral axis on the seven‐membered rings has the possibility to exhibit the hindered rotation around the C4−C4′ bond.…”

Recent advances in the functionalization of azulene through Rh‐, Ir‐, Ru‐, Au‐, Fe‐, Ni‐, and Cu‐catalyzed reactions

“…In this regard, we recently detailed current progress in Pd-catalyzed azulene functionalization (Figure 1). [9,10] Palladium-catalyzed Suzuki-Miyaura cross-coupling of organoboranes and the Stille-Migita reaction of organostannanes were included in our recent review, as were C C bondforming reactions by Hiyama (Si), Kumada-Tamao-Corriu (Mg), Sonogashira (Cu and C(sp) atoms), and Negishi (Zn, Al, and Zr). [11,12] Pd-catalyzed direct arylation reaction between an organic (hetero)aromatic halide and a (hetero)arene containing at least one Dedicated to the memory of Professor Klaus Hafner C(sp 2 ) H bond, which does not require the use of an organometallic reagent, was also reviewed.…”