One-Pot Double Suzuki−Miyaura Couplings: Rapid Access to Nonsymmetrical Tri(hetero)aryl Derivatives

Abstract

We describe a one-pot, simultaneous Suzuki-Miyaura cross-coupling of two different aryl boronic acids with symmetrical dibromo aryl and heterocyclic substrates to give as major products the unsymmetrical disubstituted tri(hetero)aryl derivatives. Yields of unsymmetrical dicoupled products were generally in the 52-75% range. This methodology is particularly suited to the generation of chemical libraries, as well as to the synthesis of biologically active or natural product analogs.

Chemoselective oxidation of aryl organoboron systems enabled by boronic acid-selective phase transfer

“…, B(OH) 2 vs. BPin in the studies above); however, this represents the first chemoselective oxidation of two ostensibly equivalent boronic acid species based on subtle differences in the substitution of the pendant aryl unit. 33,34 …”

Selective Suzuki–Miyaura Monocouplings with Symmetrical Dibromoarenes and Aryl Ditriflates for the One‐Pot Synthesis of Unsymmetrical Triaryls

“…[7] McNulty conducted a similar study on dichlorobenzenes, [8] and the Langer group developed various sets of conditions for the selective coupling of polyhalogenated substrates. [11] This latter approach can be extremely valuable for accessing biologically interesting targets such as lamellarin A4 and G, [12] ningalin B, [13] and their analogs (Figure 1). [11] This latter approach can be extremely valuable for accessing biologically interesting targets such as lamellarin A4 and G, [12] ningalin B, [13] and their analogs (Figure 1).…”

Synthesis of Conjugated Tri(hetero)aryl Derivatives Based on One-Pot Double Suzuki-Miyaura Couplings Using Bifunctional Dipotassium Phenylene-1,4-Bis(Trifluoroborate)

“…24 Of note, a one-pot double SM coupling of symmetrical dibromoaryl and heterocyclic substrates with two different aryl boronic acids, simultaneously present in the reaction mixture, has recently been accomplished by taking advantage of the difference in reactivity of each boronic acid. 25 In principle, in order to achieve a chemoselective aromatic substitution in the highly symmetrical salt 2, the two borate functions should undergo hydrolysis, in the basic reaction medium, at a different rate, before coupling reaction occurs. To this end, hydrolysis of 2 was investigated by 1 H NMR spectroscopy (room temperature) in a solely deuterated aqueous medium in the presence of K 2 CO 3 (3 equiv) as a function of time.…”