Palladium-Catalyzed Borylation of Aryl and Heteroaryl Halides Utilizing Tetrakis(dimethylamino)diboron: One Step Greener

Abstract

The palladium-catalyzed borylation of aryl and heteroaryl halides with a novel borylating agent, tetrakis(dimethylamino)diboron [(Me2N)2B-B(NMe2)2], is reported. The method is complementary to the previously reported method utilizing bis-boronic acid (BBA) in that certain substrates perform better under one set of optimized reaction conditions than the other. Because tetrakis(dimethylamino)diboron is the synthetic precursor to both BBA and bis(pinacolato)diboron (B2Pin2), the new method represents a more atom economical and efficient approach to current borylation methods.

One-pot borylation/Suzuki–Miyaura sp2–sp3 cross-coupling

“…20 We were also keen to avoid limiting the scope of the reaction by eliminating ethanol, since we anticipated alkylation of the solvent by the activated alkyl chloride coupling partners and palladium catalysed hydride reduction of functional groups such as nitro and keto which was previously observed under these borylation conditions. 9b Based on work by Molander 10 and Schmidt-Leithoff, 11 we decided on the use of the most atom economical diboron reagent, B2(NMe2)4. Indeed, commercially available B2(NMe2)4 is the synthetic precursor to other more common diboranes such as B2(pin)2 and B2(OH)4, 21 but has not been previously utilised in any one-pot borylation/SM cross-coupling processes.…”

“…Upon addition of aqueous K2CO3, any remaining diborane is destroyed, preventing deleterious side reactions of the diborane and alkyl chloride. 10 Addition of alkyl chloride 2 then allows the SM sp 2 -sp 3 cross-coupling with the in situ generated aryl boronic ester 7, catalysed by the same Pd(0) that mediated the borylation stage, yielding diaryl methanes 3, allyl aryls 4, and α-aryl carbonyl compounds 5. Scheme 4.…”

Synthesis and Suzuki–Miyaura Cross‐Coupling of Enantioenriched Secondary Potassium β‐Trifluoroboratoamides: Catalytic, Asymmetric Conjugate Addition of Bisboronic Acid and Tetrakis(dimethylamino)diboron to α,β‐Unsaturated Carbonyl Compounds

“…A similar solvent trend has been observed in the Miyaura borylation with BBA and tetrakis(dimethylamino)diboron, where improved yields were obtained with MeOH as the solvent. [10a],[10b],[11] Using these conditions, the yield obtained with BBA as the borylating agent is practically the same as that using B 2 (NMe 2 ) 4 , whereas the enantiomeric ratio obtained is the same for both dibora sources. Therefore, these modified conditions were applied to an array of α , β -unsaturated amides (Table 4).…”

“…Recently, tetrahydroxydiboron [10] (bisboronic acid or BBA) and tetrakis(dimethylamino)diboron [11] have been demonstrated to be more sustainable and more atom economical dibora species as compared to bis(pinacolato)diboron (Figure 1). Tetrakis(dimethylamino)diboron is synthesized in a three-step sequence starting from boron tribromide.…”

“…[10a],[10b],[11] BBA can also undergo conjugate additions to α , β -unsaturated carbonyl compounds in a racemic manner. [10c] The goal of the current project was to employ BBA and/or tetrakis(dimethylamino)diboron in the catalytic, asymmetric synthesis of potassium β -trifluoroboratoamides.…”