Efficient Monophosphorus Ligands for Palladium-Catalyzed Miyaura Borylation

Abstract

In combination with the Bedford Pd precursor, the new biaryl monophosphorus ligand 5 was efficient for palladium-catalyzed Miyaura borylation of sterically hindered aryl bromides at low catalyst loadings.

Scope of the Palladium-Catalyzed Aryl Borylation Utilizing Bis-Boronic Acid

“…Through a thorough literature search of heteroaryl boronates synthesized from B 2 Pin 2 or H-BPin, two trends can be found: either the method reported is purely for one functionalized heteroaryl, 50–60 or only a few examples were synthesized under reaction conditions considered under a “general” methods procedure. 14,40,42,44,61–64 Also noteworthy is that the heteroaryls examined in this search are among just a handful of heteroaryl borylated products that can be found in the literature, and there is no publication dedicated solely to the Miyaura borylation of heteroaryls using B 2 Pin 2 . Our findings, coupled with the literature results, provide evidence that a general method for the borylation of hetereoaryls remains elusive, and that each substrate or general class of substrates may need to be treated on a case-by-case basis.…”

Formal Nucleophilic Boryl Substitution of Organic Halides with Silylborane/Alkoxy Base System

“…In addition, the sterically more congested 1-bromo-2,4,6-triisopropylbenzene 2p also reacted to provide the borylation product 3p in excellent yield (92% yield). It is noteworthy that boryl substitution of substrate 2p has been reported as a difficult transformation even using diboron and transition-metal catalysts [9,12,49]. This boryl substitution reaction was also successfully applied to the reaction of alkyl bromide 2q in dioxane at 100 o C to give the corresponding product 3q in good yield with high B/Si selectivity (Scheme 2, total 82% yield, B/Si = 91:9).…”

“…No reaction occurred without the base (entry 2). This reaction proceeded rapidly; requiring only 15 min to reach completion while comparable transition-metal-catalyzed borylations [8,9,11,12], which are conventional methods for production of functionalized aryl boronates, require several hours at 80−100 o C under standard conditions. Ethereal solvents are suitable for this boryl substitution (entries 1 and 3-7).…”

An Efficient Method for Sterically Demanding Suzuki–Miyaura Coupling Reactions

“…To address this issue, a mild base such as potassium phosphate must be employed for these substrates. Although the catalyst Pd/ 1 with K 3 PO 4 as the base proved to be less effective,16 we were pleased that ligand 2 with an anthracenyl moiety17 (Scheme ) was efficient for various functionalized substrates at only 1 mol % Pd loading (Table 3). Functionalities such as aldehyde, ketone, phosphonate, cyano, nitro, or fluoro groups were well tolerable.…”