Palladium-Catalyzed, Direct Boronic Acid Synthesis from Aryl Chlorides: A Simplified Route to Diverse Boronate Ester Derivatives

Abstract

Although much current research focuses on developing new boron reagents and identifying robust catalytic systems for the cross-coupling of these reagents, the fundamental preparations of the nucleophilic partners (i.e., boronic acids and derivatives) has been studied to a lesser extent. Most current methods to access boronic acids are indirect and require harsh conditions or expensive reagents. A simple and efficient palladium-catalyzed, direct synthesis of arylboronic acids from the corresponding aryl chlorides using an underutilized reagent, tetrahydroxydiboron B 2 (OH) 4 , is reported. To insure preservation of the carbon-boron bond, the boronic acids were efficiently converted to the trifluoroborate derivatives in good to excellent yields without the use of a workup or isolation. Further, the intermediate boronic acids can be easily converted to a wide range of useful boronates. Finally, a two-step, one-pot method was developed to couple two aryl chlorides efficiently in a Suzuki-Miyaura-type reaction.The Suzuki-Miyaura cross-coupling reaction has become of immense utility and thus importance,1 , 2 and yet there does not exist a simple, robust, catalytic, and functional group tolerant method that provides direct access to the boronic acid, with straightforward conversion to related derivatives. Thus, arylboronic acids are normally accessed by hydrolysis of boronate esters, and consequently many other boronic acid derivatives (e.g., organotrifluoroborates) are derived ultimately from these same boronate esters. The boronate esters can be accessed in a number of ways, including iridium-catalyzed C-H activation with bis(pinacolato)diboron3 and transmetalation from reactive organometallics.4 The harsh reaction conditions used in the latter approach severely limit functional group incorporation into the boronic acid derivatives.5 Another common method makes use of bis(pinacolato)diboron or related reagents to access arylboronates catalytically according to Miyaura's widely used protocol.6 -12 When boronic acids are the targets required in any of these protocols, the boronate esters must be converted by way of oxidation,13 hydrolysis,14 reduction, 15 or transesterification. 16 These methods are inherently inefficient both in terms of atom economy and step economy, employ harsh reaction conditions (NaIO 4 , aq HCl, LAH, diethanolamine, BBr 3 ), or require the use of excess polymer-supported boronic acid. 16,17 Further, the transformation of pinacol boronate esters to the analogous trifluoroborates often suffers from difficulties in purification, rendering these protocols exceedingly tedious. 18,19 In this communication, the development of the first direct synthesis of boronic acids via palladium-catalyzed cross-coupling of aryl chlorides with tetrahydroxydiboron B 2 (OH) 4 (1) is outlined. [20][21][22][23] This protocol allows the direct synthesis and isolation of arylboronic acids and also permits the preparation of trifluoroborates and diverse boronate analogs without the use of highly reactive organomet...

Oxidative Addition of Boron Trifluoride to a Transition Metal

“…Also of direct relevance to B À F bond activation is the growing interest in organofluoroborates as substrates for the widely-used Suzuki-Miyaura coupling protocol and their attendant possibilities for application in organic and pharmaceutical chemistry. [10] In the course of our studies on the zerovalent platinum species [(Cy 3 P) 2 Pt] (1) and related electron-rich late-transition-metal complexes, we have explored the limits of the Lewis basicity of 1 and its pronounced propensity to oxidatively add BÀCl and BÀBr bonds. [11,12] By extension, naturally, we became interested in its reactivity towards fluoroboranes.…”

A Flow-Based Synthesis of Telmisartan

“…The boron species is then inserted at the 6-position of the benzimidazole. We elected to use diboronic acid [9] in order to improve the overall atom economy of this procedure. We were able to complete the transformation with a more cost effective catalyst (PdCl 2 (PPh 3 ) 2 ) while reducing the catalyst loading to 3 mol%.…”

Transition Metal-Mediated and Metal-Catalyzed Carbon–Fluorine Bond Formation

“…In large part due to the success of palladium-catalyzed arene cross-coupling reactions between carbon and a wide variety of other atoms -in particular B [88,89], C [84,90], N [91][92][93][94], and O [95,96] -Pd-mediated and Pd-catalyzed arene fluorination has been targeted as a promising approach. Early work in this field was primarily led by Grushin, who began exploring the synthesis and reactivity of the first mononuclear arylpalladium (II) fluoride complexes (Fig.…”

“…In 2008, the Ritter group reported a regioselective fluorination of arylboronic acids using Selectfluor and a stoichiometric palladium complex (Fig. 59) [88,89,151]. The two-step reaction sequence proceeded by transmetallation of the arene substrate from boron to palladium, followed by oxidation to afford the aryl fluoride product.…”