Chemoselective Coupling of 1,1-Bis[(pinacolato)boryl]alkanes for the Transition-Metal-Free Borylation of Aryl and Vinyl Halides: A Combined Experimental and Theoretical Investigation

Herein, we describe the development of a short, simple, and efficient synthesis of amino‐ and hydroxymethyl‐substituted benzoxaboroles. The key step in our strategy was the early stage incorporation of the boron by the borylation of an aniline. The formed boronates were then elaborated to the final products in two additional steps, usually in good yields. The synthetic sequence was amenable to be performed on a preparative scale and 4‐amino benzoxaborole 4b and 6‐hydroxymethyl benzoxaborole 10c have been prepared, without any significant decrease in the overall yield. The amino and hydroxymethyl present at the molecules are useful for further elaboration and/or conjugation to bioactive molecules and therefore we believe that this method should be useful in the development of new compounds for Medicinal Chemistry.

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“…2‐(2,3‐Dimethylphenyl)‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane (8a) : Orange oil. Yield: 339 mg (73 %).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Amino‐ and Hydroxymethyl Benzoxaboroles: Prominent Scaffolds for Further Functionalization

et al. 2019

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“…In line with their continuous endeavor utilizing 1 in organic synthesis, the groups of Cho and Baik investigated the chemoselective borylation of aryl and vinyl halides (I, Br) employing 1 (R 1 = R 2 = H or R 1 = H, R 2 = CH 3 ) as the source of boron (Scheme (c)) . As a rare example of a transition‐metal‐free borylation reaction, Cho and Baik's method exhibited good compatibility with the presence of a broad range of organohalides.…”

Section: Methodsmentioning

confidence: 99%

Development of Transition‐Metal‐Free Carbon–Carbon and Carbon‐Boron Bond‐Forming Reactions by Utilizing 1,1‐Bis[(Pinacolato)Boryl]Alkanes

Kim

Lee

2017

Bulletin Korean Chem Soc

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Organoboranes are one of the most versatile reagents and intermediates in organic synthesis, enabling a wide variety of synthetic transformations.1 Due to their stability, easy accessibility and environmentally benign nature, numerous classes of organoboron reagents have been prepared and utilized under both stoichiometric and catalytic conditions ever since the laboratory preparation of triethylborane by Frankland in 1859. 2 In particular, the boron reagents have enjoyed widespread use as coupling partners in palladium-, nickel-, or copper-catalyzed cross coupling reactions such as Suzuki-Miyaura reaction 3 and Chan-Evans-Lam reaction. 4In 2010, Shibata and Endo elegantly introduced 1,1-bis [(pinacolato)boryl]alkanes (1) as a new class of boronbased coupling reagent in their chemoselective and regiospecific Suzuki-Miyaura reaction of aryl halides, which operate under palladium catalysis.5 Following this seminal work, 1 have attracted considerable attention from the synthetic community and various catalytic and non-catalytic, chemo-and enantioselective C C bond-forming reactions have been developed, using 1 as the key reagent. 6Morken and co-workers in 2014 reported the first example of the alkoxide-promoted deborylative alkylation of 1 with alkyl halides (Scheme 1(a)).7a This transformation provided access to primary, secondary, and tertiary alkylboronic esters in good to excellent yields with high chemoand diastereoselectivity, and features broad substrate scope including tolerance for geminal bis(boryl)cyclopropanes. Remarkably, an intramolecular version of this deborylative alkylation provides an efficient route to carbocyclic organoboronates with three to seven-membered ring sizes, which are not readily accessible by other means. Mechanistic studies indicated that an α-boryl carbanion B could be generated in situ upon reaction of 1 with the metal alkoxide through chemoselective mono deborylation of an ate complex A, accompanied by liberation of tBuOBpin (Scheme 1(a)). The intermediary presence of boron alkylidene B 0 specie, which formed presumably due to the enhanced π-bonding interaction between the negatively charged carbon atom and the Lewis-acidic threecoordinated boron, was also supported by spectroscopic studies. Very recently, the same group also disclosed deborylative cyclization reaction of 1 bearing a tethered alkene. It was proposed that this unusual transformation proceeds via a non-concerted stepwise [2 + 2] cycloaddition reaction between the tethered alkene and a boron alkylidene. In 2016, the group of Cho independently developed regioselective alkylation of quinoline and pyridine N-oxides using 1 (R 1 = alkyl, R 2 = H) as alkylating agents (Scheme 1(b)). 8a The optimal conditions for methylation included the use of NaOCH 3 as base and toluene as the solvent in presence of an excess amount of 1 (R 1 = R 2 = H) at an elevated temperature of 80 C. Instead of expected 2-(borylmethyl)heteroarenes, the deoxygenated 2-methylated quinoline and pyridine derivatives were obtained as a single product...

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“…Conventional methods for their preparation are based on either reactive organometallic reagents or transition-metal-mediated processes [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]. Recently, great effort has been made towards the development of transition-metal-free methods with high chemoselectivity or regioselectivity and environmental sustainability [38,39,40,41,42,43,44,45,46,47,48]. The transition-metal-free catalyzed borylation reaction of alkynes and alkenes offers an attractive method for generating valuable organoboron compounds.…”

Section: Introductionmentioning

confidence: 99%

Recent Synthesis Developments of Organoboron Compounds via Metal-Free Catalytic Borylation of Alkynes and Alkenes

et al. 2018

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Diboron reagents have been traditionally regarded as “Lewis acids”, which can react with simple Lewis base to create a significant nucleophilic character in one of boryl moieties. In particular, bis(pinacolato)diboron (B2pin2) reacts with simple Lewis bases, such as N-heterocyclic carbenes (NHCs), phosphines and alkoxides. This review focuses on the application of trivalent nucleophilic boryl synthon in the selective preparation of organoboron compounds, mainly through metal-free catalytic diboration and the β-boration reactions of alkynes and alkenes.

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Chemoselective Coupling of 1,1-Bis[(pinacolato)boryl]alkanes for the Transition-Metal-Free Borylation of Aryl and Vinyl Halides: A Combined Experimental and Theoretical Investigation

Cited by 59 publications

References 86 publications

Synthesis of Amino‐ and Hydroxymethyl Benzoxaboroles: Prominent Scaffolds for Further Functionalization

Synthesis of Amino‐ and Hydroxymethyl Benzoxaboroles: Prominent Scaffolds for Further Functionalization

Development of Transition‐Metal‐Free Carbon–Carbon and Carbon‐Boron Bond‐Forming Reactions by Utilizing 1,1‐Bis[(Pinacolato)Boryl]Alkanes

Recent Synthesis Developments of Organoboron Compounds via Metal-Free Catalytic Borylation of Alkynes and Alkenes

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