Copper‐Catalyzed Monoorganylation of Trialkyl Borates with Functionalized Organozinc Pivalates

Abstract

Organozinc pivalates, a recently developed air-and moisturestable organozinc species, were found for the first time as excellent organometallic species in the monoorganylation of trialkyl borates whereby boronic acids were prepared in high yields. The significant advantage of organozinc pivalates over another previously employed organometallic reagents, e. g., organolithium reagents, Grignard reagents and organozinc halides, is that the generation of multiorganylation byproducts such as borinic acids and trialkylboranes were completely suppressed. Additionally, the in situ generated boronates could be directly arranged into Suzuki-Miyaura type cross-coupling reactions to produce biaryls in high yields.The great success of organylboronic acids and their derivatives in organic synthesis, [1] pharmaceuticals [2] and material chemistry [3] has inspired dramatic synthetic interests [4] on these privileged molecules. Thus, a range of protocols have been developed to convert aryl [5] and alkyl [6] halides, carboxylic acid derivatives, [7] anilines, [8] diaryliodonium salts, [9] arenes, [10] alkenes [11] and quaternary ammonium salts [12] etc. into boronic acids or their esters. However, due to the employment of unaffordable expensive borylating agents or expensive transitional metal catalysts, most of these protocols are rarely employed in the practical boronic acids synthesis. Thus, the conventional approach, the electrophilic trapping of organometallics (generally the lithium reagents, [13] Grignard reagents [14] and organozinc reagents [15] ) with trialkyl borates, still occupies a large portion in modern factory manufacture. The common defects involved in this approach are, cryogenic conditions demanding, poor functional groups tolerance (largely due to high reactivity of organometallics), unavoidable borinic acid and borane byproducts (arise from second and third additions of the organometallic reagents into the borate esters), low isolated yields. To avoid multiple addition of organometallics to borate esters, Wang et al. [14d] reported that bis [2-(N,N-dimethylamino) ethyl] ether could be employed as a ligand to suppress these side reactions. Alternatively, Leermann et al. [14b] reported that excellent yields of boronic acids were obtained via reactions of Grignard's with B(OMe) 3 in the presence of LiCl.Organozinc pivalates [16] are a privileged class of organometallics particularly known to their air-and moisture-stability and broad spectrum of functional groups tolerance. These reagents exhibit excellent reactivity in reactions, e. g., Negishi cross coupling reactions [17] and were successfully used in the synthesis of complex molecules [18] Based on our interests on expanding the applicability of organozinc reagents in organic synthesis, [19] we here first describe a CuI-catalyzed chemospecific borylation of organozinc pivalates with trialkyl borates to afford boronic acids in high yields.Initially, p-TolZnBr·MgCl 2 ·LiCl (2a'), in situ prepared from ptolylbromide (1 a) via magnesium insertion-Z...

Recent Advances in the Preparation of Air Stable Organozinc Pivalates and their Applications in Organic Synthesis

“…Furthermore, under copper catalysis, in situ formed aryl boronates could be directly used in Suzuki-Miyaura cross-coupling with 5 mol% loading of Pd catalyst to give the desired biphenyl derivatives 4 in high yields (Scheme 22). [32] Tüllmann et al reported the synthesis of mono-and bispivaloyloxyzinc acetylide organometallic reagents 47 with improved air and water stability. Mono-pivaloyloxyzinc acetylide smoothly underwent 2 mol% Pd-catalyzed Negishi cross-couplings with aryl iodides or bromides 3 to form the desired (hetero)aryl alkynes 48.…”

Recent Progress in Utilization of Functionalized Organometallic Reagents in Cross Coupling Reactions and Nucleophilic Additions

“…Shen et al 37 reported a practical and efficient coppercatalyzed protocol for constructing the C-B bond from trialkyl borates and air-and moisture-stable organozinc pivalates under mild conditions (THF as solvent at room temperature) (Scheme 35). This method avoided the generation of by-products, such as borane, and provided a more practical method for boronic ester synthesis in high yields.…”

Magnesium promoted autocatalytic dehydrogenation of amine borane complexes: A reliable, non-cryogenic, scalable access to boronic acids

“…11 B NMR (96 MHz, acetone-d 6 ): δ (ppm) 28.9. 13 C NMR (75 MHz, acetone-d 6 ): δ (ppm) 161.7, 135.8, 112.9, 54.4 B-2-Naphthalenylboronic acid [32316-92-0] 6h 32 670 mg of (Naphthalen-2-yl)boronic acid was obtained as a white solid starting from 1.04g of 2-bromonaphtalene following procedures B and D (78%); following procedure A and D with DICAB (yield 80%). 1 B-1-Naphthalenylboronic acid [13922-41-3] 6i 28 10.3 g of (Naphthalen-1-yl)boronic acid was obtained as a white solid starting from 15.52 g of 1-bromonaphtalene following procedures B and D (80%); following procedure A and D with DICAB (yield 82%).…”

“…6r 32 663 mg of B-(3-Chloro-4-methylphenyl)boronic acid was obtained as a white solid starting from 1.03g of 4-bromo-3chlorotoluene following procedures B and D (89%). 1 37 666 mg of B- (3,4-dichlorophenyl)boronic acid was obtained as a white solid starting from 1.13g of 4-bromo-1,2-dichlorobenzene following procedures B and D (88%).…”

“…1 H NMR (300 MHz, acetone-d 6 ): δ (ppm) 7.75-7.72 (dd, J = 3, 6Hz, 2H), 6.80 (s, 2H), 6.72-6.69 (dd, J = 3, 6Hz, 2H), 2.97 (s, 6H). 11 13 C NMR (75 MHz, acetone-d 6 ): δ (ppm) 162.3 (q, J = 247 Hz), 126.32, 124.2, 123.9, 114.2 (q, J = 4.0Hz), 113.9 (q, J = 3.9 Hz) 19 F NMR (282 MHz, DMSO-d6) δ -61.0 4-Biphenylboronic acid [5122-94-1] 6x 32 713 mg of 4-Biphenylboronic acid was obtained as a white solid starting from 1.20 g of 4-bromobiphenyl following procedures B and D (78%). 1 40 prepared from bromobenzene on a 5 mmol scale following procedures A and C (yield 95%) 1 H NMR (300 MHz, acetoned 6 ,) 7.47 (d, J = 6,6 Hz, 2H), 6.99-7.10 (m, 3H).…”