Boronic acids, metal catalyzed

The Suzuki-Miyaura cross-coupling reaction is a standard method for carbon-carbon bond formation between an aryl halide or triflate and a boronic acid derivative, catalyzed by a palladium-metal complex. As with the Mizoroki-Heck reaction, this cross-coupling reaction has been developed in ionic liquids in order to recycle and reuse the catalyst. In 2000, the first cross-coupling of a halide derivative with phenylboronic acid in [bmim] [BF4] was described. As expected, the reaction proceeded much faster with bromobenzene and iodobenzene, whereas almost no biphenyl 91 was obtained using the chloride derivative (Scheme 36). The ionic liquid allowed the reactivity to be increased, with a turnover number between 72 and 78. Furthermore, the catalyst could be reused repeatedly without loss of activity, even when the reaction was performed under air. Cross-coupling with chlorobenzene was later achieved - although with only a moderate yield (42%) - using ultrasound activation. 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

The transition metal catalyzed cross coupling of an organohalide with a boronic acid derivative, the Suzuki-Miyaura coupling, has become one of the most popular ways of preparing biaryls.3 The reaction is very robust and can easily be scaled to provide multigrams of material.4... 

Martin utilized indoleboronic acids in Pd-catalyzed coupling to great effect, and has improved upon the halogen-metal exchange route to indole-3-boronic acids by adopting a mercuration-boronation protocol as illustrated below for the preparation of 96 and 97 [115,116],... 

Qudguiner s group enlisted a combination of directed metalation and a Pd-catalyzed crosscoupling reaction for the construction of heteroaryl natural products [49]. One example was the total synthesis of bauerine B (64), a -carboline natural product [50], Or/fio-lithiation of 2,3-dichloro-A-pivaloylaminobenzene (61) was followed by reaction with trimethylborate to provide boronic acid 62 after hydrolysis. The Suzuki reaction between 62 and 3-fluoro-4-iodopyridine led to the desired biaryl product 63 contaminated with the primary amine (ca. 30%), both of which were utilized in the total synthesis of bauerine B (64). Another p-carboline natural product, the antibiotic eudistomin T (65), and a few other hydroxy p-carbolines have also been synthesized in the same fashion [3,51]. 

No examples of such reactions have been disclosed. Displacement of halogens on the parent heterocycle through metal-catalyzed processes have surprisingly not been reported to our knowledge on the neutral heterocycle. Recently, Suzuki-Miyaura cross-coupling reactions of imidazolium bromide 113 with various boronic acids or esters were reported <2005T6207> to proceed in good yield, without deprotonation at the C-3 position (Scheme 35). 

Ir(OH)(cod)]2 catalyzed a formal [3+2] cycloaddition of 2-formylphenylboronic acid and 1,3-dienes (Scheme 11.41) [50]. The transmetaUation of boronic acid with iridium would yield aryliridium, where the carbonyl group coordinates to the metal. An electrophihc attack of the diene terminus to formyl carbon would then... 

For the synthesis of a cavitand functionalized with terpyridyl groups via rigid linkages, transition metal catalyzed cross-coupling reactions are especially well suited. Starting with the boronic acid ester 48 [65], attachment of the terpyridyl groups to the cavitand was realized by Suzuki-Miyaura reaction with the tetraiodo-cavitand 47 (Fig. 15). 

The optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

Reactions of organometallic nucleophiles are reviewed mainly under Reactivity of Substituents Metals and Metalloids - this is a change from the Handbook-II policy of considering these under the reactions of Reactivity of Substituents Halides. Transition metal-catalyzed reactions of halides are considered partly under Reactivity of Substituents Halides and partly in the metalloids sections. Transition metal-catalyzed reactions of stannanes, boronic acids, etc., are considered under Reactivity of Substituents Metals and Metalloids. These areas represent the largest proportion of the additional new material since Handbook-II and are certainly the most important. 

In consideration of conceivable strategies for the more direct construction of these derivatives, nitriles can be regarded as simple starting materials with which the 3+2 cycloaddition of acylcarbenes would, in a formal sense, provide the desired oxazoles. Oxazoles, in fact, have previously been obtained by the reaction of diazocarbonyl compounds with nitriles through the use of boron trifluoride etherate as a Lewis acid promoter. Other methods for attaining oxazoles involve thermal, photochemical, or metal-catalyzed conditions.12 Several recent studies have indicated that many types of rhodium-catalyzed reactions of diazocarbonyl compounds proceed via formation of electrophilic rhodium carbene complexes as key intermediates rather than free carbenes or other types of reactive intermediates.13 If this postulate holds for the reactions described here, then the mechanism outlined in Scheme 2 may be proposed, in which the carbene complex 3 and the adduct 4 are formed as intermediates.14... 

Metal-catalyzed Routes to Alpha-Heteroatom-substituted Boronic Acids and Boronate Esters... 

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