Pyrazole-5-boronic acid

Pyrazole could also be protected as its corresponding tetrahydropyranyl (THP) derivative by treating pyrazole with 3,4-dihydro-2//-pyran (DHP) with the aid of a catalytic amount of TFA. " C5-Lithiation of THP-pyrazole could also be achieved using n-BuLi. Pyrazole-5-boronic acid was prepared in this fashion. 

Pyrazole-based COX-inhibitors were synthesized using Pd/C as a heterogeneous and ready-filterable palladium source. Electron-deficient boronic acids coupled well while orf/zo-substitulcd and electron-rich boronic acid were less reactive (Scheme 62) [146]. The same team also developed a two-step and one-pot procedure for the synthesis of styrene-based nicotinic acetylcholine receptor antagonists. 

Straightforward 5-lithiation results using -BuLi with ethyl 3-mcthoxy-l -methyl-17/-pyrazol-4-earboxy late and halides, zincates, or boronic acids can thus be produced <2002SL769>. A neat device allows 3-lithiation of indazole silylation at N(2) allows the desired 3-metallation (Scheme 60) <2006EJ02417>. 

A different route employs organoborohydrides RBH2 or LiRBH3,31 obtained from the reaction of the corresponding boronic acids RB(OH)2 with LiAlH4,32 in the reaction with pyrazolate ion and excess pyrazole (Equation (3)).33... 

This conversion employs a boronic acid with a copper(ll) catalyst. The method was developed for reactions of heterocycles, including the V-arylation of isatin ° and of pyrazole, imidazole and their benzo derivatives (1,2,3-triazole, 1,2,4-triazole and 5-phenyltetrazole gave only very modest yields). These conditions also apply to the V-arylation of 2-pyridone (and various fused derivatives), 3-pyridazinones, indole-2-carboxylates and pyrrole-2-carboxylates. ... 

In 1999 Combs and colleagues published a procedure for N-arylation of imidazoles, pyrazole, and 1,2,3-triazole attached to a solid support [124]. Interestingly, they used p-tolyl boronic acid as the arylating agent when employing Cu(II) cataly-... 

The tide compounds are obtained in moderate to good yields. While the 3- and 5-biphenyl-substituted derivatives 24 and 25 can be synthesized by applying the same reaction conditions, the synthesis of 1-biphenylsubsti-tuted pyrazoles 26 requires a different set of conditions, most notably dichloromethane as solvent instead of tetrahydrofuran (THF). The 3-biphe-nylsubstituted pyrazoles 25 are generally obtained in the h hest overall yields. In terms of the appHed boronic acid 22, electron-donating, electroneutral, and electron-withdrawing substituents are accepted. 

A general method for solid phase synthesis ofN-arylated benzimidazoles, imidazoles, triazoles and pyrazoles has been demonstrated utilizing copper (II) mediated coupling of aryl boronic acids under MWI (Scheme 71). ... 

Ihara and Suginome in 2009 reported the o-silylation of certain 2-pyrazol-5-ylaniline boronic acid derivatives using RuHjjCOjlPPhjjj [119]. 

The reactivity of the closely related system TpMe2PtMeH2 toward electrophiles in arene solvents has also been reported recently (68). The boron-based Lewis acid B(C6F5)3 induced elimination of methane and formation of an aryl(dihydrido) platinum(IV) complex via arene C-H activation (Scheme 17, A -> C). The active acid may be either B(C6F5)3 or alternatively a proton generated from B(C6F5)3 and trace water. It was proposed that the acid coordinates to a pyrazole nitrogen (shown in Scheme 17, B) forming an intermediate five-coordinate platinum(IV) complex, which readily eliminates methane. 

Pyrazole derivatives in which a boron is bonded directly to a pyrazole-carbon atom are exceedingly scarce. Only three such compounds have been described in the literature all of which were obtained by cycloaddition reactions. For example, (n-C HgO)2BC=CH was found to react with ethyl diazoacetate to yield the ester / as the initial product, but which was isolated as the corresponding dihydroxyborane. The latter has been hydrolyzed to yield the acid 2. 

Subsequently, several additional monomeric pyrazol-l-ylboranes containing trigonal boron have been described. They are, however, all species in which the boron is incorporated into a 1,3,2-diazaboracycloalkane ring as shown in 5. This feature is believed to provide for a sufficient electronic saturation of the boron by annular 7i-backbonding from the two adjacent nitrogen atoms to reduce the Lewis acidity of the boron and thus prevent dimerization to a pyrazabole. The known species of type 5 are surveyed in Table 1. 

Although the known monomeric pyrazol-l-ylboranes of type 5 do not dimerize with the formation of pyrazaboles, their boron atom has residual Lewis acidity. Hence, they have been found to form 1 1 molar complexes with various nitrogen ba s (see Sect. IIl.B). In addition, an unusual dimerization has been observed for l,3-dimethyl-2-(l-pyrazolyl)-l,3,2-diazaboracyclopentane (compound Nr. 1 in Table 1) at low temperatures On the basis of NMR data, structure 6 was assigned to this dimer... 

The nitrogen extrusion from 1-pyrazolines and 3H-pyrazoles giving cyclopropanes and cyclopropenes, respectively, has been extensively reviewed The cyclopropane synthesis from 1-pyrazolines can be executed thermally as well as photochemically, but the latter method generally gives substantially better results than the former. The major side reaction observed in the thermal process is the production of olefins, which arise in the migration of a substituent from the C(4) to C(3) position. A retro-1,3-dipolar addition producing a diazoalkane and an olefin has been observed in certain cases. The decomposition of 3-acyl- or 3-alkoxycarbonyl-1-pyrazolines is catalyzed by acids, such as perchloric acid and boron trifluoride and by Ce The stereochemical course... 

Boron halides, hydrides, arylboronic acids and corresponding esters can be employed as boron sources, when specific R on the boron atoms are requested. For example, the boron-substituted RTpx (RB(pzx)3) may be synthesized according to the following reaction (1.1) by using pyrazolate ion and excess pyrazole ... 

Furthermore, pyrazol-3-ones have been oxidized by a variety of oxidizing agents such as ozone in oxygen, hydrogen peroxide solution, 3-chloroperbenzoic acid, aqueous sodium periodate, lead(IV) acetate with boron trifluoride etherate, or atmospheric oxidation. The reactions lead mainly to epoxidation of an alkene or imine functionality and cleavage of the pyrazol-3-one ring. 

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