Lithium aryl-borate

Lithium-triathyl-hydrido-borat hydroboriert in siedendemTetrahydrofuran aromatisch konjugierte Alkene zu Lithium-tetraalkyl-boraten, die leicht zu Aryl-athanen hydroly-siert werden konnen7. 

In recent years, a variety of aryl boronic acids are commercially available, albeit in some cases they may be expensive for large scale purposes. During our work in the mid-1990 s boronic acid (II) was not commercially available and so two different protocols were used to prepare this acid. The first approach involved the transmetallation with n-butyl lithium of aryl bromide (I) and trapping the lithio species generated with trialkyl borate followed by an acid quench. Aryl bromide (I) is easily prepared by reaction of o-bromobenzenesulfonyl chloride with 2-propanol in the presence of pyridine as a base. The second approach was a directed metallation of isopropyl ester of benzene sulfonic acid (VII), to generate the same lithio species and reaction with trialkyl borate. The sulfonyl ester is prepared by reaction of 2-propanol with benzenesulfonyl chloride. From a long-term strategy the latter approach is... 

An alternative approach to reduce the levels of impurity (VII) would be to have a "transient" existence of the lithio species, so that it reacts instantaneously with trialkyl borate to form the aryl boronate, prior to being quenched by any extraneous proton source to form (VII). Thus, the preparation of boronic acid (II) was improved by changing the order of the reagents. The slow addition of n-butvl lithium also controls the exotherm of the reaction. There was no reaction observed between n-butyl lithium and triisopropyl borate (to form any butyl boronic acid), nor was there any formation of 2-butyl derivative of (VII) formed by reaction between butyl bromide and the lithio species. The reaction is veiy fast and as soon as the addition of n-butyl lithium is completed the reaction is finished. This indicates a rapid transmetallation and instantaneous boronation of the lithio species. The reaction is very much a... 

Ishikura and co-workers have done extensive work on the utility of indolylborates such as lithium triethyl(l-methylindol-2-yl)borate (136), prepared as shown from 1-methylindole, in Suzuki-like Pd-catalyzed reactions [147-157]. For example, 136 couples smoothly with aryl halides to afford 2-arylindoles 137 [147]. The amount of 2-ethyl-1-methylindole by-product, formed by ethyl group migration, can be minimized by refluxing the mixture. At room temperature 2-ethyl-1-methylindole is the major product. More recent work by Ishikura extended these couplings to the (removable) A-Boc analog of 136 with comparable yields to those obtained with 136 [157]. 

Before preparation of any a-halo boronic ester is undertaken, it should be noted that two sets of model conditions are outlined in what follows. If the group R1 of the boronic ester 1 is a typical alkyl group, then the rearrangement of the derived borate complex 2 requires a number of hours at 20 C, but if R1 is aryl or alkenyl, then shorter times and lower temperatures are required in order to avoid epimerization of the product 3 catalyzed by zinc chloride and lithium... 

Lithium alkynyl(trialkoxy)borates have also been found suitable partners for this reaction, and have been success-fully coupled with aryl bromides, iodides, and allyl carbonates. Molander recently reported on the coupling of alkynyltrifluoroborates with aryl bromides, triflates, and chlorides in moderate yields using Pd(dppf)Gl2 as catalyst and GS2GO3 as base, in THF or water at 60... 

Lithium triethyl(l-methylindolyl-2)borate has been introduced as a convenient source of indolyl residue for carbonylative cross-coupling with aryl iodides, alkenyl iodides, or triflates. The reaction requires elevated CO pressure and high loading of catalyst (5mol.%) (Equation (15)). Aryl and alkenyl bromides, as well as aryl iodides... 

Alkynyl(methoxy)borates prepared in situ from an alkynyllithium or sodium and 9-methoxy-9-BBN coupled with 1-alkenyl and aryl halides (Equation (210)).899-902 Addition of triisopropylborate to lithium acetylide yielded an air stable and isolable ate complex that couples with aryl and alkenyl halides (Equation (211)).903 904 Air and moisture stable alkynyltrifluoroborates were probably the most convenient reagents that allow handling in air and coupling reactions in basic aqueous media (Equation (212)).46... 

The synthesis of alkyl-, aryl-, and 1-alkenylboronic acids or their esters from Grignard or lithium reagents and trialkylborates is a classical and efficient method for making relatively simple boron compounds in large quantities (Scheme 2-6) [25]. The stereocontrolled synthesis of alkenylboronic acids and esters involves the reaction of a (Z)- or ( )-2-buten-2-ylmagnesium bromide with trimethyl borate [26]. 

Alternatively, a similar borate intermediate can be obtained by the reaction of organoborate with chloromethyl- or (dichloromethyl)lithiums (eq (22) and (23)). When a chiral diol ester reacts w ith (dichloromethyl)lithium, an optically active a-chloroalkylboronate is produced with an excellent enantiomeric excess [34] (eq (23)). The C-Cl bond is then displaced readily w ith alkyl, aryl, or 1-alkenyl nucleophiles with inversion of configuration. The procedure has been extensively used for the preparation of chiral boronates, which have been used in organic syntheses [30]. 

Probably the best modem method for introduction of OF by electrophilic aromatic substitution is lithiation, reaction with a boronate ester, and oxidation.4 These are the same boron compounds that are used in Suzuki coupling (chapter 18) and are made the same way. In this example, selective mono-lithiation by Br/Li exchange on available tribromoanisole 39 (easily prepared by bromination of anisole or phenol) occurs ortho to the MeO group and reaction of aryl-lithium 39 with trimethyl borate gives the boronic ester 40. Peroxyacids such as peracetic acid are usually used for the final oxidation. 

The electronic nature of the coupling partners could be reversed by introducing a boronic acid fragment on the benzonitrile, such as boronic acid 22c, and affecting the coupling with an aryl triflate of pyridinium bromide. Because the aryl boronate could be prepared using the aryl lithium in the presence of triisopropyl borate, this would obviate the need for the expensive pinacol diborane. Reduction of the intermediate pyridine or tetrahydropyridines would provide the desired products (see Scheme 5.8). 

In studies concerned with optimization of the Suzuki cross-coupling of 2-pyridyl nucleophiles, lithium triisopropyl 2-pyridylborates are shown to be the most suitable boron coupling partners (eq 60). The borates are isolated and subjected to coupling with various aryl and hetaryl halides (X = Cl, Br) to give the corresponding azabiaryls. ... 

Usually, boronic acids are synthesized by reaction of an aryl magnesium or aryl lithium compound with a borate ester [6]. However, in the case of 4-bromo-benzonitrile, a metal-organic intermediate would react with the nitrile group. Aryl boronic acids could be also synthesized by palladium-catalyzed reaction using diboron reagents [7]. This method would certainly tolerate the cyano func-tionahty, but the diboron reagents are very expensive. 

A method of stilbene synthesis via homocoupling of aryl aldehyde tosyDiydrazones in the presence of lithium fert-butoxide and trimethyl borate under reflux in THF has been described. 

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