Arylboronic acids preparation

Fig. 16.19. Palladium-cata lyzed, stereoselective alkenylation of an arylboronic acid (preparation according to Figure 5.39) with a variety of iodoalkenes. The boronic acid is converted into the boronate anion A. The ion A reacts with the Pd(II) intermediate B via transmetalation subsequent reductive elimination leads to the coupling products.

The SM reaction of sterically hindered arylboronic acids Preparation of 2-(2 -methoxy-46 -di-tert-butylphenyl)-3-methylpyridine (236) [IS)... 

Esterification of arylboronic acids Preparation of phenyl-1,4- diboronic acid bis-pinacol ester (266) 18/... 

Homo-coupling of arylboronic acids Preparation of 2,2 -binaphthyl (166) 122]... 

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

Aryl-5-oxo-1,2,3,5-tetrahydropyrido[ 1,2,3-i/e]quinoxaline-6-carboxy-mides were prepared from 7-chloro derivatives and arylboronic acids in the presence of Na2C03, diphenylphosphinated divinylbenzene-crosslinked polystyrene and Pd(PPh3)4 catalyst. 7-Chloro derivatives were obtained from 7-hydroxy derivatives by heating in POCI3 at 50°C for 3 h (01MIP12). 

This method has been applied to a large-scale preparation of 6-bromoindole, which reacts with various arylboronic acids via the Suzuki reaction to afford 6-aryhndoles fEq. 10.50. 6-Bromo-5-methoxyindole for use in the synthesis of marine bromoindole " and 5-amino-7-ethoxycarbonyhndole for use in synthesis of l//-pyrrolo[3,2-g quina2ohne ring system fEq. 10.51 " have been prepared from the appropriate o-nitrotoluene. 

Arylboronic acids have traditionally been prepared via the addition of an organomagnesium or organolithium intermediate to a trialkyl borate. Subsequent acidic hydrolysis produces the free arylboronic acid. This limits the type of arylboronic acids one can access via this method, as many functional groups are not compatible with the conditions necessary to generate the required organometallic species, or these species may not be stable intermediates. 

Complete characterization of arylboronic acids is often difficult because they are readily transformed into stable cyclic anhydrides called boroxines5 and other polymeric species. Arylboronic acids are also known to be hygroscopic. Thus, arylboronic acids are often prepared and used directly as a mixture of different entities. Commercial arylboronic acids will very often contain varying amount of anhydrides. 

As first described by Krizan and Martin,6 the in situ trapping protocol, i.e., having the base and electrophile present in solution simultaneously, makes it possible to lithiate substrates that are not applicable in classical ortho-lithiation reactions.7 Later, Caron and Hawkins utilized the compatibility of lithium diisopropylamide and triisopropyl borate to synthesize arylboronic acid derivatives of bulky, electron deficient neopentyl benzoic acid esters.8 As this preparation illustrates, the use of lithium tetramethylpiperidide instead of lithium diisopropylamide broadens the scope of the reaction, and makes it possible to functionalize a simple alkyl benzoate.2... 

Salicylideneamino alcohols are easily prepared ligands that react readily with arylboronic acids to form the corresponding esters, which may be monomeric 45-49 or dimeric 50-59 (Fig. 16) [87-94]. 

Ahn, Kim and coworkers, in the preparation of 4-alkylidene-3-arylmethylpyr-rolidines 6/1-77, used a Heck reaction of the vinyl bromide 6/1-76 in the presence of an arylboronic acid [47] (Scheme 6/1.19). ft has been assumed that the interme-... 

Disubstituted furans were synthesized from 1,4-diketones, which were prepared from the reaction of methyl vinyl ketones with arylboronic acids in the presence of CO using rhodium catalyst as illustrated below <06T11740>. 

Trost reported the synthesis of 1,4-dienes with ruthenium catalysis through regioselective carbometallation of alkynes with alkenes.51 Di- and trisubstituted olefins can also be obtained with arylboronic acids through an intermolecular process under rhodium,30 52 55 nickel,56 and palladium catalysis.57 Recently, Larock has reported an efficient palladium-catalyzed route for the preparation of tetrasubstituted olefins.58,59... 

The Suzuki coupling has been utilized to craft (Toctasubstituted tetramesitylporphyrins using various arylboronic acids [62], and Schluter has adopted this reaction to prepare phenyl-pyrrole mixed polymers 75 [63]. The BOC group is easily removed by heating [64] and polymers with molecular weights of up to 23,000 were synthesized. These polymers are potentiaEy interesting for their electrical and nonlinear optical properties [65]. 

In the course of their successful syntheses of the marine alkaloids nortopsentins A-D, Kawasaki and co-workers were able to prepare selectively boronic acid 103 from 1 -(tert-butyldimethylsilyl)-3,6-dibromoindole (102) and effect Suzuki couplings to give 3-arylindoles 104 in good yields [117]. Complementary to this chemistry is the direct Pd-catalyzed reaction of 102 with arylboronic acids to give 6-aryl-3-bromoindoles 105 [117]. 

Martin effected the synthesis of several 3,5-diarylated indoles by a tandem Stille-Suzuki sequence [131]. The latter reaction involves exposure of 3-(3-pyridyl)-5-bromo-l-(4-toluenesulfonyl)indole with arylboronic acids (aryl = 3-thienyl, 2-furyl, phenyl) under typical conditions to give the expected products in 86-98% yield [131], Carrera engaged 6- and 7-bromoindole in Pd-catalyzed couplings with 4-fluoro- and 4-methoxyphenylboronic acids to prepare 6- and 7-(4-fluorophenyl)indole (90% and 74% yield) and 6-(4-methoxyphenyl)indole (73% yield) [29]. Banwell and co-workers employed 7-bromoindole in a Suzuki coupling with 3,4-dioxygenated phenylboronic acids en route to the synthesis of Amaryllidaceae alkaloids [132], Yields of 7-arylated indoles are 93-99%. Moody successfully coupled 4-bromoindole... 

The medicinal importance of 2-aryltryptamines led Chu and co-workers to develop an efficient route to these compounds (130) via a Pd-catalyzed cross-coupling of protected 2-bromotryptamines 128 with arylboronic acids 129 [137]. Several Suzuki conditions were explored and only a partial listing of the arylboronic acids is shown here. In addition, boronic acids derived from naphthalene, isoquinoline, and indole were successfully coupled with 128. The C-2 bromination of the protected tryptamines was conveniently performed using pyridinium hydrobromide perbromide (70-100%). 2-Phenyl-5-(and 7-)azaindoles have been prepared via a Suzuki coupling of the corresponding 2-iodoazaindoles [19]. 

Palladium-catalyzed reactions of arylboronic acids have been utilized to craft precursors for constructing indole rings. Suzuki found that tris(2-ethoxyethenyl)borane (149) and catechol-derived boranes 150 readily couple with o-iodoanilines to yield 151, which easily cyclize to indoles 152 with acid [158]. Kumar and co-workers used this method to prepare 5-(4-pyridinyl)-7-azaindoles from 6-amino-5-iodo-2-methyl-3,4 -bipyridyl [159], A similar scheme with catechol-vinyl sulfide boranes also leads to indoles [160]. A Suzuki protocol has been employed by Sun and co-workers to synthesize a series of 6-aryloxindoles [161]. 

The aryl bromide 40, prepared from cross-coupling between 1,2-dibromobenzene and (trimethylsilyl)acetylene, was converted to the corresponding arylzinc halide 41a and arylboronic acid 41b for subsequent coupling with the haloallenes 42 to produce the benzannulated enyne-allene 43 in -40% yield (Scheme 20.10) [38]. Desilylation with tetrabutylammonium fluoride (TBAF) then afforded 44 in 67% yield. 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

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