5-indole boronic acid

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],... 

Alkenylzirconium compounds 34 obtained by the hydrometallation of alkynes were transformed to 1-alkenylboron compounds via transmetallation with B-halo-9-BBN or B-chlorocatecholborane62,63 (Scheme 5). Mercuration followed by transmetallation to BH3 was advantageous over the lithiation route in the synthesis of indole-3-boronic acid 35.64... 

In addition to the very important palladium-catalysed reactions, boronic acids undergo a number of useful reactions that do not require transition-metal catalysis, particularly those involving electrophilic ipso-substitutions by carbon electrophiles. The Petasis reaction involves ip,y(9-replacement of boron under Mannich-like conditions and is successful with electron-rich heterocyclic boronic acids. A variety of quinolines and isoquinolines, activated by ethyl pyrocarbonate, have been used as the Mannich reagent . A Petasis reaction on indole 3-boronic acids under standard conditions was an efficient route to very high de a-indolylglycines. " ... 

TBS and 1-TIPS indole-3-boronic acids, prepared in situ via halogen exchange, conple weU with a range of heterocyclic snbstrates. ... 

The Suzuki method for cross-coupling involves use of an arylboronic acid as the nucleophilic component. These conditions have been successfully applied to indoles. Indole-3-boronic acids, which can be prepared via electrophilic mercuration, can be coupled with vinyl triflates (Scheme 130) <93TL2235>. 

The synthesis of dictyodendrins A and F was realized through a sequential C—H functionahzation strategy inclusive of an initial C3 arylation, a site-selective double C—H alkylation with an aryldiazoacetate derivative and a subsequent Suzuki-Miyaura cross-coupHng with indole-3-boronic acid pinacol ester 107 (2015JAC644). A formal 67r-electrocyc-lization of the resultant tetrasubstituted pyrrole 108 fashioned the required pyrrolo-[2,3-c]carbazole core (109) which was further elaborated to the targets. 

Furstner has also used his methodology [58] as presented in Scheme 24 for the preparation of lycogalic acid dimethyl ester (135) and this is presented in Scheme 27. The ability to access indole boronic acids is an important consideration for this particular route. 

Chloropyrazine (115, R = Cl) gave 5-(pyrazin-2-yl)indole (117) [5-indole-boronic acid, Pd(PPh3)4 NaHC03, MeOCH2CH2OMe—H20, N2, reflux, 4 h 55%].326... 

D Boronic acid coupling 10 l-(4-Methylphenylsulfonyl)indole- l-Benzyl-3-trifluoromethanesulfonyloxy-l,2,5,6- 92 [10]... 

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). 

Cossy and coworkers described a precise combination of a Heck and a Suzuki-Miyama reaction using ynamides and boronic acids to give indole and 7-azaindole derivatives [46]. Thus, reaction of 6/1-73 with 6/1-74 using Pd(OAc)2 as catalyst led to 6/1-75 in 68% yield (Scheme 6/1.18). 

Watanabe reports a new method for the direct conversion of o-choroacetaldehyde N,N-disubstituted hydrazones into 1-aminoindole derivatives 93 by palladium-catalyzed intramolecular ring closure of 92 in the presence of P Bu3 or the bisferrocenyl ligand 94 <00AG(E)2501>. When X = Cl, this cyclizative process can be coupled with other Pd-catalyzed processes with nucleophilic reagents (e.g., amines, azoles, aryl boronic acids) so as to furnish indole derivatives with substituents on the carbocyclic ring. 

An alternative method of producing indole-containing compounds involves a bis-Suzuki reaction of 2,3-dihaloindoles 114 with 2 equiv of boronic acids 115 with 10 mol % Pd(OAc)2 [75]. The paper describes the difference in electronic effects of the boronic acids. Electron-rich boronic acids give better yields (85-95%) whilst the electron-deficient boronic acids give poorer yields (44-55%). Scheme 28 shows the general synthesis of these compounds. 

Boronic acids 96 and 97 couple very well with vinyl triflates 98 and 99 under typical Suzuki conditions (Pd(PPh3)4/Na2C03/LiCl/DME) to give indoles 100 and 101, respectively, in 76-92% yield [115, 116]. Enol triflates 98 and 99 were prepared in good yield (73-86%) from N-substituted 3-piperidones, wherein the direction of enolization (LDA/THF/-78 °C PhNTf2) is dictated by the tf-substituent. 

Snieckus described short syntheses of ungerimine (121) and hippadine by Suzuki couplings of boronic acid 118 with 7-bromo-5-(methylsulfonyloxy)indoline (116) and 7-iodoindoline (117), respectively [130]. Cyclization and aerial oxidation also occur. Treatment of 119 with Red-Al gave ungerimine (121) in 54% yield, and oxidation of 120 with DDQ afforded hippadine in 90% yield. Indoline 116 was readily synthesized from 5-hydroxyindole in 65% overall yield by mesylation, reduction of the indole double bond, and bromination. Indoline 117 was prepared in 67% yield from N-acetylindoline by thallation-iodination and basic hydrolysis. 

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]. 

Adapting Gribble s method for synthesizing indol-3-yl triflate [37], Mdrour et al converted 2-formyl- l-(phenylsulfonyl)- l//-indole (31) to indol-2-yl triflate 32 in two steps. 32 was subsequently coupled with benzofuryl-2-boronic acid to furnish 2-benzofurylindole 33 [38, 39]. In another case, 2-bromoacetaniline was coupled with 2-formyl-3-furylboronic acid 35 [40]. The resulting Suzuki coupling adduct underwent a spontaneous cyclization, forming tricyclic furo[2,3-c]quinoline 36. 

Vilsmeier reaction of 2-oxindole (830) afforded 2-chloroindole-3-carbaldehyde (891). Suzuki cross-coupling of 891 with furan-3-boronic acid (1124), followed by protection of the indole nitrogen with benzyloxymethyl (BOM) chloride, led to... 

One of the starting materials, the bromoindolinemesylate 183 was obtained from the commercially available 5-hydroxyindole by mesylation followed by successive treatment of the resulting indole derivative with sodium cyanoborohydride and bromine. Coupling of 183 with the known boronic acid 184 in the presence of zero valent palladium complex led directly to the lactam 185, the intermediate carbinolamine 186 formed initially in the reaction suffering facile aerial oxidation during work-up. On reduction with sodium (2-methoxyethoxy)aluminium-hydride, the amide 185 yielded the aminophenol 187 which on chromatography underwent oxidative aromatisation to 182 in 54% yield. 

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