Pyrrole boronate

As we have seen in Chapter 1, the Suzuki coupling reaction is a powerful method for preparing biaryls and several applications in pyrrole chemistry have been described. Schliiter reported the first pyrrole boronic acid 57, but, surprisingly, the related pyrrole borate 58 could not be hydrolyzed [15]. 

A similar sequence with 5-substituted pyrrole boronic acids 89 affords a range of 2-aryl- and 2-hetarylpyrroles 90 [68]. Boronic acids 89 were prepared as shown for 84. This study included the synthesis of bis-pyrrole 91 from 89 (R=Et) and... 

Similarly, pyrrole boronate 110, which was prepared from 51, coupled regioselectively with bromopyiazine 111 to give 112 (77%), en route to the synthesis of (+)-dragmacidin F [43]. 

Although the synthesis of multiple-pyrrolyl compounds can be achieved by SnAt reactions of perfluoroaromatics with pyrrolylsodium at ambient temperature <96JOC9012>, deleterious side reactions are often observed during attempted A-alkylations of the alkali salts of pyrrole. A protocol has therefore been developed for the preparation of N-arylmethylenepyrroles by reduction of the corresponding AT-acyl derivatives by treatment with sodium borohydride/boron trifluoride etherate in a sealed tube <96S457>. ... 

The drug discovery route to compound 1 started out with the expensive and poorly available boronic acid 2, which was coupled with aryl bromide 3 (Scheme 8.1). Hydrogenation of the resulting pyrrole 4 provided the racemic pyrrolidine 5. At... 

In the area of ion sensing, cation recognition by electrodes containing functionalized redox-active polymers has been an area of considerable interest. Fabre and co-workers have reported the development of a boronate-functionalized polypyrrole as a fluoride anion-responsive electroactive polymer film. The electropolymerizable polypyrrole precursor (11) (Fig. 11) was synthesized by the hydroboration reaction of l-(phenylsulfonyl)-3-vinylpyrrole with diisopinocampheylborane followed by treatment with pinacol and the deprotection of the pyrrole ring.33 The same methodology was utilized for the production of several electropolymerizable aromatic compounds (of pyrrole (12) (Fig. 11), thiophene (13 and 14) (Fig. 11), and aniline) bearing boronic acid and boronate substituents as precursors of fluoride- and/or chloride-responsive conjugated polymer.34... 

The Teixidor team further improved upon this chemistry by covalently linking units of 109 to the polypyrrole monomer prior to electropolymerization.139 A [3,3 -Co(C2B<)H11)2] anion was covalently bound to a pyrrole via a spacer through one of its boron atoms by the reaction of the species [3,3 -Co(8-C4H802-l,2-C2B9H10)(r,2 -(C2B9H11)2] with potassium pyrrole, as functionalization through... 

In this method, Furstner converts N-BOC protected pyrrole to the 2,5-dibromo compound (122) with NBS and this is followed by metalation and carbomethoxylation with t-butyl lithium in THF and subsequent trapping of the metalated species with methyl chloroformate to yield a pyrrole diester (123). Bromination of this diester at positions 3 and 4 with bromine in water followed by Suzuki cross-coupling with 3,4,5-trimethoxyphenyl boronic acid yields the symmetrical tetrasubstituted pyrrole (125). Base-mediated N-alkylation of this pyrrole with 4-methoxyphenethyl bromide produces the key Boger diester (126) and thereby constitutes a relay synthesis of permethyl storniamide A (120). 

Ketcha has prepared l-(phenylsulfonyl)pyrrole-2-boronic acid (65) in low yield and effected Suzuki coupling reactions to afford the corresponding 2-aryl derivatives 66 [58]. 

The pyrrole-3-boronic acid 67 has been prepared from the 3-iodopyrrole by Muchowski and subjected to a range of Suzuki couplings to afford 2-arylpyrroles 68 [59]. Subsequent fluoride deblocking to give 69 occurs in excellent yield. 

The pyrrole component can also be employed as the aryl halide in Suzuki coupling with aryl boronic acids. Thus, Chang has effected several such reactions using phenylboronic acid and halopyrroles such as 70 and 71 [60]. 

In times past it was thought that indoles already bearing an alkyl substituent at C-3 were further alkylated by direct attack at C-2. However, although 2,3-dialkylindoles are readily formed the reaction still involves attack at C-3. This can be demonstrated by the example in Scheme 7.3, where 3-(4 -hydroxybutyl)indole, containing an isotopic label located at C-T, is treated with boron trifluoride in diethyl ether. Two 1,2,3,4-tetrahy-drocarbazoles (l,2,3,4-tetrahydrodibenzo[6,J)pyrroles) are formed in a ratio of 1 1. These differ only in the position of the label. This result indicates that a 3,3-spiroindoleninium intermediate is formed first, and this then undergoes rearrangement of either bond a or bond b to C-2. As the two bonds a and b are identical, equal amounts of the tetrahydrocarbazoles... 

The aminoboranes containing NR2 groups do not form neutral complexes because the B—N bond possesses a higher n order than B—O and B—S bonds. In contrast, the pyrazol-l-yl and pyrrol-l-yl boranes with sp2 nitrogens bonded to the boron do give stable amine complexes... 

A number of patents have appeared on the preparation of biologically active sulfonyl derivatives of 2,3-dihydro-l,2,3-diazaborines. The boron heterocycle is fused to benzene, furan, pyrrole or thiophene e.g. 79GEP2809212). Apparently the compounds have bactericidal as well as fungicidal and trichomonacidal properties. 

The following chemicals were obtained from Aldrich Chemical Company, Inc. and used without further purification 1,3-dimethoxybenzene (99%) butyl lithium (1.6 M in hexanes) 1-formylpiperdine (99%) boron trifiuoride-diethyl ether (purified, redistilled) 2,3-dichloro-5,6-dicyano-l,4-benzo-quinone (98%), and pyridine hydrochloride (98%). All solvents were reagent grade and were obtained from Fisher Scientific and used without further purification except where noted. Silica gel (230-400 mesh) was obtained from EM Scientific. Chloroform was stored over activated, 4-A molecular sieves for at least 24 h prior to use. Tetrahydrofuran (optima grade) was distilled from sodium benzophenone. Pyrrole (99%) was obtained from Aldrich Chemical Company, Inc. and distilled from calcium hydride. 

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