Pyrrole-3-boronic acid

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. 

Fig.7 Structures of a tetrakis(p-aminophenyl)porphyrin, b pyrrole-3-boronic acid and c 1-methyl-3 (1-pyrrole-l-ylmethyl)pyridinium tetrafluorob orate...

Swager has utilized pyrrole-3-boronic acid 102, which was prepared from 6 by NBS bromination (88%), lithiation (BuLi), and boronation (B(OMe), aq MeOH) (50% overall), in Suzuki reactions to synthesize bis-pyrroles 104-106, en route to novel conductive electrochromic polymers [73]. 

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... 

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... 

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 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]. 

Milkiewicz and coworkers [16] prepared a series of novel tetra-substituted furo[3,2-b Ipyrroles from the methyl or ethyl 3-bromo-2-phcnyllliro 3,2-/ pyrrole-5-carboxylate 40, which was prepared from 3-bromo-2-phenylfuran-2-carbaldehyde 39. The compounds 40 were subjected to a Suzuki coupling with 4-chlorophenyl boronic acid to form 41, which was treated with a variety of alkylating agents to afford the corresponding esters 42. The esters were then saponified to acids 43 (Scheme 6). 

However, studies on the scope of this sequence revealed that the substrate has to be an N-tosyl sulfonamide and that certain boronic acids are not trans-metallated but rather give rise to the formation of the pyrrole 21 or a pyridine derivative 22 (Scheme 7). The peculiar outcome as a carbopalladation-Suzuki sequence is rationalized by co or dinative stabilization of the insertion intermediate 18 by the sulfonyl oxygen atom, as represented in structure 19, now suppressing the usual /3-hydride elimination. If the transmetallation is rapid the Suzuki pathway is entered leading to product 17. However, if the transmetallation is slow, as for furyl or ferrocenyl boronic acid, either /i-hydride elimination or a subsequent cyclic carbopalladation occurs. The former leads to the formation of the diene 20 that is isomerized to the pyrrole 21. The latter furnishes the cyclopropylmethyl Pd species 23, which rearranges with concomitant ring expansion to furnish piperidyl-Pd intermediate 24 that suffers a -hydride elimination to give the methylene tetrahydro pyridine 22. 

Facile synthesis of simple 3-arylpyrroles from pyrroline by tandem Suzuki dehydrogenation reaction is depicted in Scheme 229. Thus, treatment of l-benzyl-2,5-dihydro-l//-pyrrol-3-yl trifluoromethanesulfonate 1195 (prepared in 55% yield from l-benzyl-3-pyrrolidinone 1194 by trapping the enolate with a triflating reagent), with boronic acid derivatives leads to the formation of 3-arylpyrroles 1196 in good yields (65-74%) <2000TL3423>. 

The Suzuki cross-coupling reaction between 1,2,5-trisubstituted pyrrole halides 1443 and 2-A -(/-butoxycarbonyl)-aminophenyl boronic acid 1444 performed with benzyl[bis(triphenylphosphine)]palladium(ll) chloride (PdBnCl(PPh3)2)... 

The unsubstituted pyrrole-2-boronic acid 93 was coupled with pyridyl bromide 94 on a Wang resin to afford nicotinic acid derivative 95 after cleavage [69]. 

Various aromatic rings show good selectivities without requiring directing groups and a range of substituted boronic acids are tolerated. Electron rich heterocycles such as indole and pyrrole are readily employed in the coupling reaction and selectivity appears to be controlled by the electronic properties of the arenes. 

Two biphenyl-derived phosphines (shown below) are proposed as effective ligands for general heterocyclic Suzuki couplings, covering a wide range of ring systems, both as boronic acids and/or the halide component. Examples include thiophene-2- and -3-boronates, pyrrole-2- and -3-boronates, furan-2-boronates, indole-5-boronates and pyridine-3- and -4-boronates. 

Lithiation of A-protected indoles is the main route to 2-boronic acids, which have found wide use, although the usual protecting groups (Boc and arylsulfonyl) increase the ease of deboronation. With Boc-protected derivatives, the indole is less consistent than the pyrrole in coupling reactions. In situ protection of the indole NH as the A-carboxylate can be used to prepare both the 2-boronic acid and 2-tri-n-butylstan-nane for one-pot coupling procedures. 

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. ... 

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