Stannylpyrrole

Mono- or bis-bromine-lithium exchange on dibromopyrrole 77 affords stannylpyrroles 78 or 79, respectively, and N-BOC-2-trimethylstannylpyrrole is obtained in 75% yield from N-BOC pyrrole by lithiation with LTMP and quenching with Me3SnCl [15]. 

Although the stannylated pyrroles are normally obtained via lithiation, two other methods to prepare these Stille precursors have been devised. Caddick has found that the addition of tri-n-butylstannyl radical to pyrrole 82 affords stannylpyrrole 83 in good yield [68],... 

The second alternative synthesis of stannylpyrroles involves the versatile van Leusen pyrrole ring synthesis, illustrated below for the synthesis of 85 [69,70]. Several examples were prepared in these studies, although at present the scope of this reaction is limited to pyrroles having an electron-withdrawing group at the 3-position. The structure of a BOC derivative of 85 (Ri = Ph, R2 = Bz) was established by X-ray crystallography [69]. 

Dubac has employed a Stille coupling reaction to synthesize the pyrroles 88 and 89 from stannylpyrrole aldehyde 87 [71]. The latter tin compound was prepared as shown, and related stannylpyrroles were synthesized similarly [72] or using Muchowski s 6-dimethylamino-l-azafulvene dimer lithiation methodology [73]. 

The related stannylpyrrole 90, which was reported by Dubac [72], has been used to synthesize the sponge metabolite mycalazol 11 (91) and related compounds, which have activity against the P388 murine leukemia cell line [74]. 

Stille couplings between stannylpyrrole 92 and siloles 93 and 94 have afforded the silole-pyrrole 95 [75]. These workers also prepared dimers and trimers of 95. 

Pyrrole,110 imidazoles, and 1,2,4-triazoles 111 are readily stannylated on nitrogen, but the products are better considered as stannylamines (Section 16.1) rather than heteroaromatic derivatives. The only route as yet to C-stannylpyrroles with an unblocked NH group appears to be by cycloaddition (see above). 

If the alkyne carries an electron-attracting group, acidolysis of an alkoxystannane84 or of an aminostannane will occur at low temperature,85 86 and (V-stannylpyrroles have been recommended for this purpose because of the non-nucleophilic character of the amine which is liberated.87... 

The bis-stannylpyrrole 134 is obtained irom l-methylpyrrole via 2,5-dibthiation. Subsequent Stille coupling affords 135, which was used to craft novel diguanidine antifungal agents [87]. 

A Stille coupling between stannylpyrrole 136 and 3-bromoindole 137 gave the expected 138 albeit in low yield [63]. Pyrrole 136 was prepared from 80 in the usual manner (1. n-BuLi 2. Bu,SnCl 65%). 

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