Templated-assisted coupling

Figure 8.1 Two different pathways for aniline enzymatic polymerization. On top, traditional ortho-coupling. Below, template-assisted enzymatic polymerization of aniline. (Reproduced with permission from [15]. Copyright (1998) American Chemical Society).

In generalizing the latter examples one may be tempted to assume that all metal-assisted cyclization and cross coupling reactions are templated processes. This viewpoint, however, not only sets an impractically wide scope for a review, it may even be incorrect. Therefore, the present article does not try to cover all potentially templated ring closure reactions [4], but presents just a very limited and personal selection of metal-assisted or metal-catalyzed cyclizations based on C-C coupling reactions. They are analyzed with the intention to deduce more accurately what the phenomenological effect of tern-plating refers to. 

The random biosynthesis process is imder review. Dirigent proteins, acting as templates, are proposed to assist the orientation of hgnin precursors to afford stereoselective phenoxy radical coupling (2,3). 

In an analogous (but slightly altered) manner, the synthesis of 60 (Scheme 4.14) started with l,5-dibromo-2,4-diiodobenzene 57 [76] as a C2v-symmetric template. Reaction with TMSA and deprotection gave l,5-dibromo-2,4-diethynylbenzene. Another Sonogashira coupling, this time with l-bromo-2-iodobenzene, provided the tetrabrominated 58. This material underwent a four-fold exchange of bromides with TMSA and, after fluoride-assisted deprotection, yielded hexayne 59. The cyclization to 60 proceeded smoothly under the conditions of [CpCo(eth)2] catalysis (see Experimental Section). 

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