Prospect of metal-catalyzed C-C forming cross-coupling reactions in modern solid-phase organic synthesis
Prospect of metal-catalyzed C-C forming cross-coupling reactions in modern solid-phase organic synthesis
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DOI：
10.1021/cc800020b
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发表时间：
2008-07-01
影响因子：
--
通讯作者：
Mata, Ernesto G.
中科院分区：
文献类型：
--
作者：
Testero, Sebastian A.;Mata, Ernesto G.
Solid-phase organic synthesis (SPOS) has evolved in the past few years to become a widely used tool for the preparation of a large number of structurally diverse compounds for combinatorial libraries. The generation of molecular diversity by solid-phase methodologies was originally focused on the synthesis of the peptide and oligonucleotide libraries. 1 However, after the pioneering work by Ellman2 in the solid-phase synthesis of benzodiazepines, the scope of polymer-supported chemistry was expanded beyond the preparation of those biopolymers to reach the synthetically more complicated, drug-like, small organic molecules. In recent years, an increasing interest from both academia and industry has motivated the adaptation to solid support of many procedures that were originally developed for liquid phase. As a result, multiple parallel syntheses in a combinatorial way have emerged as indispensable tools to speed up drug discovery in modern life science. SPOS offers some advantages as compared to solution chemistry. Purification is facilitated by simple filtration, avoiding time-consuming separation techniques; consequently, building blocks and reagents can be added in excess to drive reactions to completion. Amenability to automate and the less favorable interference between functionalities linked to the solid support are other benefits of this chemistry. A result of the latter is the “pseudo-dilution effect” 3 that makes intramolecular macrocyclization a suitable reaction that could be carried out efficiently on solid-phase rather than in solution. Last, but not least, solidphase techniques allow the use of high-boiling solvents because their evaporation is not an issue. In this context, because of their central role in modern organic synthesis, catalytic coupling reactions were a logical target of the development of solid-phase synthesis from the very beginning of this methodology. 4 Therefore, this type of reaction was soon established as a widespread tool for solid-phase synthesis, particularly, for carbon-carbon bond formation. For instance, solid-phase variants of the Stille, Heck, Suzuki, and Sonogashira couplings are now well recognized reactions. Despite this unquestionable development, the research in the area is far to be completed. Sometimes, the success of a reaction depends on the kind of support or linker used. On the other hand, new catalytic couplings and new versions of known catalytic couplings appear in the literature almost every month; new and more efficient catalysts are also frequently reported giving the opportunity to improve low-yielding procedures. A quick overview of the state-of-the-art in metal-catalyzed carbon-carbon-forming reactions on solid support can help us to establish some guidelines for their future development. Because our emphasis will be on cross-coupling reactions, some excellent reviews can be consulted for a more comprehensive view of organometallic chemistry on solid phase. 5
