Diversity Oriented Synthesis applications

Currently, these reactions are typically conducted with Rh(l) or Ir catalysts. The Pauson-Khand-type reaction of allenynes has also witnessed important developments, especially in its applications to natural products synthesis.388 Brummond s group has been very productive in both areas. Duality in the reaction of allenynes is shown below. In the context of diversity-oriented synthesis, simply changing the reaction conditions gives versatile heterocycles in high yields (Scheme 116).389... 

The perfluoroacetamide catalysts, rhodium(II) trifluoroacetamidate [Rh2(tfm)4] and rhodium(II) perfluorobutyramidate [Rh2(pfbm)4], are interesting hybrid molecules that combine the features of the amidate and perfluorinated ligands. In early studies, these catalysts were shown to prefer insertion over cycloaddition [30]. They also demonstrated a preference for oxindole formation via aromatic C-H insertion [31], even over other potential reactions [86]. In still another example, rhodium(II) perfluorobutyramidate showed a preference for aromatic C-H insertion over pyridinium ylide formation, in the synthesis of an indole nucleus [32]. Despite this demonstrated propensity for aromatic insertion, the perfluorobutyramidate was shown to be an efficient catalyst for the generation of isomtinchnones [33]. The chemoselectivity of this catalyst was further demonstrated in the cycloaddition with ethyl vinyl ethers [87] and its application to diversity-oriented synthesis [88]. However, it was demonstrated that while diazo imides do form isomtinchnones under these conditions, the selectivity was completely reversed from that observed with rhodium(II) acetate [89, 90]. 

Gerencser J, Dorman G, Darvas F (2006) Meldrum s acid in multicomponent reactions applications to combinatorial and diversity-oriented synthesis. QSAR Comb Sci 25 439 48... 

Multicomponent reactions (MCRs) are one-pot processes combining three or more substrates simultaneously [1], MCR processes are of great interest, not only because of their atom economy but also for their application in diversity-oriented synthesis and in preparing libraries for the screening of functional molecules. Catalytic asymmetric multicomponent processes are particularly valuable but demanding and only a few examples have been realized so far. Here we provide an overview of this exciting and rapidly growing area. 

Metathesis is inherently flexible. As a result, this transformation allows, inter alia, for a rapid chemistry-driven evaluation of structure/activity profiles and qualifies for applications in combinatorial and diversity oriented synthesis this is particularly true when combined with suitable post-metathesis transformations exploiting diverse alkene reactivity. 

Muller TJJ (2007) Diversity-oriented synthesis of chromophores by combinatorial strategies and multi-component reactions. In Muller TJJ, Bunz UHF (eds) Functional organic materials. Syntheses, strategies, and applications. Wiley-VCH GmbH KGaA, Weinheim, pp 179-223... 

Natural products are generally complex chemical structures, whether they are cyclic peptides like cyclosporin A, or complex diterpenes like paclitaxel. Inspection of the structures that are discussed in Section IV is usually enough to convince any skeptic that few of them would have been discovered without application of natural products chemistry. Recognition and appreciation of the value of natural product-like models in improving efficiency in so-called diversity-oriented synthesis has already been mentioned. ... 

In this chapter, we address two complimentary approaches to componnd collection development namely, Diversity Oriented Synthesis (DOS) and Biology Oriented Synthesis (BIOS). For additional, very well-validated approaches snch as fragment-based design and the application of in silico methods to develop compound libraries the reader is referred to different chapters in this book and to authoritative reviews. " ... 

Marcaurelle, L. A. and Johannes, C. W. 2008. Application of natural product-inspired diversity-oriented synthesis to drug discovery. Prog. Drug Res. 66 187,189-216. 

Scheme 12.5 Schreiber and coworkers application of substituted [3]dendralenes in diversity-oriented synthesis.

For another application of such a tandem strategy, RCM together with Ugi 4CR was utilized in a diversity-oriented synthesis (DOS) approach suitable for small to medium ring sizes. ° The 4CR constructs the basic framework of the structure, which, through a variety of additional transformations, can be converted to 12- to 16-membered macrocycles (for example 191, Scheme 11.25, building block contributions to the molecule and RCM site and catalyst indicated). 

The functional group tolerance of the ruthenium-based metathesis catalysts has had a tremendous impact on solid-phase organic synthesis. The efficacy of the reaction in solution generally translates directly to solid-phase transformation and its potential has been harnessed in a number of library syntheses, solid-phase syntheses of natural products, or diversity-oriented syntheses. It enables the use of chemically robust alkenes as linkers which can be cleaved by RCM or CM. It, of course, provides new manifolds of diversification in diversity-oriented synthesis as has been elegantly shown in landmark examples by Schreiber and Nelson. Another metathesis application of paramount importance is in peptide chemistry where solid-phase synthesis is omnipresent. The ability to stabilize secondary structures in short peptide motifs and replace pharmacologically unsuitable disulfide bonds or simply restrict the conformation of a peptidic library has already been successfully implemented in a number of important examples. The orthogonality of the metathesis reaction to peptide chemistry provides a really powerful tool in this regard. 

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