Library furans

The isorniinchnone cyclization/isocyanate cycloreversion process for substituted furan synthesis has been well studied, as exemplified by the conversion of 104 to 106 (Scheme 19.19). In a solid-phase adaptation of this transformation, two groups independently utilized this reaction to estabhsh a traceless self-cleaving method for the synthesis of substituted furans [176, 177]. Further investigation of the thermal requirements of this cycloreversion led to its application in the split-pool synthesis of a small library of amides [178]. 

The Paal-Knorr synthesis of furans as well as thiophenes and pyrroles has been carried out on solid support and a library of heterocyclic compounds has been prepared <2003SL711>. It has been shown that the acid-catalyzed synthesis of 2,3>4-substituted furans from 1,4-diketones can be assisted by microwave irradiation <20040L389>. 

The attachment of a,fi-unsaturated carbonyl compounds to polymeric supports via silyl-enol ether has been employed in some combinatorial libraries. Thus, a,(3-unsaturated lactones (316, 321) can be enolized by KHMDS, then trapped by polystyrene-bound silylchlorides (315) [311]. The resulting furans (317, 322) reacted with methylacrylate to give only endo adducts (319, 323) (Scheme 67). 

Keay <96SL135> has used an intramolecular furan [4+2] adduct to approach the C15-C23 segment of the vebturicidins. These types of reactions are also finding use in the synthesis of medicinal agents and diverse libraries for drug discovery (Scheme 33). 

The power of furan has long been appreciated in target-oriented synthesis and more recently in diversity-oriented synthesis. Schreiber has made elegant use of the embedded diversity in this heterocycle to build complex, natural product-like libraries <03SCI1613 04JA14095> (Scheme... 

A library of resin bound furans 294-296 with diverse appendages were prepared and oxidized. Those furans with appended diols gave bicyclic acetals 297, those with a single alcohols the hydropyrones 298 that underwent dehydration and those without a hydroxyl gave the open-chain compounds, thus generating three structural types from a common intermediate. This last diversity-oreiented example nicely illustrates the synthetic flexibility and power offered by the use of furans. It is certain that the role of furan in complex-molecule synthesis will continue to expand in many new directions. 

A conformationally restricted 2,3-diarylbenzo[i)]furan library was built up on solid-phase by the palladium/bipyridy-catalyzed annulation of o-alkynyl phenols with aryl halides <04JOC2235>. 

To further illustrate the utility of this solid-phase synthesis, a small (32 member) combinatorial library of furans was generated via split synthesis by using the stepwise cycloaddition sequence. From eight carboxylic acids, two malonyl chlorides and two acetylenes, a library of four pools comprising eight compounds each was synthesised. 

The neutral five-coordinate precatalysts [2,6-(ArN=CR)2C5H3N]MX2 (1 M = Fe 2 M = Co X = Cl or Br) can be obtained in high yield by reaction of LI (and also L2-L5) with an anhydrous or hydrated divalent iron or cobalt hahde in tetrahydro-furan or n-butanol (Scheme 5.2) [1-7]. Using this facile synthetic approach an impressive library of examples of 1 and 2 have been developed (for a comprehensive list the reader is referred to a series of recent reviews [13-15]), displaying a range of different symmetries (e.g., C2V, C2, Cs or Ci). It should be noted that if LI lacks sufficient steric bulk (e.g., Ar = Ph), bis(ligand) salts of the type [ 2,6-(ArN= CR)2C5H3N 2M][MX4] (3) can be formed [33, 37]. 

Liao, Y., Reitman, M., Zhang, Y, Fatiii, R. and Yang, Z. (2002) Palladium(II)-mediated cascade carbonylative annnlation of o-alkynyl-phenols on sdyl bnker-based macrobeads a combinatorial synthesis of a 2,3-disubstituted benzo[b]furan library. Organic Letters, 4, 2607-2609. 

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