Combinatorial chemistry intramolecular reaction

Most of the examples in this chapter deal with one (intramolecular reactions) or two components. With the advent of combinatorial chemistry, multicomponent reactions stitching together three or more building blocks have emerged as potent tools. 

Dipolar cycloaddition reactions are of main interest in nitrile oxide chemistry. Recently, reviews and chapters in monographs appeared, which are devoted to individual aspects of these reactions. First of all, problems of asymmetric reactions of nitrile oxides (130, 131), including particular aspects, such as asymmetric metal-catalyzed 1,3-dipolar cycloaddition reactions (132, 133), development of new asymmetric reactions utilizing tartaric acid esters as chiral auxiliaries (134), and stereoselective intramolecular 1,3-dipolar cycloadditions (135) should be mentioned. Other problems considered are polymer-supported 1,3-dipolar cycloaddition reactions, important, in particular, for combinatorial chemistry... 

The Pauson-Khand reaction [329, 330, 331, 332] has been applied in combinatorial chemistry for some years [333, 334, 335]. Its mild reaction conditions have allowed application in SPOS. In this Co2(CO)8-mediated reaction, an alkyne, an alkene, and a CO molecule initially bound to the Co reagent react to form cyclopentenone. If alkene and alkyne are tethered, tricyclic structures can be obtained. Thus, Ku-boto et al. reported the intramolecular Pauson-Khand reaction of DES-bound 2-3 di-dioxy 2,3-unsaturated propargyl glucoside (413). The latter were accessible from glucal via a Perrier reaction. The alkene and ketone moieties of the reaction products allowed further diversification (Scheme 83) [336]. 

A novel methodology employing aza-Payne rearrangement and OJ<[-intramolecular acyl transfer reactions was reported by Tamamura et for the synthesis of peptidomimetics containing hydroxyethylamine dipeptide isosteres (87). This method is also applicable for the synthesis of hydroxyethylamine dipeptide isosteres containing pseudopeptides and also for combinatorial chemistry using solid-phase techniques. 

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