Solid-Phase Diels-Alder Reaction

Solid-phase chemistry is an efficient synthetic tool that, compared with solution-phase chemistry, simplifies the work-up of the reaction, allows the process to be driven to completion by using excess of reagents, and can be automatized [2a]. In recent years, many studies have been devoted to developing both surface-mediated and resin-supported synthesis. Today the solid-phase approach is not limited to peptides and oligonucleotides but is also used to synthesize molecules of lower molecular weight. 

The Diels-Alder reaction on solid support was first performed 20 years ago and is now a consolidated procedure [2b]. 

1 Inorganic Solid-Surface-Promoted Diels-Alder Reaction 

Porous surfaces of inorganic solids such as clays, silica gel, alumina and zeolites are the commonest systems used as catalysts in Diels-Alder reactions. 

Two classes of clays are known [3] (i) cationic clays (or clay minerals) that have negatively charged alumino-silicate layers balanced by small cations in the interlayer space (e.g. K-10 montmorillonite) and (ii) anionic clays which have positively charged brucite-type metal hydroxide layers balanced by anions and water molecules located interstitially (e.g. hydrotalcite, Mg6Al2(0H)16C034H20. 

A compendium of these special methods was reviewed by Pindur in 1993 [1]. 4.1 SOLID-PHASE DIELS-ALDER REACTION 

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A solid-phase Diels-Alder reaction that uses polymer-supported reagents has recently attracted considerable attention and its use is expanding rapidly. 

A polymer-supported silyl triflate and subsequent functionalization synthesis and solid-phase Diels-Alder reactions of silyloxydienes [25]... 

It has to be noted that the temperatures up to 220 °C involved in the transformations on polystyrene-based support do not affect the resin stabihty. The controlled microwave irradiation appeared to be very effective in speeding up the linking of 2(lH)-pyrazinones to an appropriate resin as well as in accelerating the rate of subsequent solid-phase Diels-Alder reaction and the following cleavage of a resulting pyridinone from the sohd support. 

Kaval, N., Van der Eycken, J., Caroen, J.,Dehaen, W.,Strohmeier, G.A., Kappe, C.O. and Van der Eycken, E., An exploratory study on microwave-assisted solid-phase diels-alder reactions of2(lH)-pyrazinones the elaboration of a new tailor-made acid-labile linker, /. Comb. Chem., 2003, 5, 560-568. 

Recent publications about solid phase Diels-Alder reactions (a) B. Nie,... 

SCHEME 16.4. Solid-phase Diels-Alder reaction for the synthesis of 6-epi-dysidiolide. 2002 American Chemical Society. All rights reserved. 

Figure 23 In situ generated side-chain NLO poiymers with or without guest chromophores by solid phase Diels-Alder reaction.

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