Traceless Concept Based on Cycloaddition-Cycloreversion

A novel concept in traceless solid-phase synfhesis is based on cycloaddition-cyclor-eversion. Cycloadditions are synthetically useful reactions wifh a wide scope for the construction of rigid templates of different ring sizes. Due to fhe potential for variation of fhe substituents on the components for cycloadditions and their versatility, fhis allows an efficient introduction of diversity. 

the reaction of 144 with alkynes yielded polymer-bound intermediates 145. The release of the final products was performed in two steps. After cleavage of the Boc group under acidic conditions, the products 146 were cleaved from the support under basic conditions. In addition to alkynes, other dienophiles such as enol ethers could also be employed. 

Preparation of 146 The Diels-Alder reaction between 144 (50 mg, 74 pmol) and 10-20 equiv. of the dienophile in dioxane (4.0 mL) was performed for 16 h at reflux. The Boc group was then removed by stirring 145 in an excess of TFA/CH2CI2 (1 4) for 1 h. The product was released from the support by washing with CH2CI2 (three times) and MeOH/THF (twice), and treatment with K2CO3 in MeOH/THF for 12 h. After filtration, the filtrate was extracted with EtOAc. Concentration of the organic phase yielded the product 146. 

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