Examples of Solid-Phase Discrete Library Synthesis

3 EXAMPLES OF SOLID-PHASE DISCRETE LIBRARY SYNTHESIS 

A recent paper by Kiselyov et al. (91) reported the synthesis of two small SP discrete libraries of tetrahydroquinolines LI and L2 inspired by a three-component condensation reaction in solution (92-94) as depicted in Eig. 6.8. The scope of this condensation had been expanded by other groups (95-97), and the use of polymer-supjxMted metal catalysts had also been reported (98, 99) however, an SP route with a broad tolerance for different amines, aldehydes, and olefins had still not been defined prior to this work. 

The authors first considered the attachment of the aldehyde component to the SP using the AMEBA (acid-sensitive methoxy benzaldehyde) PS resin (100). 4-Carboxy-benzaldehyde and two different amines were reacted to produce the resin-bound intermediates 6.1 and 6.2 on a 100-g scale according to the reaction scheme shown in Pig. 6.9, with good yields resulting from an optimization of the reaction conditions. Resin-bound 6.1 was reacted with the standard olefin (cyclopentadiene, 6.3) and an aromatic amine (aniline, 6.9) and, after optimization of the reaction conditions, the desired tetrahydroquinoline 6.14 was obtained in good yield and purity after cleavage. 

The corresponding Schiff base was obtained as the only impurity in amounts ranging from 2 to 7% during the various chemical assessment runs. Compound 6.14 was formed as a single diastereomer with the relative orientation of the three chiral centers as shown. 

These encouraging results prompted the authors to prepare an SP discrete library of 60 individuals, LI, using the two solid-supported aldehydes 6.1 and 6.2, six olefins (6.3-6.8), and five substituted anilines (6.9-6.13), whose structures are reported in 

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