Tetrahydroquinolines, solution-phase

Related heteroannulation chemistry has been conducted on the solid-phase and provided new routes to hydrobenzofu-rans, hydrobenzopyrans, indolines and tetrahydroquinolines. Using alkenyl-based substrates in solution-phase variations of such processes has led to ( -2-alkyl(aryl)idene-l,2,3,4-tetrahydroquinoxalines and pyrido[2,3-4]p3Timidines. ... 

Derivatization of functional groups in a natural-product scaffold can also be effectively performed on the solid-phase. An example of this is the synthesis of a small compound collection (27-compounds) based on the tetrahydroquinoline scaffold. A chiral tetrahydroquinoline scaffold was synthesized in solution from 5-hydroxy-2-nitrobenzaldehyde (Scheme 4). The synthesis involved a key asymmetric aminohydroxylation step. This building block was anchored to the solid support with a Wang linker and diversity was introduced by selective deprotection and derivatization of the protected hydroxyl and amino substituents. 

Fig. 17.10 Modular solution and solid phase approaches to obtain tetrahydroquinoline based tricyclic compounds containing different unsaturated lactam rings and macrocyclic rings, (a) (i) 20% piperidine, CH2CI2 (ii) Et3N, ac loyl chloride, —10°C, CH2CI2 (iii) ...

Fig. 17.12 In situ bridged aza Michael approach in solution and on solid phase to obtain tetrahydroquinoline-based tricyclic compounds, (a) (i) acetic acid/THF/H20, RT (ii) TESOTf, pyridine, CH2CI2, -40°C (iii) Pd(PPh3)4, morpholine, CH2CI2, RT (c) Et3N, benzoyl chloride or cinnamoyl chloride, CH2CI2, O C to RT.

Arya, P. et al., Solution- and solid-phase synthesis of natural product-like tetrahydroquinoline-based... 

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