Pictet-Spengler cyclization polycyclizations

Another example of Ugi/Pictet-Spengler two-step procedure was employed by El Kaim et al. to prepare polycyclic 1,4-diketopiperazines 228 [69]. The four-component Ugi reaction of homoveratryl isocyanide 229 and a-ketocarboxylic acids 230 allows the formation of Ugi products, which were treated with trifluor-oactic acid to afford tricychc 2,5-diketopiperazines 228 in a Pictet-Spengler-type cyclization (Scheme 42). 

Cyclization of iminium ions onto arenes were first described by Pictet and Spengler in 1911, with the formation of tetrahydroisoquinoline 152 (Equation 10) [125]. This versatile transformation has been widely used in the diastereoselective synthesis of polycyclic aromatic alkaloids of biological interest, in particular of tetrahydro-/5-carbolines 154 (Equation 11) [126]. A few selected examples that highlight stereoselective Pictet-Spengler reactions are discussed below [9, 103, 127]. 

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