Studies on the Regioselectivity of the Cyclization of Tryptophanol‐Derived Oxazolopiperidone Lactams

Abstract

Cyclization of the lactam carbonyl on the indole ring in tryptophanol‐derived oxazolopiperidone lactams 2 and 6, under the classical POCl3‐promoted Bischler–Napieralski conditions and under neutral conditions via the corresponding thiolactam, has been studied. Whereas tricyclic lactam 2 only leads to products coming from an α‐amidoalkylation process, bicyclic lactam 6 undergoes cyclization on the lactam carbonyl, leading to the expected indolo[2,3‐a]quinolizidine derivatives.

Scaffold Diversity from N-Acyliminium Ions

“…The same group also reported the application of ( S )-tryptophanol as a starting material for the synthesis of other spiro compounds, such as ent -rhynchophylline and ent -isorhynchophylline . This type of α-aminoalkylation reaction has also been carried out with benzylic N -thioacyliminium ions …”

“…178 This type of α-aminoalkylation reaction has also been carried out with benzylic N-thioacyliminium ions. 179 5.2.2. Other Aromatic Nucleophiles.…”

Enantioselective Synthesis of Spiro[indolizidine-1,3′-oxindoles]

“…Previously, we reported stereoconvergent cyclocondensation reactions between tryptophanol and δ-oxoesters A , either prochiral or as mixtures of stereoisomers, leading to enantiopure oxazolopiperidone lactams B , which can undergo three complementary regio- and stereocontrolled types of cyclization to form either indolo­[2,3- a ]­quinolizidines C or D , or spiro­[indoline-3,1′-indolizidines] E (Scheme ).…”