Aldehydes, reaction with indole Grignard

The first total synthesis of cinchonamine (277) and 2-epicinchonamine (278) proceeds via the epimers (279), which were prepared by two independent methods.169 Scheme 28 illustrates the more efficient of the two syntheses, which involves as its first stage the condensation of 2-lithio-iV-benzenesulphonyl-indole with N-benzoylmeroquinene aldehyde (280), itself obtained by reduction of the readily available JV-benzoylmeroquinene ester (281). The critical cyclization stage [(279)— (283)+ (284)] that occurs on prolonged heating at 155 °C presumably proceeds via the immonium ion (282), since separation of the epimers of (279) followed by dehydration and cyclization affords the same mixture of (283) and (284). Finally, the hydroxyethyl group was introduced by the reaction of the Grignard derivatives of (283) and (284) with ethylene oxide.169... 

Indolyl A-Grignards, "" or even better their zinc analogues, undergo reaction predominantly at C-3 with a variety of carbon electrophiles such as aldehydes, ketones and acid halides, or reactive halo-hetero-cycles. Including aluminium chloride in the zinc reactions produces high yields of 3-acyl-indoles. The copper-catalysed reactions of indolyl-A-Grignards with A-t-butoxycarbonyl-aziridines also proceed well at C-3. ... 

---