Tandem aza-Michael/spiro-ring closure sequence: access to a versatile scaffold and total synthesis of (±)-coerulescine

The total synthesis of the alkaloid (+/-)-coerulescine is presented. The key step of this approach is an efficient tandem aza-Michael initiated ring closure (aza-MIRC) process between ethoxymethylene-oxindole and benzyl(2-bromoethyl)carbamate. The potency of the aza-MIRC reaction was first tested onto less challenging Michael acceptors and led in good yields to the corresponding N-Cbz alpha-alkoxy-beta-gem-disubstituted pyrrolidines. The resulting N-acyliminium precursor obtained from ethoxymethylidene-oxindole was efficiently converted in four steps, including 2 deprotections, into the targeted (+/-)-coerulescine. (C) 2013 Elsevier Ltd. All rights reserved.