A new route to the synthesis of the isocryptolepine alkaloid with antimalarial activity using a modified Pictet-Spengler reaction has been devised. The strategy was then used to generate libraries based on three structural variants of the alkaloid. Compounds based on these three variants in general were accessed in three steps through a modified PictetSpengler cyclization reaction as the key step. The C-2-, C-3-, or N-1-linked (aminoaryl)indoles (8, 12, 13) required for cyclization were obtained by treating the corresponding indoles with o-halonitrobenzene using either nucleophilic re-
An efficient method for the synthesis of new polycyclic skeletons: triaza-benzofluorenes and triaza-pentalenonaphthalene from bicyclic privileged structures imidazopyridine and imidazothiazole, respectively, has been described using the Pictet-Spengler cyclization.
A rapid, efficient and solvent‐free – green – protocol for Groebke–Bienaymé–Blackburn reaction (G−B‐B reaction) for the synthesis of fused‐imidazo heterocycles has been developed. The methodology reported here involves multi‐component reaction (MCR) catalyzed by reusable Yb(OTf)3 (a mild and water‐compatible Lewis acid) under microwave irradiation which allows fast and efficient preparation of the title compounds in excellent yield. The salient features of our protocol are solvent‐free, low catalyst loading (2.5–0.1 mol%) with good turnover number (TON: 890) and turnover frequency (TOF: 178/min), less reaction time (5 min), no dependency over specialized purification (by either column chromatography or recrystallization) and very high isolated yield (95–99 %) with excellent green chemistry metrics (E‐factor: 0.071 and Mass Intensity: 1.071). The water compatibility of the catalyst Yb(OTf)3 has been exploited for its efficient recovery through water washings. In addition, the other exciting milestones of the protocol are catalyst and workup solvent recycling, excellent conversion with notorious substrates such as enolizable aldehyde or isonitrile bearing reactive substituent, very efficient at higher scale (50 mmol) and easy to couple with other methods (one‐pot two‐step cyclization: G−B‐B reaction and Ullmann‐type coupling).
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