Synthesis of the Common Propellane Core Structure of the Hasubanan Alkaloids

Abstract

The racemic synthesis of the common propellane core structure found in various hasubanan alkaloids is reported. The successful completion hinged upon the stereocontrolled construction of the cis-substituted heterobicycle as a precursor for the intramolecular Dieckmann condensation. A novel strategy is introduced for the facile hydrolysis of a sterically demanding carboxamide under a mild condition. The 2-nitroanilide obtained by the Goldberg arylation of a carboxamide with 2-iodonitrobenzene was readily converted to the corresponding ester derivative by way of N-acylbenzotriazole. We expect that the reported synthetic route will allow the synthesis of a series of hasubanan alkaloids starting from the correspondingly functionalized 2-tetralone derivatives.

Diamine ligands in copper-catalyzed reactions

“…221 Kobayashi engaged an intermolecular Cu-catalyzed arylation of an amide in the synthesis of hasubanan alkaloids, a group closely related to the morphine alkaloids (Scheme 64). 222 …”

Asymmetric Dearomatization of β‐Naphthols through a Bifunctional‐Thiourea‐Catalyzed Michael Reaction

“…Treatment of product 3 j (92 % ee ) with L ‐selectride followed by reduction with LiAlH 4 and chemoselective protection of the resulting amino alcohol with Boc 2 O afforded carbamate 7 in an overall yield of 22 % over three steps with good diastereoselectivity (86 % ee , 4:1 d.r.). Carbamate 7 is a key intermediate in the synthesis of the propellane core structure of the hasubanan alkaloids 12. This procedure thus also presents a novel approach towards the hasubanan alkaloid family.…”

“…Carbamate 7 is ak ey intermediate in the synthesisofthe propellane core structure of the hasubanan alkaloids. [12] This procedure thusa lsop resents anovel approach towards the hasubananalkaloid family.…”

Development of new methods in modern selective organic synthesis: preparation of functionalized molecules with atomic precision

“…Recently, the synthesis of the alkaloid hasubanonine belonging to the hasubanan family was performed. 377 The key step in this synthetic route is the Strecker reaction involving imine 79f (Scheme 96). The target compound 97 was isolated as the only diastereomer in a high yield (87%).…”