First Asymmetric Synthesis of a Hasubanan Alkaloid. Total Synthesis of (+)-Cepharamine

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

“…[8] In light of the appealing molecular architecture and promising bioactivities of these compounds,s ignificant efforts have been devoted to the development of methods for the construction of this intriguing scaffold. [9] Undoubtedly,n ovel, efficient, and straightforward processes for the synthesis of this enantioenriched tricyclic skeleton would be highly desirable.Herein, we report an intermolecular asymmetric dearomatization reaction of b-naphthols with nitroethylene in achiral-thiourea-catalyzed Michael addition reaction. TheM ichael reaction between 1,3-dimethyl-2-naphthol (2a)a nd nitroethylene was chosen as am odel reaction to optimize the reaction conditions (Table 1).…”

Efficient Entry to the Hasubanan Alkaloids: First Enantioselective Total Syntheses of (−)‐Hasubanonine, (−)‐Runanine, (−)‐Delavayine, and (+)‐Periglaucine B

“…[10] However, the only enantioselective total syntheses of alkaloids bearing similarity to 2-5 are Schultzs synthesis of (+)-cepharamine [11] and Castles synthesis of (À)-acutumine. [12] Our approach was designed to permit access to a maximal number of targets.…”

“…[6] Hasubanonine (2) [7] and the related metabolites metaphanine [8] and cepharamine [9] have been previously prepared in racemic form, and numerous partial and formal syntheses of other hasubanan alkaloids have also been reported. [10] However, the only enantioselective total syntheses of alkaloids bearing similarity to 2-5 are Schultzs synthesis of (+)-cepharamine [11] and Castles synthesis of (À)-acutumine. [12] Our approach was designed to permit access to a maximal number of targets.…”

Short, Enantioselective Total Syntheses of (−)‐8‐Demethoxyrunanine and (−)‐Cepharatines A, C, and D

“…Although several hasubanans were prepared in racemic form by total synthesis in the early 1970s, [10,11] the enantioselective chemical synthesis of this family of compounds has proven far more challenging. The first enantioselective total synthesis of a hasubanan alkaloid was the 21-step synthesis of cepharamine (3) reported by Schultz and Wang in 1998. [12,13] As part of a program targeting the total syntheses of several alkaloid natural products, we sought to develop a unified strategy for the enantioselective preparation of the hasubanan and cepharatine alkaloids.…”

“…The first enantioselective total synthesis of a hasubanan alkaloid was the 21-step synthesis of cepharamine (3) reported by Schultz and Wang in 1998. [12,13] As part of a program targeting the total syntheses of several alkaloid natural products, we sought to develop a unified strategy for the enantioselective preparation of the hasubanan and cepharatine alkaloids. From the outset, the objective was to develop a synthetic approach that could provide access to any member of the hasubanan alkaloids, starting with the least oxidized members 1 and 3.…”