Enantioselective Total Synthesis of (−)-Limaspermidine and Formal Synthesis of (−)-1-Acetylaspidoalbidine

Abstract

Evolution of the synthetic strategy that culminated in the first asymmetric total synthesis of the Aspidosperma alkaloid limaspermidine is described. The successful enantioselective route to (-)-limaspermidine proceeds in 10 steps and with the isolation of only six intermediates using a Pd-catalyzed enantioselective decarboxylative allylation we have recently developed. This first enantioselective synthesis of (-)-limaspermidine establishes unambiguously its absolute configuration and allows the first asymmetric formal total synthesis of the Aspidoalbine alkaloid (-)-1-acetylaspidoalbidine.

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…Then, 573 was converted to (À)-568 through RANEY®-Co-mediated reductive cyclization, conrm-ing its absolute conguration (Scheme 119). 185 The oxidative 1,3-alkyl shi process of phenol 575 leading to allenyl dienone 577 with a quaternary carbon center was developed by Canesi's group, which involved intramolecular trapping of phenoxonium ion 576 with an alkyne group. The resulting 577 was elaborated to form 569 through the formation of tricyclic ketone 578 followed by the Fischer indolization (Scheme 120).…”

Enantioselective Catalysis Coupled with Stereodivergent Cyclization Strategies Enables Rapid Syntheses of (+)‐Limaspermidine and (+)‐Kopsihainanine A

“…We anticipated that such an intermediate could be advanced to members of the Aspidosperma family of alkaloids,s uch as (+ +)-limaspermidine (2). [7] Alternatively,b yr eversing the order of these events (CÀCf ormation then CÀHf ormation), aB ischler-Napieralski cyclization could furnish tetracyclic iminium 12, and the ensuing hydride reduction would proceed from the less hindered a-face to give the trans-fused octahydroquinoline subunit in tetracycle 13 (Scheme 1B,r ed path). [8] We expected that 13 could then be carried on in atotal synthesis of (+ +)-kopsihainanine A( 3)a nd additional Kopsia alkaloids.…”

Synthesis of Spirocyclic Indolenines

“…[95] Shao, Peng and co-workers have also applied this strategy in natural product synthesis, to form similar pentacyclic frameworks 148 and 150 in good yields. [96,97] Finally Weinreb and co-workersr eported the cyclopropanation spirocyclisation of 151,w hich upon treatment with either AgOTf or AgBF 4 ,a fforded the spirocyclic indolenine 152 in excellent yield. [98] Intramolecular Mitsunobu reactions have also been shown to be effective for spirocyclic indolenine synthesis (Scheme22).…”

“…Banwell and co‐workers also used a AgOTf promoted alkylation of 145 in their total synthesis of (±)‐limaspermidine and (±)‐1‐acetylaspidoalbidine precursor 146 . Shao, Peng and co‐workers have also applied this strategy in natural product synthesis, to form similar pentacyclic frameworks 148 and 150 in good yields . Finally Weinreb and co‐workers reported the cyclopropanation spirocyclisation of 151 , which upon treatment with either AgOTf or AgBF 4 , afforded the spirocyclic indolenine 152 in excellent yield …”