Asymmetric Total Synthesis of (−)-Aspidophylline A

Abstract

An asymmetric total synthesis of (-)-aspidophylline A has been accomplished. The key transformations include an asymmetric hydride transfer hydrogenation of an α,β-acetylenic ketone and a cationic gold(I)-catalyzed 6-exo-dig cyclization involving an alkynylindole/aminal formation cascade, which enables stereoselective establishment of the requisite quaternary carbon center.

Intramolecular Heck Reaction in Total Synthesis of Natural Products: An Update

“…Compound 8 finally transmuted to natural product 9 . In 2016, Zhai et al [3c] . also have completed the total synthesis of (−)‐aspidophylline A ( 9 ) through the same intermediate 8 via Heck cyclization with 68 % yield ( d : r 5 : 1).…”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…Treatment of in situ deprotected propargyl alcohol derivativew ith 5mol % PPh 3 AuCl in the presence of co-catalyst AgSbF 6 resulted the cyclization product 648.F urther transformations of 648 via generation of the tetracyclic framework, akuammiline alkaloid (À)-aspidophylline Awas achieved( Scheme 164). [186] In 2011, Fujii and Ohno reported total syntheses of (+ +)-lysergic Acid 655,( + +)-lysergol 651,a nd (+ +)-isolysergol 652 by utilizing indole-tethered propargyl alcohols as keys ynthons. [187] Asymmetric formal synthesis of (+ +)-lysergic acid involving a Zn(OTf) 2 promoted regio-and stereoselective reductiveo xirane ring openingo f2 -alkynyl-3-indolyloxirane 653 by NaBH 3 CN was also achieved by the same group (Scheme 165).…”

“…Further transformations of 648 via generation of the tetracyclic framework, akuammiline alkaloid (−)‐aspidophylline A was achieved (Scheme 164). [186] …”

Alkaloid Synthesis via Gold‐Catalyzed Carbon‐Carbon Bond Formation Using Enamine‐type Nucleophile

“…Following the protocol developed by X. Wang and co‐workers, the Zhai group designed a new route to synthesize alkaloid (−)‐aspidophylline A (Scheme ) . For the key gold catalysis, 48 bearing a chiral secondary alcohol was employed as substrate, and the transformation features a 6‐ exo ‐dig cyclization followed by tetrahydrofuran formation through trapping of the iminium intermediate by the alcohol.…”