Enantioselective Michael/aza‐Michael/Cyclization Organocascade to Tetracyclic Spiroindolines: Concise Total Synthesis of Kopsinine and Aspidofractine

Abstract

The method succeeds for indole derivatives equipped with electron‐donating substituents on the benzene ring, but fails with the electron‐withdrawing fluoro‐substituent.

Tandem Cross‐Coupling/Spirocyclization/Mannich‐Type Reactions of 3‐(2‐Isocyanoethyl)indoles with Diazo Compounds toward Polycyclic Spiroindolines

“…The Mannich‐type cyclization of one of the diastereoisomers would have to be faster than the other, resulting in a diastereomerically enriched product. Inspired by these results, we then tested a series of chiral phosphoric acids with the aim to explore a catalytic asymmetric process to assemble pentacyclic spiroindolines, which remains challenging, and few examples have so far been reported . After screening of reaction conditions, we found that the utilization of 15 mol % chiral phosphoric acid ( S )‐ CP10 in ClCH 2 CH 2 Cl at −10 °C or 0 °C was optimal to form 4 a with good yield (65 %) and moderate enantioselectivity (87:13 er; see the Supporting Information for details).…”

Synthetic Approaches to Tetracyclic Indolines as Versatile Building Blocks of Diverse Indole Alkaloids

“…An enantioselective Michael/aza‐Michael/cyclization organocascade cascade annulation reaction was developed by Wu and co‐workers to access the core structures of Kopsia alkaloid in 2014 (Scheme ) . The annulation cascade was initiated with an organocatalytic Michael addition of tryptamine derivative to the propargyl aldehyde.…”

“…[25] An enantioselective Michael/aza-Michael/cyclization organocascade cascade annulation reaction was developed by Wu and co-workerst oa ccess the core structures of Kopsia alkaloid in 2014 (Scheme 6). [26] The annulation cascade was initiated with an organocatalytic Michael addition of tryptamine derivative to the propargyl aldehyde. Then af ollowing aza-Michael additon of carbamate to the a,b-unsaturated iminium afforded aldehyde 54.A tl ast, the cyclization by the addition of the enamine to the aldehyde and spontaneousd ehydration and tautomerization would readily afford the tetracyclic indoline 55 in moderate to good yields (56-78 %) and excellent enantioselectivities (84-96 % ee).…”

“…Scheme6.Enantioselective Michael/aza-Michael/cyclization organocascade to tetracyclic indoline 58 (Wu et al [26] ). lized as significant buildingb locks by taking advantage of the substantial advancements in ynamide chemistry in the past decade.…”

Enantioselective Construction of Spiroindolines with Three Contiguous Stereogenic Centers and Chiral Tryptamine Derivatives via Reactive Spiroindolenine Intermediates

“…[1,2] In this regard, great effort has been devoted to the development of enantioselective construction of these skeletons. [4,5] However,t he diastereoand enantioselective control usually suffers when the vicinal tertiary and all-carbon quaternary stereocenters are generated in the dearomatization process. [4,5] However,t he diastereoand enantioselective control usually suffers when the vicinal tertiary and all-carbon quaternary stereocenters are generated in the dearomatization process.…”