Total Synthesis of (−)-Conolutinine

Abstract

The first enantioselective synthesis of (-)-conolutinine was achieved in 10 steps. The synthesis featured a catalytic asymmetric bromocyclization of tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed by Co(acac)2 was also employed as a key step to diastereoselectively introduce the tertiary alcohol moiety. The absolute configuration of (-)-conolutinine was established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis.

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

“…219 Acid mediated hydration conditions were incompatible with the functionalities present in 122 . The authors explored a variety of metal salts, particularly of iron and cobalt, known to effect radical oxidation.…”

Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)‐Tronocarpine Enabled by an Asymmetric Michael/Aldol Reaction

“…A chiral catalyst with appropriate ion‐pairing and H‐bonding functionalities as scaffolding elements is expected to form a more rigid transition‐state conformation with the substrates through proper positioning of the interaction sites, and thereby induce better regio‐ and enantioselectivity than a catalyst possessing a single interaction site. Accordingly, a few tartrate‐derived chiral guanidine catalysts were examined using 12 a (Figure ) as a model compound, which could be readily prepared on over a 10 g scale from the known compound 11 through reduction followed by substitution with TMSCN . Disappointedly, the desired reaction did not proceed, with the starting material remaining intact under various conditions, presumably owing to the weak basicity of guanidines.…”

Highly Enantioselective Tandem Michael Addition of Tryptamine‐Derived Oxindoles to Alkynones: Concise Synthesis of Strychnos Alkaloids

“…Since the milestone synthesis of strychnine by Woodward and coworkers, [4] thechallenging and complex structure of strychnos alkaloids has long served as an inspiration for new synthetic methods and strategies. [3,5,7] As ac ontinuation of our work on the synthesis of indole alkaloids, [8] we hypothesized that enone 1 could serve as av ersatile building block for the synthesis of strychnos alkaloids by adding the bridged Dr ing through allylic substitution after reduction of the enone moiety.R etrosynthetically,t his intermediate could be accessed through intramolecular condensation of spiro[pyrrolidine-3,3'-oxindole] 4 ( Figure 1). [6] Although spiro[pyrrolidine-3,3'-oxindole] contains the core structure (A, B, and Cr ings) present in those two type of indole alkaloids (Figure 1), its application in the synthesis of strychnos alkaloids has never been explored.…”

“…[6] Although spiro[pyrrolidine-3,3'-oxindole] contains the core structure (A, B, and Cr ings) present in those two type of indole alkaloids (Figure 1), its application in the synthesis of strychnos alkaloids has never been explored. [3,5,7] As ac ontinuation of our work on the synthesis of indole alkaloids, [8] we hypothesized that enone 1 could serve as av ersatile building block for the synthesis of strychnos alkaloids by adding the bridged Dr ing through allylic substitution after reduction of the enone moiety.R etrosynthetically,t his intermediate could be accessed through intramolecular condensation of spiro[pyrrolidine-3,3'-oxindole] 4 ( Figure 1). Drawing inspiration from previous work on tandem mixed Michael addition [9] and enantioselective addition of oxindoles to alkynones, [10] we surmised that tandem Michael addition of tryptamine-derived oxindole 2 to alkynone 3 through intermolecular carbon-Michael addition followed by intramolecular aza-Michael addition via oxindole I would give rise to the desired spirooxindole 4.H erein, we report the enantioselective construction of spiro[pyrrolidine-3,3'-oxindolines] through this tandem process promoted by chiral N,N'-dioxide Sc(OTf) 3 complexes.…”