DMD Mediated Formal Synthesis of (±)-Coerulescine

Abstract

A highly efficient method for the formal synthesis of the natural product (±)-coerulescine 1 from tetrahydro-β-carboline 3, mediated by dimethyldioxirane (DMD), is described. Compound 15, the N9-demethylated precursor of 1, was prepared from 3 in 4 steps with an overall yield of 95%. The effect of electron withdrawing groups at the N2,N9 atoms of 3 was explored for the oxidative rearrangement step.

Lewis Acid-Catalyzed Diastereoselective Domino Reaction of Ene-Ynamide with Trimethylsilyl Cyanide to Construct Spiroindolines

“…Further derivatization of the cyano group in 4 , for example, esterification, was conducted to afford ester 5 in 68% yield. Finally, we applied our methodology to produce from 1g of known spiroindoline 6 that can be converted to coerulescine (see Figure ) as reported by the Suárez-Castillo group …”

“…Finally, we applied our methodology to produce from 1g of known spiroindoline 6 that can be converted to coerulescine (see Figure 1) as reported by the Suaŕez-Castillo group. 15 In summary, we developed an efficient method for Lewis acid-catalyzed domino cyclization of enamide-ynamides 1 with external nucleophiles to yield spiroindolopyrrolidine derivatives 2 with high diastereoselectivity. We also demonstrated additional application of the obtained product, such as formal natural product synthesis.…”