Samarium(ii) iodide-mediated reactions applied to natural product total synthesis

Abstract

Natural product synthesis remains a field in which new synthetic methods and reagents are continually being evaluated.

Aza-Achmatowicz rearrangement coupled with intermolecular aza-Friedel–Crafts enables total syntheses of uleine and aspidosperma alkaloids

“…As depicted in Scheme 3, the iAFC product 3ae (Table 2) was obtained in >26 g from 3b and used as the starting material for the synthesis of all aspidosperma alkaloids. The 6-exo-trig cyclization of 3ae failed to occur with samarium iodide (SmI 2 ) [102][103][104] or palladium catalysis (Heck) but could be realized via a radical mechanism by treatment with 1,1 0azobis(cyclohexane-1-carbonitrile) (V-40) and tributyltin hydride 105 under reuxed toluene to provide the tetracyclic core 1) with AAR products (2) a a Conditions1(0.2 mmol), 2(0.24 mmol), PCCP (0.01 mmol), toluene (1 mL), room temperature, 0.5-2 h. Yields in parentheses were obtained using TFA (15 mol%) as the catalyst. 14 (78% yield), which was common to all aspidosperma alkaloids.…”

Electrochemical Preparation of Sm(II) Reagent Facilitated by Weakly Coordinating Anions

“…Since its introduction to the synthetic community by Kagan and coworkers, samarium diiodide (SmI 2 ) has been widely used as a strong one-electron reducing agent in a broad range of synthetic organic reactions, including in the synthesis of antiviral, antibacterial, and anticancer natural products. [1][2][3][4][5][6][7][8][9][10] Despite their versatility, solutions of SmI 2 must contend with several disadvantages that limit their utility on large scale. [11] Many reactions that employ SmI 2 as a reducing agent require, at minimum, stoichiometric quantities of SmI 2 to achieve high yields.…”

Samarium-Mediated Asymmetric Synthesis

“…They can be categorized either as enantioselective or diastereoselective asymmetric synthesis [54][55][56]. Moreover, being highly oxophilic, the chelating effect of Sm(II) or Sm(III) ions to more than one Lewis basic center in either the substrates, additives or solvents induces significant stereoselectivity in the products through the formation of distinct transition states and intermediates [57,58].…”