Asymmetric total synthesis of tacamonine (pseudovincamone I) via radical cyclization
TL;DR: The radical cyclization of (±)-(E)-3-((2-(bromomethyl)butoxy)carbonyl)-prop-2-enoates (11) and (12) were carried out with (TMS) 3 SiH or Bu 3 SnH in the presence of AIBN.
Abstract: The radical cyclizations of (±)-(E)-3-((2-(bromomethyl)butoxy)carbonyl)- prop-2-enoates (11) and (12) and (±)-ethyl (E)-3-{N-[2-(bromomethyl)- butyl]-N-[2-(3-indolyl)ethyl]carbamoyl}prop-2-enoate (25) were carried out with (TMS) 3 SiH or Bu 3 SnH in the presence of AIBN. (-)-(2S)-2- ((tert-Butyldimethylsilyloxy)methyl)butan-1-ol (6), which was prepared by two different methods, was converted into (+)-25. The radical cycli- zation of(+)-25 produced piperidinone (18) as a diastereomeric mixture, which was transformed into tacamonine (1)
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TL;DR: The total synthesis of the c Corynanthe alkaloid dihydrocorynantheol and the formal syntheses of the indole alkaloids tacamonine, rhynchophylline, and hirsutine are reported.
Abstract: We report herein the total synthesis of the corynanthe alkaloid dihydrocorynantheol and the formal syntheses of the indole alkaloids tacamonine, rhynchophylline, and hirsutine. The strategies for assembling the corynanthe and tacaman skeletal frameworks comprised of both the classical ABD → ABCD and ABC → ABCD approaches wherein the variously substituted piperidinone D-rings were formed via ring-closing metathesis (RCM) followed by a 1,4-addition to introduce the requisite side chain at C(15). Since 1,4-additions to α,β-unsaturated lactams represent an underdeveloped field, we conducted a series of studies with two unsaturated lactams employing organocuprates and metal enolates as the nucleophiles. These studies revealed that organocuprates derived from Grignard reagents and either stoichiometric amounts of CuCN or catalytic amounts of CuBr·DMS complex are excellent nucleophiles for such additions; TMSCl was a crucial additive for optimizing these reactions. The anion derived from ethyl 1,3-dithiolane-2-c...
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TL;DR: The asymmetric acylation of meso-2-substituted-1,3-propanediols by using an amphoteric chiral dinuclear zinc catalyst is described and both enantiomers of the desymmetrized product can be obtained from the same starting material.
Abstract: The asymmetric acylation of meso-2-substituted-1,3-propanediols by using an amphoteric chiral dinuclear zinc catalyst is described. It is has been demonstrated that both 2-alkyl- and 2-aryl-1,3-propanediols can be desymmetrized in high yields and enantioselectivities by using the same family of ligands. Given that both antipodes of the chiral catalyst are available, both enantiomers of the desymmetrized product can be obtained from the same starting material. The synthetic utility of the desymmetrized products has been demonstrated by the synthesis of several chiral building blocks with high enantiomeric purities.
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