Enantioselective Total Syntheses of Lyconadins A–E through a Palladium‐Catalyzed Heck‐Type Reaction

Abstract

A novel palladium‐catalyzed Heck‐type reaction of thiocarbamates has been designed to construct bridged seven‐membered‐ring systems that are otherwise challenging to prepare. Taking advantage of this newly developed method, enantioselective syntheses of lyconadins A–E (1–5), lycopecurine (6), and dehydrolycopecurine (7) have been realized in a divergent fashion. Our synthetic strategy also features an intramolecular cyclization of a N‐chloroamine to forge the C6−N bond, a transannular Mannich‐type reaction of a cyclic nitrone to stitch the C4 and C13 together, and a cyclocondensation to deliver the (dihydro‐)pyridone motif.

Catalytic Asymmetric Total Synthesis of Macrocyclic Marine Natural Product (–)‐Haliclonin A†

“…Notably, although our efforts to develop a catalytic Pd‐promoted intramolecular Heck‐type reaction was discontinued to focus on the total synthesis of haliclonin A, both the stoichiometric reaction [ 17c,d ] and the concept for a catalytic reaction [ 17e ] have inspired and prompted Yang's group to develop a catalytic version for related ring systems (Scheme 8), which enabled them to accomplish the total synthesis of lyconadins A—E. [ 38 ]…”

“…Recently realized Pd‐catalyzed cyclization of carbamothioate‐enone by Yang's group [ 38 ] …”

Metal-Free Solvent Promoted Oxidation of Benzylic Secondary Amines to Nitrones with H2O2

“… 6 Furthermore, the 1,3-dipolar cycloaddition reaction of nitrones with alkenes has become one of the methods of choice for the preparation of isoxazolidines, and a wide variety of natural products has been prepared using this reaction as key step. 7 …”

“…The diastereo- and enantioselective nucleophilic additions to nitrones is a fundamental tool in organic synthesis . Furthermore, the 1,3-dipolar cycloaddition reaction of nitrones with alkenes has become one of the methods of choice for the preparation of isoxazolidines, and a wide variety of natural products has been prepared using this reaction as key step …”

Organocatalytic Enantioselective 1,3‐Dipolar [6+4] Cycloadditions of Tropone

“…In as ingle synthetics tep employing simple commercially available starting materials, this protocol allows an efficient multicomponent reactionp roviding 8-azabicyclo[4.3.1]decane scaffolds, [10] embeddedw ith diversef unctional groups,w hose stereoselective transformations afford a varietyo fv aluable chiral compounds. Indeed, this structural motif represents the central core of bioactive Lycopodium and Daphniphyllum alkaloids, such as Lyconadines, [19] Daphnilactones and Yuzurimines. [20] Architectures containing this core are also found as pivotal intermediates in the synthesis of Fastigiatine and Himeradine(Scheme 1b).…”