Synthetic approaches towards alkaloids bearing α-tertiary amines

Abstract

Alkaloids account for some of the most beautiful and biologically active natural products. Although they are usually classified along biosynthetic criteria, they can also be categorized according to certain structural motifs. Amongst these, the α-tertiary amine (ATA), i.e. a tetrasubstituted carbon atom surrounded by three carbons and one nitrogen, is particularly interesting. A limited number of methods have been described to access this functional group and fewer still are commonly used in synthesis. Herein, we review some approaches to asymmetrically access ATAs and provide an overview of alkaloid total syntheses where those have been employed.

Enzyme catalysed Pictet-Spengler formation of chiral 1,1’-disubstituted- and spiro-tetrahydroisoquinolines

“…1). However, compounds containing α-tertiary amines are typically challenging to synthesise2, and the use of unactivated ketones in the Pictet–Spengler reaction has been limited by their low reactivity and steric bulk.…”

Palladium‐Catalyzed Enantioselective Narasaka–Heck Reaction/Direct C−H Alkylation of Arenes: Iminoarylation of Alkenes

“…Extensive investigation by Bower and co‐workers demonstrated that, by tuning the nature of the ligand and the substrate structure, it is possible to generate dihydropyrroles/perhydroindoles with concurrent generation of a secondary or tertiary stereogenic center . This is of particular importance in view of the widespread presence of chiral‐nitrogen‐containing heterocycles in natural products and drugs . Very recently, Bower and co‐workers developed the first efficient catalytic asymmetric Narasaka–Heck reaction to give 2,5,5‐trisubstituted dihydropyrroles with good to excellent enantioselectivity (Scheme b) …”

Combination of Cp*RhIII‐Catalyzed C−H Activation and a Wagner–Meerwein‐Type Rearrangement

“…Theoxidative directing group [7] used herein plays several important roles,acting both as an internal oxidant and as an intramolecular nucleophile after the OÀNb ond cleavage.S ignificantly,t he present methodology affords ah ighly efficient way to construct the rearranged products [8] under mild reaction conditions with ahigh efficiency. Theoxidative directing group [7] used herein plays several important roles,acting both as an internal oxidant and as an intramolecular nucleophile after the OÀNb ond cleavage.S ignificantly,t he present methodology affords ah ighly efficient way to construct the rearranged products [8] under mild reaction conditions with ahigh efficiency.…”

“…Described herein is the successful coupling of N-phenoxyacetamide and 7-azabenzonorbornadiene for the efficient synthesis of bridged polycyclicm olecules,w hich combines C À Ha ctivation and Wagner-Meerwein-type rearrangement using aCp*Rh III catalyst (Scheme 2). Theoxidative directing group [7] used herein plays several important roles,acting both as an internal oxidant and as an intramolecular nucleophile after the OÀNb ond cleavage.S ignificantly,t he present methodology affords ah ighly efficient way to construct the rearranged products [8] under mild reaction conditions with ahigh efficiency.…”