The enantioselective intramolecular aminative functionalization of unactivated alkenes, dienes, allenes and alkynes for the synthesis of chiral nitrogen heterocycles

Abstract

The enantioselective intramolecular aminative functionalization of unactivated alkenes and related π-systems is a straight-forward and atom economical strategy for the synthesis of chiral nitrogen heterocycles. These reactions can be categorized as oxidatively neutral, such as alkene hydroamination, or as oxidative reactions, such as alkene difunctionalization, e.g. aminooxygenation and carboamination. This perspective reviews the current work in the field and explores mechanistic trends that are common among the different catalysts and reaction types.

Scheme 1

Proposed mechanism of Marks’ enantioselective lanthanide catalyzed alkene hydroamination with a C₂-symmetric bis(oxazoline) ligand.

Scheme 2

Chiral bis(oxazoline) ligands in enantioselective lithium-catalyzed hydroamination reactions.

Scheme 3

Proposed catalytic cycle for the gold-catalyzed hydroamination of allenes.

Scheme 4

Proposed catalytic cycle for the intramolecular hydroamination of alkynes.

Scheme 5

Palladium-catalyzed enantioselective S_N2′-type cyclization.

Scheme 6

Proposed catalytic cycle for the enantioselective copper-catalyzed alkene carboamination.

Scheme 7

Application of the copper-catalyzed carboamination to the total synthesis of (+)-tylophorine.

Scheme 8

Proposed cycle for the copper-catalyzed enantioselective alkene aminooxygenation.

Fig. 1

Other lanthanide–ligand complexes used for asymmetric alkene hydroamination.

Fig. 2

Origin of the enantioselectivity in the hydroamination reactions with Schafer’s catalyst.