On the Asymmetric Iridium‐Catalyzed N‐Allylation of Amino Acid Esters: Improved Selectivities through Structural Variation of the Chiral Phosphoramidite Ligand

Abstract

The investigation of the iridium‐catalyzed asymmetric N‐allylation of tert‐butyl glycinate using a “branched” racemic 1‐vinyl‐alkyl methyl carbonate revealed severe limitations of existing protocols. By screening a set of 24 BINOL‐derived chiral phosphoramidites a new superior ligand (L24*) was identified which afforded the amination product with high enantioselectivity (≥95 % ee) under optimized conditions. This ligand also allowed the N‐allylation of other amino acid tert‐butyl esters (derived from alanine, phenylalanine, or proline) with outstanding levels of diastereocontrol (d.r. ≥99 : 1) and negligible matched/mismatched differences.

Chiral Amines via Enantioselective π-Allyliridium-C,O-Benzoate-Catalyzed Allylic Alkylation: Student Training via Industrial–Academic Collaboration

“…Consequently, considerable effort has been devoted to the development of enantioselective iridium-catalyzed allylic alkylations, especially in the context of C–N bond formation . Indeed, following seminal studies by Takeuchi, , asymmetric allylic aminations were developed in the laboratories of Helmchen, Hartwig, Carreira, You, and others . These processes invariably exploit chiral iridium-phosphoramidite catalysts, which have been categorized by Helmchen as type I or type II (Figure ).…”

“…Type II catalysts require acidic conditions and may be applied to branched π-allyl precursors (because π-enantiofacial interconversion is rapid with respect to alkylation) . Notably, like the parent palladium-catalyzed processes, type I and II iridium-phosphoramidite-catalyzed allylic alkylations proceed by way of cationic π-allylmetal intermediates. − Additionally, to promote high levels of branched regioselectivity, the iridium-phosphoramidite-catalyzed processes require aryl-substituted allyl proelectrophiles. Cyclometalated π-allyliridium- C , O -benzoates modified by SEGPHOS or tol-BINAP are structurally and functionally distinct from the iridium-phosphoramidite catalysts and, as described herein, have emerged as a third class of iridium catalysts for allylic alkylation.…”