A Vaulted Biaryl Phosphoric Acid-Catalyzed Reduction of α-Imino Esters:  The Highly Enantioselective Preparation of α-Amino Esters

Abstract

Chiral amino acids are some of the most important small molecules found in biological systems. Natural and unnatural R-amino acids are also highly utilized in academia and in the pharmaceutical, biotech, and chemical industries. Therefore, the discovery of general methodology that can produce chiral R-amino acid derivatives in high yield and with useful levels of enantioselectivity is of considerable importance. 1

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

“…Reactions with imines bearing large N‐substituents favor Type I pathways; a preference for E or Z depends on how accessible the configuration is. If the Z configuration is energetically inaccessible the reaction proceeds via a Type I  E pathway, the correct catalyst has large proximal and medium AREA(θ) 10, 11, 12, 13c, 14b, 19, 20, 21, 22, 40, 41, 42, 43, 44, 45, 46, 47. However, reactions involving displaced nucleophiles the best choice of catalyst has large proximal and small AREA(θ) 5, 8, 9, 30, 31, 48, 49, 50, 51, 52, 53.…”

The Enantioselective, Brønsted Acid Catalyzed, Vinylogous Mannich Reaction

“…[7] Such chiral Brønsted acids have proven to be exceptional chiral catalysts for a broad range of highly enantioselective imine addition reactions which involve chiral contact ion pairs generated in situ. [8][9][10][11][12][13] In this context, Akiyama and co-workers have already developed highly enantioselective normal Mannich reactions of silylketene acetals with Brønsted acid of this type. [7a, b] As a model reaction, we chose the reaction of imine 1 a and TBS-substituted dienolate 2, [14] which led to the vinylogous Mannich product 3 a, and investigated various phosphoric acids 4 a-f (each 30 mol %) in toluene at 0 8C (Table 1 and Scheme 1).…”

A New Pyridyl Bis(oxazoline) Ligand Prepared from D‐Glucosamine for Asymmetric Alkynylation of Imines

“…Encouraged by this result, which is on par with the selectivities achieved by Li and Singh with pybox ligands from non-natural precursors, we explored other substrates. For a broad application of the reaction, employing 4-methoxyaniline as the amine component is desirable, as the p-methoxyphenyl (PMP) residue can be oxidatively cleaved [17] to access free propargylamines. Regarding the alkyne component, silylacetylenes are attractive substrates as the silyl groups can be removed as well yielding a product with a terminal alkyne moiety for further elaboration.…”