Catalytic Asymmetric Synthesis of Unprotected β²-Amino Acids

Abstract

We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β2-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β2-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β2-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.

Catalytic Asymmetric Additions of Enol Silanes to In Situ Generated Cyclic, AliphaticN‐Acyliminium Ions

“…However, despite intense investigations during the last decade, none of our previously preferred acid catalysts led to promising results. Motivated by our studies on silylium‐based asymmetric counteranion‐directed catalysis ( Si ‐ACDC) with strong and confined acids, [33–55] we hypothesized that silylated IDPi catalysts should generate N ‐acyliminium ions from hemiaminal ethers and also enable efficient enantiofacial differentiation of these electronically and sterically unbiased cations.…”

Organocatalytic Asymmetric Double Addition of Kojic Acids to 2‐Nitroallylic Carbonates

“…Importantly, this interesting transformation can potentially be used for enantioselective synthesis of new chiral amino dicarboxylic acids. [19] Neither of the epimers 11 or epi-11 gave crystals suitable for X-ray analysis. Luckily, a high-quality co-crystal was produced from a solution of the mixture 11/epi-11 (70 : 30) in n-hexane/ CHCl 3 /MeOH (6 : 3 : 1) solvent system.…”

“…For analytical purpose, we also transformed diastereomeric mixture 10 aa / epi ‐ 10 aa (70 : 30) to mixed nitro‐dicarboxylates 11 / epi ‐ 11 in a similar way. Importantly, this interesting transformation can potentially be used for enantioselective synthesis of new chiral amino dicarboxylic acids [19] …”

Asymmetric Conjugate Addition of 3‐Hydroxychromen‐4‐Ones to Electron‐Deficient Olefins Catalyzed by Recyclable C2‐Symmetric Squaramide

“…Note that the reaction ent ‐ 3 al → ent ‐ 8 al is readily scalable. The prepared products ( R )‐ 7 aa and ( S ) ‐8 al are direct enantiomerically pure precursors to unprotected chiral β 2 ‐amino acids [30] …”