One‐Step Synthesis of Racemic α‐Amino Acids from Aldehydes, Amine Components, and Gaseous CO₂ by the Aid of a Bismetal Reagent

Abstract

α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid can be divided into three basic components: an aldehyde, an amine, and carbon dioxide (CO(2)). We report herein that a one-step synthesis of α-amino acids has been successfully achieved from these three basic and inexpensive chemicals with a single operation, in which the mixture of an aldehyde, a sulfonamide, and gaseous CO(2) was heated at 100 °C in the presence of Bu(3)Sn-SnBu(3) and CsF. In this one-pot sequential protocol, two important intermediates (imine and α-amino stannane) are involved and the stannyl anion generated in situ plays a crucial role, particularly for the efficient stannylation of the imine in the presence of proton sources and for promoting retrostannylation of the undesired α-alkoxy stannane owing to its high stability and tolerance of the presence of proton sources. This methodology enabled the synthesis of a wide range of racemic arylglycine derivatives in high yields.

Transition Metal-Free Incorporation of CO2

“…This unique characteristic is applicable to the synthesis of amino acids by using gaseous CO 2 as carboxylating reagent. Arylglycine derivatives are prepared from the imine equivalents (N-Boc-R-amido sulfones 13) using a combination of TMS-SnBu 3 and CsF under CO 2 atmosphere as illustrated in Scheme 27 [103][104][105][106]. Reversal of polarity on the imino carbon atom is a key to the success of the proposed transformation, which could be accessed via α-metalation of alkylamine derivatives.…”

Syntheses of α‐Amino Acids by Using CO2 as a C1 Source

“…An imine, which is an intermediate in the one‐pot reaction of α‐amino sulfones, could also be accessed from an aldehyde and an amine component through dehydration. In 2013, we further developed the synthesis of α‐amino acids from aldehydes, amine components, and CO 2 (three fundamental reagents) in a single operation (Scheme ) . The one‐pot carboxylation reaction proceeded smoothly when using Bu 3 Sn−SnBu 3 as a bismetal reagent, thereby affording arylglycine derivatives in high yields.…”

One-Pot Synthesis of ^|^alpha;-Amino Acids from CO2 Using Bismetal Reagents

“…Actually, these three molecules could be incorporated ef ciently by the aid of the stannyl anion derived from Bu 3 Sn SnBu 3 and CsF with a single operation, giving tert butylsulfonyl protected α amino acids in up to 88% yield (Scheme 10). 35 Although less toxic silyl reagents did not promote this transformation, it is noteworthy that these three materials could be combined in one pot. As in the case of the one pot synthesis from α amino sulfones, two intermediates such as an imine and an α amino stannane were involved in this reaction.…”