Asymmetric Synthesis of Quaternary α‐Amino Acids and Their Phosphonate Analogues

Abstract

Asymmetric synthesis of α‐amino acids and their phosphonate analogues has received considerable attention due to their diverse biological activities. Quaternary α‐amino acids and their phosphonate analogues are often more resistant to chemical and enzymatic degradation and therefore have been targets of various synthetic endeavors. This Focus Review provides a summary of recent approaches to catalytic asymmetric synthesis of quaternary α‐amino acids and α‐aminophosphonates.

Complete diastereodivergence in asymmetric 1,6-addition reactions enabled by minimal modification of a chiral catalyst

“…4)5051. Harnessing the structural feature of 4 , possessing two differentiated functionalities of carboxylic acid oxidation state, the acyl pyrrole unit was selectively transformed into methyl ester by treatment with sodium methoxide in methanol52.…”

"Synthesis of 3-(3-Methoxy-2-Nitro-3- Phenylpropyl)-9h-Carbazole From Friedel-Crafts Reaction"

“…[1][2][3][4][5] The B-H reaction is a new carbon-carbon bond forming reaction producing a functional class of well-applied molecules and the adducts have been employ for various organic transformations. [6][7][8][9][10] The Baylis-Hillman adducts have been successfully utilized as synthons in numerous named reactions for example Heck reaction, Diels-Alder reaction, Aldol condensation, Claisen rearrangement, Friedel-Crafts reation [11][12][13][14][15] etc. The Friedel-Crafts reaction is one of the most commonly used reactions in organic chemistry whose applications in intellectual as well as industrial fields have been well documented.…”

Recyclable Ligands for the Non‐Enzymatic Dynamic Kinetic Resolution of Challenging α‐Amino Acids

“…[6,7] Among various approaches to enantiomerically pure TMa-AAs, [6][7][8] the dynamic kinetic resolution (DKR) of racemates is unarguably the most economic solution, especially on alarge scale.[9] However,the choice of methods available for such processes is overwhelmingly dominated by biocatalytic procedures, [10] whereas purely chemical methods [11] have been disproportionally underdeveloped and prohibitively expensive.[12] Therefore,t osurpass the exceptional efficiencyo f enzymatic approaches, [10] ap urely chemical method should feature an ingenious combination of simple and high-yielding reactions,o perationally convenient conditions, [13] as well as inexpensive starting materials and ar ecyclable source of chirality.A sp art of our long-term interests in the development of practical methods for the preparation of TM-a-AAs and TM-b-AAs [14, 15] and drawing inspiration from work by Chin and co-workers, [16] we have recently been focusing on the development of new types of chiral ligands that are suitable for direct and practically useful DKR reactions of unprotected TM-a-AAs.In particular,compounds 1 and 2,which were reported by Chin [16] and co-workers and ourselves, [17] are considered as the best-performing ligands for the direct DKR of unprotected TM-a-AAs (Figure 1). Forb oth types of ligands,D KR proceeds via the corresponding Schiff base intermediates followed by thermodynamic equilibration of the resulting diastereomers.However,ligands 1 and 2 also share the same shortcomings:1 )They completely fail in the DKR of amino acids with tertiary side chains,a nd 2) as they are based on axially chiral 1,1'-binaphthyl moieties,they are rather expensive to rival the economic efficiencyofenzymatic methods for the large-scale preparation of TM-a-AAs.C ontinuing our work on modular approaches to chiral ligands, [18] we identi- Figure 1.…”