Synthesis of Unnatural α-Amino Acids via Photoinduced Decatungstate-Catalyzed Giese Reactions of Aldehydes

Abstract

Synthesis of unnatural amino acids has long been a focus of chemistry research. Here, we present an efficient, general method that furnishes γ-carbonyl α-amino acids via photoinduced decatungstate-catalyzed Giese reactions of readily available aldehydes as radical precursors. This mild, robust method is compatible with a wide array of functional groups and has a broad substrate scope. We demonstrated the utility of the method by modifying several amino acid bearing drugs and natural products.

Chiral Phosphoric Acid‐Catalyzed Enantioselective Synthesis of Pyrazole‐Based Unnatural α‐Amino Acid Derivatives

“…As a result, considerable effort has been made to construct other highly valuable unnatural α‐amino acid scaffolds, and a number of elegant methods have been reported [12] . For example, palladium‐catalyzed C( sp 3 )−H functionalization, [4a,13] visible light‐mediated decarboxylative conjugate addition to dehydroalanine, [14] photoinduced decatungstate‐catalyzed Giese reaction of aldehydes, [15a] iron catalyzed reactions of 2‐phthaloyl acrylamide with alkenes [7b] and olefin‐olefin coupling via generated radicals, [15b] and copper‐catalyzed reactions of amino acid‐derived Schiff bases [15c] were established. In addition, the synthesis of asymmetric versions of unnatural amino acids using a simple chiral amido‐thiourea catalyst, [16] the hydrogenation of N ‐acetylamino‐phenylacrylic acids using a chiral ruthenium catalyst, [3] and via visible‐light‐promoted photoredox catalysis have been developed [16b] …”

Expedient access to N-alkylphthalimides via redox-neutral photocatalysed Giese-type reactions

“…4 In addition to the above-mentioned pathways, the radical-involved synthesis of N -alkylphthalimides has been reported via the reactions of N -vinylphthalimide with various radicals (Scheme 1, path d). 5 Considering the wide synthetic utility of N -substituted phthalimides, a general and efficient protocol for the modular access to N -alkylphthalimides is still highly desirable. 6…”

Synthesis of γ-Oxo-α-amino Acids via Radical Acylation with Carboxylic Acids

“…Since II is a highly versatile species, we became interested in developing alternative methodologies for its synthesis using more readily available starting materials. 12 Recently, the development of deoxygenative radical strategies to access acyl radicals has attracted increased attention. 13 Seminal independent studies by Rovis and Doyle 13e and Zhu 13d described the use of photoredox catalysis to generate phosphine radical cations that swiftly react with carboxylates to generate acyl radicals and phosphine oxide after β-scission (vide infra).…”

“…The Journal of Organic Chemistry 8,172.2,155.7,152.2,148.5,135.3,131.3,128.7,128.6,128.5,124.6,108.1,108.0,102.1,96.3,68.3,53.9,41.7,37.5,24.9. HRMS (ESI) Benzyl (2S,4S)-2-(tert-butyl)-4-(2-(2-chlorophenyl)-2-oxoethyl)-5-oxooxazolidine-3-carboxylate (12). Synthesized following GP-A using 2-chlorobenzoic acid (117.4 mg, 0.75 mmol, 1.5 equiv.).…”

“…In addition, α-keto acids are not readily available, and their synthesis often requires the use of hazardous reagents, such SeO 2 . Since II is a highly versatile species, we became interested in developing alternative methodologies for its synthesis using more readily available starting materials …”