α-Amino Acid Synthesis by 1,3-Nitrogen Migration: An Update

Abstract

An improved practical and efficient procedure for the synthesis of non-racemic unnatural α-amino acids through a stereocontrolled rearrangement is reported. Carboxylic acids are converted into azanyl esters RCO₂NHBoc followed by an iron-catalyzed 1,3-nitrogen migration to provide non-racemic α-amino acids in an asymmetric (α-monosubstituted α-amino acids) or enantioconvergent fashion (α,α-disubstituted α-amino acids). Under optimized conditions using a fluorinated chiral iron catalyst and 2,2,6,6-tetramethylpiperidine as the base in a solvent mixture of 1,2-dichlorobenzene and CHCl₃, enantioselectivities of up to 98% ee were obtained. Such high ee values are important for practical purposes, allowing the direct use of many of the obtained N-Boc-protected α-amino acids for subsequent applications.

Key words

α-amino acids - asymmetric catalysis - iron - C(sp³)−H amination - rearrangements

Publication History

Received: 28 March 2024

Accepted after revision: 03 May 2024

Article published online:
17 June 2024

• References


Reviews on applications of unnatural and non-proteinogenic α-amino acids:
• 1a Dougherty DA. Curr. Opin. Chem. Biol. 2000; 4: 645
• 1b Hodgson DR. W, Sanderson JM. Chem. Soc. Rev. 2004; 33: 422
• 1c Bhonsle JB, Clark T, Bartolotti L, Hicks RP. Curr. Top. Med. Chem. 2013; 13: 3205
• 1d Stevenazzi A, Marchini M, Sandrone G, Vergani B, Lattanzio M. Bioorg. Med. Chem. Lett. 2014; 24: 5349
• 1e Blaskovich MA. T. J. Med. Chem. 2016; 59: 10807
• 1f Agostini F, Völler J.-S, Koksch B, Acevedo-Rocha CG, Kubyshkin V, Budisa N. Angew. Chem. Int. Ed. 2017; 56: 9680
• 1g Henninot A, Collins JC, Nuss JM. J. Med. Chem. 2018; 61: 1382
• 1h Narancic T, Almahboub SA, O’Connor KE. World J. Microbiol. Biotechnol. 2019; 35: 67
• 1i Cheng Z, Kuru E, Sachdeva A, Vendrell M. Nat. Rev. Chem. 2020; 4, 275
• 1j Mei H, Han J, White S, Graham DJ, Izawa K, Sato T, Fustero S, Meanwell NA, Soloshonok VA. Chem. Eur. J. 2020; 26: 11349
• 1k Yokoo H, Hirano M, Misawa T, Demizu Y. ChemMedChem 2021; 16: 1226

Reviews on the synthesis of α-amino acids:
• 2a Williams RM, Hendrix JA. Chem. Rev. 1992; 92: 889
• 2b Ma J.-A. Angew. Chem. Int. Ed. 2003; 42: 4290
• 2c Maruoka K. Proc. Jpn. Acad., Ser. B 2003; 79: 181
• 2d Breuer M, Ditrich K, Habicher T, Hauer B, Keßeler M, Stürmer R, Zelinski T. Angew. Chem. Int. Ed. 2004; 43: 788
• 2e Nájera C, Sansano JM. Chem. Rev. 2007; 107: 4584
• 2f Kim Y, Park J, Kim M.-J. ChemCatChem 2011; 3: 271
• 2g Smith AM. R, Hii KK. Chem. Rev. 2011; 111: 1637
• 2h So SM, Kim H, Mui L, Chin J. Eur. J. Org. Chem. 2012; 229
• 2i D’Arrigo P, Cerioli L, Servi S, Viani F, Tessaro D. Catal. Sci. Technol. 2012; 2: 1606
• 2j Bera K, Namboothiri IN. N. Asian J. Org. Chem. 2014; 3: 1234
• 2k Metz AE, Kozlowski MC. J. Org. Chem. 2015; 80: 1
• 2l He G, Wang B, Nack WA, Chen G. Acc. Chem. Res. 2016; 49: 635
• 2m Xue Y.-P, Cao C.-H, Zheng Y.-G. Chem. Soc. Rev. 2018; 47: 1516
• 2n Moschner J, Stulberg V, Fernandes R, Huhmann S, Leppkes J, Koksch B. Chem. Rev. 2019; 119: 10718
• 2o Larionov VA, Stoletova NV, Maleev VI. Adv. Synth. Catal. 2020; 362: 4325
• 2p Ponra S, Boudet B, Phansavath P, Ratovelomanana-Vidal V. Synthesis 2021; 53: 193
• 2q Lin K, Shi A, Shi C, Lin J, Lin H. Front. Chem. 2021; 9: 687817

For recent examples on the asymmetric synthesis of α-amino acids, see:
• 3a Kang Q.-K, Selvakumar S, Maruoka K. Org. Lett. 2019; 21: 2294
• 3b Bendelsmith AJ, Kim SC, Wasa M, Roche SP, Jacobsen EN. J. Am. Chem. Soc. 2019; 141: 11414
• 3c Han J, Romoff TT, Moriwaki H, Konno H, Soloshonok VA. ACS Omega 2019; 4: 18942
• 3d Zou Y, Han J, Saghyan AS, Mkrtchyan AF, Konno H, Moriwaki H, Izawa K, Soloshonok VA. Molecules 2020; 25: 2739
• 3e Yang Z.-P, Freas DJ, Fu GC. J. Am. Chem. Soc. 2021; 143: 8614
• 3f Shatskiy A, Axelsson A, Stepanova EV, Liu J.-Q, Temerdashev AZ, Kore BP, Blomkvist B, Gardner JM, Dinér P, Kärkäs MD. Chem. Sci. 2021; 12: 5430
• 4 Ye C.-X, Shen X, Chen S, Meggers E. Nat. Chem. 2022; 14: 566
• 5 Zhou B, Ye C.-X, Meggers E. Eur. J. Org. Chem. 2023; e202300296
• 6 See also: Ye C.-X, Dansby DR, Chen S, Meggers E. Nat. Synth. 2023; 2: 645
• 7 For a recent review on metal-catalyzed enantioconvergent transformations, see: Yus M, Nájera C, Foubelo F, Sansano JM. Chem. Rev. 2023; 123: 11817
• 8 Arosio D, Caligiuri A, D’Arrigo P, Pedrocchi-Fantoni G, Rossi C, Saraceno C, Servi S, Tessaro D. Adv. Synth. Catal. 2007; 349: 1345
• 9 Ferraboschi P, Mieri MD, Galimberti F. Tetrahedron: Asymmetry 2010; 21: 2136
• 10 Evans DA, Dinsmore CJ, Evrard DA, DeVries KM. J. Am. Chem. Soc. 1993; 115: 6426