Enantioselective catalytic Strecker reaction on cyclic (Z)-aldimines in flow: reaction optimization and sustainability aspects

Journal of Flow Chemistry - Trang 1-14 - 2023
Antonella Ilenia Alfano1, Andrea Sorato2, Alessia Ciogli2, Heiko Lange3, Margherita Brindisi1
1SPOTS-Lab – Sustainable Pharmaceutical and Organic Technology and Synthesis Laboratory, Department of Pharmacy, University of Naples Federico II, Naples, Italy
2Department of Drug Chemistry and Technologies, “Sapienza” University of Rome, Rome, Italy
3VaLiCell Lab – Laboratory for the Valorisation of Lignocellulosics, Department of Earth and Environmental Sciences, University of Milano-Bicocca, Milan, Italy

Tóm tắt

Catalytic enantioselective Strecker reactions on an achiral substrate using sub-stoichiometric amounts of a chiral catalyst represent an evolving key strategy for the effective synthesis of α-amino nitriles. We herein disclosed the set-up of a flow-based methodology for enantioselective Strecker, employing ethyl cyanoformate as a relatively safe cyanide source, a cinchona-based catalyst, and methanol as additive. A thorough exploration of key parameters allowed the identification of the most efficient reagent mixing mode, the optimum solvent for the flow synthesis, minimum catalyst loading, additive, temperature, and residence time. The newly developed method allows straightforward reaction channeling towards the fast and complete formation of the α-amino nitrile products, thus reducing the yield drop due to indolenine degradation during long-lasting batch-wise reactions. Moreover, we herein provide preliminary hints for sustainability, by proposing a simple procedure for catalyst recycling, thus opening the way for further optimization of the proposed methodology.

Tài liệu tham khảo

Iyer MS, Gigstad KM, Namdev ND, Lipton M (1996) Asymmetric catalysis of the Strecker amino acid synthesis by a cyclic dipeptide. J Am Chem Soc 118:4910–4911. https://doi.org/10.1021/ja952686e Monteiro JL, Pieber B, Corea G, Kappe CO (2016) Continuous Synthesis of Hydantoins: Intensifying the Bucherer-Bergs Reaction. Synlett 27:83–87. https://doi.org/10.1055/s-0035-1560317 Masamba W (2021) Petasis vs. Strecker Amino Acid Synthesis: Convergence, Divergence and Opportunities in Organic Synthesis. Molecules 2:1707. https://doi.org/10.3390/molecules26061707 Ashe K, Fernandez-Garcia C, Corpinot MK, Coggins AJ, Bucar DK, Powner MW (2019) Selective prebiotic synthesis of phosphoroaminonitriles and aminothioamides in neutral water. Commun Chem 2:23. https://doi.org/10.1038/s42004-019-0124-5 Kouznetsov VV, Galvis CEP (2018) Strecker reaction and alpha-amino nitriles: Recent advances in their chemistry, synthesis, and biological properties. Tetrahedron 74:773–810. https://doi.org/10.1016/j.tet.2018.01.005 Cleaves HJ, Chalmers JH, Lazcano A, Miller SL, Bada JL (2008) A reassessment of prebiotic organic synthesis in neutral planetary atmospheres. Orig Life Evol Biosph 38:105–115. https://doi.org/10.1007/s11084-007-9120-3 Krishnamurthy R, Snieckus V (2017) Prebiotic Organic Chemistry and Chemical pre-Biology: Speaking to the Synthetic Organic Chemists. Synlett 28:27–29. https://doi.org/10.1055/s-0036-1589831 Parker ET, Zhou M, Burton AS, Glavin DP, Dworkin JP, Krishnamurthy R, Fernandez FM, Bada JL (2014) A plausible simultaneous synthesis of amino acids and simple peptides on the primordial Earth. Angew Chem Int Ed Engl 53:8132–8136. https://doi.org/10.1002/anie.201403683 Ohfune Y, Shinada T (2003) Asymmetric Strecker route toward the synthesis of biologically active alpha, alpha-disubstituted alpha-amino acids. Bull Chem Soc Jpn 76:1115–1129. https://doi.org/10.1246/bcsj.76.1115 Arai T, Takahashi K, Ishiguro K, Yazawa K (1980) Increased production of saframycin A and isolation of saframycin S. J Antibiot (Tokyo) 33:951–960. https://doi.org/10.7164/antibiotics.33.951 Fukuyama T, Yang L, Ajeck KL, Sachleben RA (1990) Total Synthesis of (+/-)-Saframycin-A. J Am Chem Soc 112:3712–3713. https://doi.org/10.1021/ja00165a095 Dong W, Liu W, Liao X, Guan B, Chen S, Liu Z (2011) Asymmetric total synthesis of (-)-saframycin A from L-tyrosine. J Org Chem 76:5363–5368 Martinez EJ, Owa T, Schreiber SL, Corey EJ (1999) Phthalascidin, a synthetic antitumor agent with potency and mode of action comparable to ecteinascidin 743. Proc Natl Acad Sci U S A 96:3496–3501. https://doi.org/10.1073/pnas.96.7.3496 Cuevas C, Perez M, Martin MJ, Chicharro JL, Fernandez-Rivas C, Flores M, Francesch A, Gallego P, Zarzuelo M, de La Calle F, Garcia J, Polanco C, Rodriguez I, Manzanares I (2000) Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B. Org Lett 2:2545–2548. https://doi.org/10.1021/ol0062502 Mendez LYV, Kouznetsov VV (2013) First Girgensohnine Analogs Prepared Through InCl3-catalyzed Strecker Reaction and their Bioprospection. Curr Org Synth 10:969–973. https://doi.org/10.2174/157017941006140206105449 Juillerat-Jeanneret L (2014) Dipeptidyl peptidase IV and its inhibitors: therapeutics for type 2 diabetes and what else? J Med Chem 57:2197–2212. https://doi.org/10.1021/jm400658e Scheen AJ (2015) A review of gliptins for 2014. Expert Opin Pharmacother 16:43–62. https://doi.org/10.1517/14656566.2015.978289 Wang LX, Shen JF, Tang Y, Chen Y, Wang W, Cai ZG, Du ZJ (2007) Synthetic improvements in the preparation of clopidogrel. Org Process Res Dev 11:487–489. https://doi.org/10.1021/op700025d Feldman PL, Brackeen MF (1990) A Novel Route to the 4-Anilido-4-(Methoxycarbonyl)Piperidine Class of Analgetics. J Org Chem 55:4207–4209. https://doi.org/10.1021/jo00300a047 Feldman PL, James MK, Brackeen MF, Bilotta JM, Schuster SV, Lahey AP, Lutz MW, Johnson MR, Leighton HJ (1991) Design, Synthesis, and Pharmacological Evaluation of Ultrashort-Acting to Long-Acting Opioid Analgesics. J Med Chem 34:2202–2208. https://doi.org/10.1021/jm00111a041 Walz AJ, Hsu FL (2014) Synthesis of 4-anilinopiperidine methyl esters, intermediates in the production of carfentanil, sufentanil, and remifentanil. Tetrahedron Lett 55:501–502. https://doi.org/10.1016/j.tetlet.2013.11.058 Arasappan A, Venkatraman S, Padilla AI, Wu WL, Meng T, Jin Y, Wong J, Prongay A, Girijavallabhan V, Njoroge FG (2007) Practical and efficient method for amino acid derivatives containing beta-quaternary center: application toward synthesis of hepatitis C virus NS3 serine protease inhibitors. Tetrahedron Lett 48:6343–6347. https://doi.org/10.1016/j.tetlet.2007.07.002 Zhang FG, Zhu XY, Li S, Nie J, Ma JA (2012) Highly enantioselective organocatalytic Strecker reaction of cyclic N-acyl trifluoromethylketimines: synthesis of anti-HIV drug DPC 083. Chem Commun (Camb) 48:11552–11554. https://doi.org/10.1039/C2CC36307K Stork G (1989) The Stereospecific Synthesis of Reserpine. Pure Appl Chem 61:439–442 Lounasmaa M, Miettinen J, Hanhinen P, Jokela R (1997) Short synthesis of (+/-)-hirsutine: Direct addition of dimethyl malonate anion to a 1,4-conjugate iminium salt of appropriate 3-ethylindolo[2,3-a]quinolizidine. Tetrahedron Lett 38:1455–1458. https://doi.org/10.1016/S0040-4039(97)00056-7 Goes AD, Ferroud C, Santamaria J (1995) Regioselective Single-Electron Transfer Photocatalytic Synthesis of 2-Cyano-3-Ethylidenepiperidines - New Route to the Total Synthesis of (+/-)-Cis-Eburnamonine. Tetrahedron Lett 36:2235–2238. https://doi.org/10.1016/0040-4039(95)00233-3 Najera C, Sansano JM (2007) Catalytic asymmetric synthesis of alpha-amino acids. Chem Rev 107:4584–4671. https://doi.org/10.1021/cr050580o Elango R, Ball RO (2009) Pencharz PB Amino acid requirements in humans: with a special emphasis on the metabolic availability of amino acids. Amino Acids 37(1):19–27. https://doi.org/10.1007/s00726-009-0234-y Wang J, Liu X, Feng X (2011) Asymmetric strecker reactions. Chem Rev 111:6947–6983. https://doi.org/10.1021/cr200057t Cai XH, Xie B (2014) Recent advances in asymmetric Strecker reactions. Arkivoc 205–248. https://doi.org/10.3998/ark.5550190.p008.487 Pan SC, List B (2008) The catalytic acylcyanation of imines. Chemistry-an Asian Journal 3:430–437. https://doi.org/10.1002/asia.200700327 Wunnemann S, Frohlich R, Hoppe D (2008) Asymmetric Strecker reaction of N-benzlhydrylimines utilising new tropos biphenyldiol-based ligands. Eur J Org Chem 2008:684–692. https://doi.org/10.1002/ejoc.200700763 Zuend SJ, Coughlin MP, Lalonde MP, Jacobsen EN (2009) Scaleable catalytic asymmetric Strecker syntheses of unnatural alpha-amino acids. Nature 461:968-U223. https://doi.org/10.1038/nature08484 Karimi B, Maleki A (2009) Catalytic asymmetric Strecker hydrocyanation of imines using Yb(OTf)(3)-pybox catalysts. Chem Commun 5180–5182. https://doi.org/10.1039/B908854G Hatano M, Hattori Y, Furuya Y, Ishihara K (2009) Chiral Lanthanum(III)-Binaphthyldisulfonate Complexes for Catalytic Enantioselective Strecker Reaction. Org Lett 11:2321–2324. https://doi.org/10.1021/ol900680f Seayad AM, Ramalingam B, Yoshinaga K, Nagata T, Chai CLL (2010) Highly Enantioselective Titanium-Catalyzed Cyanation of Imines at Room Temperature. Org Lett 12:264–267. https://doi.org/10.1021/ol902540h Kaur P, Pindi S, Wever W, Rajale T, Li GG (2010) Asymmetric catalytic Strecker reaction of N-phosphonyl imines with Et2AlCN using amino alcohols and BINOLs as catalysts. Chem Commun 46:4330–4332. https://doi.org/10.1039/C0CC00287A Kaur P, Pindi S, Wever W, Rajale T, Li GG (2010) Asymmetric Catalytic N-Phosphonyl Imine Chemistry: The Use of Primary Free Amino Acids and Et2AlCN for Asymmetric Catalytic Strecker Reaction. J Org Chem 75:5144–5150. https://doi.org/10.1021/jo100865q Chen YJ, Chen C (2008) Enantioselective Strecker-type reaction of phosphinoyl ketimines catalyzed by a chiral Zr-bipyridyldiol catalyst. Tetrahedron-Asymmetry 19:2201–2209. https://doi.org/10.1016/j.tetasy.2008.09.011 Enders D, Gottfried K, Raabe G (2010) Organocatalytic Enantioselective Strecker Synthesis of alpha-Quaternary alpha-Trifluoromethyl Amino Acids. Adv Synth Catal 352:3147–3152. https://doi.org/10.1002/adsc.201000666 Zhang GW, Zheng DH, Nie J, Wang T, Ma JA (2010) Bronsted acid-catalyzed efficient Strecker reaction of ketones, amines and trimethylsilyl cyanide. Org Biomol Chem 8:1399–1405. https://doi.org/10.1039/B924272D Liu YL, Shi TD, Zhou F, Zhao XL, Wang X, Zhou J (2011) Organocatalytic Asymmetric Strecker Reaction of Di- and Trifluoromethyl Ketoimines. Remarkable Fluorine Effect. Org Lett 13:3826–3829. https://doi.org/10.1021/ol201316z Sigman MS, Vachal P, Jacobsen EN (2000) A general catalyst for the asymmetric Strecker reaction. Angew Chem-Int Ed 39:1279–1281. https://doi.org/10.1002/(sici)1521-3773(20000403)39:7%3c1279::aid-anie1279%3e3.0.co;2-u Becker C, Hoben C, Kunz H (2007) Enantioselective organocatalysis of strecker and Mannich reactions based on carbohydrates. Adv Synth Catal 349:417–424. https://doi.org/10.1002/adsc.200600370 Kanemitsu T, Toyoshima E, Miyazaki M, Nagata K, Itoh T (2010) Asymmetric Acyl-Strecker Reaction Promoted by Novel Thiourea Organocatalyst. Heterocycles 81:2781–2792 Shao YD, Tian SK (2012) A highly enantioselective catalytic Strecker reaction of cyclic (Z)-aldimines. Chem Commun 48:4899–4901. https://doi.org/10.1039/C2CC31001E Suginome M, Yamamoto A, Ito Y (2002) Bis(dialkylamino)cyanoboranes: highly efficient reagents for the Strecker-type aminative cyanation of aldehydes and ketones. Chem Commun 1392–1393. https://doi.org/10.1039/B203645B Kobayashi S, Ishitani H (1999) Catalytic enantioselective addition to imines. Chem Rev 99:1069–1094. https://doi.org/10.1021/cr980414z Das B, Ramu R, Ravikanth B, Reddy KR (2006) Studies on novel synthetic methodologies, part 67. (Bromodimethyl)sulfonium bromide catalyzed one-pot synthesis of alpha-aminonitriles. Synthesis-Stuttgart 1419–1422. https://doi.org/10.1002/chin.200636084 Kobayashi S, Ishitani H, Ueno M (1997) Facile synthesis of alpha-amino nitriles using lanthanide triflate as a Lewis acid catalyst. Synlett 115–116. https://doi.org/10.1002/chin.199723087 Heydari A, Arefi A, Khaksar S, Shiroodi RK (2007) Guanidine hydrochloride: An active and simple catalyst for Strecker type reaction. J Mol Catalys a-Chem 271:142–144. https://doi.org/10.1016/j.molcata.2007.02.046 Yadav JS, Reddy BVS, Eshwaraiah B, Srinivas M, Vishnumurthy P (2003) Three-component coupling reactions in ionic liquids: a facile synthesis of alpha-aminonitriles. New J Chem 27:462–465. https://doi.org/10.1039/B208844B Mojtahedi MM, Abaee MS, Abbasi H (2006) Environmentally friendly room temperature Strecker reaction: One-pot synthesis of alpha-aminonitriles in ionic liquid. J Iran Chem Soc 3:93–97. https://doi.org/10.1007/BF03245797 Martinez R, Ramon DJ, Yus M (2005) Catalyst-free multicomponent Strecker reaction in acetonitrile. Tetrahedron Lett 46:8471–8474. https://doi.org/10.1016/j.tetlet.2005.10.020 Matsumoto K, Kim JC, Iida H, Hamana H, Kumamoto K, Kotsuki H, Jenner G (2005) Multicomponent Strecker reaction under high pressure. Helv Chim Acta 88:1734–1753. https://doi.org/10.1002/hlca.200590136 Atherton JH, Blacker J, Crampton MR, Grosjean C (2004) The Strecker reaction: kinetic and equilibrium studies of cyanide addition to iminium ions. Org Biomol Chem 2:2567–2571. https://doi.org/10.1039/B407853E Wiles C, Watts P (2008) Evaluation of the Heterogeneously Catalyzed Strecker Reaction Conducted Under Continuous Flow. Eur J Org Chem 2008:5597–5613. https://doi.org/10.1002/ejoc.200800751 Ushakov DB, Gilmore K, Kopetzki D, McQuade DT, Seeberger PH (2014) Continuous-Flow Oxidative Cyanation of Primary and Secondary Amines Using Singlet Oxygen. Angew Chem-Int Ed 53:557–561. https://doi.org/10.1002/anie.201307778 Seayad AM, Ramalingam B, Chai CLL, Li CZ, Garland MV, Yoshinaga K (2012) Self-Supported Chiral Titanium Cluster (SCTC) as a Robust Catalyst for the Asymmetric Cyanation of Imines under Batch and Continuous Flow at Room Temperature. Chem-a Eur J 18:5693–5700. https://doi.org/10.1002/chem.201200528 Alfano AI, Brindisi M, Lange H (2021) Flow synthesis approaches to privileged scaffolds - recent routes reviewed for green and sustainable aspects. Green Chem 23:2233–2292. https://doi.org/10.1039/D0GC03883K Alfano AI, Zampella A, Novellino E, Brindisi M, Lange H (2020) Harnessing interrupted Fischer in continuous flow: sustainable synthesis of (spiro)indolenine and (spiro)indoline privileged scaffolds. React Chem Eng 5:2091–2100. https://doi.org/10.1039/D0RE00329H Alfano AI, Buommino E, Ferraro MG, Irace C, Zampella A, Lange H, Brindisi M (2021) Coupling Interrupted Fischer and Multicomponent Joullie-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics. ChemMedChem 16:3795–3809. https://doi.org/10.1002/cmdc.202100474 Porcheddu A, Mocci R, Brindisi M, Cuccu F, Fattuoni C, Delogu F, Colacino E, D’Auria MV (2022) Mechanochemical Fischer indolisation: an eco-friendly design for a timeless reaction. Green Chem 24:4859–4869. https://doi.org/10.1039/D2GC00724J Carlone A, Bernardi L, McCormack P, Warr T, Oruganti S, Cobley CJ (2021) Asymmetric Organocatalysis and Continuous Chemistry for an Efficient and Cost-Competitive Process to Pregabalin. Org Process Res Dev 25:2795–2805. https://doi.org/10.1021/acs.oprd.1c00394 Saeed A, Larik FA, Jabeen F, Mehfooz H, Ghumro SA, El-Seedi HR, Ali M, Channar PA, Ashra H (2018) Synthesis, Antibacterial and Antileishmanial Activity, Cytotoxicity, and Molecular Docking of New Heteroleptic Copper(I) Complexes with Thiourea Ligands and Triphenylphosphine. Russ J Gen Chem 88:541–550. https://doi.org/10.1134/S1070363218030246