Application of Oxidative Ring Opening/Ring Closing by Reductive Amination Protocol for the Stereocontrolled Synthesis of Functionalized Azaheterocycles

Abstract

The current Account gives an insight into the synthesis of some N-heterocyclic β-amino acid derivatives and various functionalized saturated azaheterocycles accessed from substituted cycloalkenes via ring C=C bond oxidative cleavage followed by ring closing across double reductive amination. The ring-cleavage protocol has been accomplished according to two common approaches: a) Os-catalyzed dihydroxylation/NaIO₄ vicinal diol oxidation and b) ozonolysis. A comparative study on these methodologies has been investigated. Due to the everincreasing relevance of organofluorine chemistry in drug research as well as of the high biological potential of β-amino acid derivatives several illustrative examples to the access of various fluorine-containing piperidine or azepane β-amino acid derivatives are also presented in the current Account.

1 Introduction

2 Olefin-Bond Transformation by Oxidative Ring Cleavage

3 Synthesis of Saturated Azaheterocycles via Oxidative Ring-Opening/Ring-Closing Double Reductive Amination

3.1 Importance of Fluorine-Containing Azaheterocycles in Pharmaceutical Research

3.2 Synthesis of Azaheterocyclic Amino Acid Derivatives with a Piperidine or Azepane Framework through Oxidative Ring Opening/Reductive Amination

3.2.1 Synthesis of Piperidine β-Amino Esters

3.2.2 Synthesis of Azepane β-Amino Esters

3.2.3 Synthesis of Fluorine-Containing Piperidine γ-Amino Esters

3.3 Synthesis of Tetrahydroisoquinoline Derivatives through Oxidative Ring Opening/Reductive Amination Protocol

3.4 Synthesis of Functionalized Benzazepines through Reductive Amination

3.4.1 Synthesis of Benzo[c]azepines

3.4.2 Synthesis of Benzo[d]azepines

3.5 Synthesis of Various N-Heterocycles via Ozonolysis/Reductive Amination

3.5.1 Synthesis of Compounds with an Azepane Ring

3.5.2 Synthesis of Piperidine β-Amino Acids and Piperidine-Fused β-Lactams

3.5.3 Synthesis of γ-Lactams with a Piperidine Ring

3.5.4 Synthesis of other N-Heterocycles

4 Summary and Outlook

5 List of Abbreviations

Key words

azaheterocycles - ring opening - ring expansion - reductive amination - fluorine

Publication History

Received: 19 September 2021

Accepted after revision: 30 September 2021

Article published online:
03 November 2021

• References

• 1 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 2 Aniszewski T. Alkaloids. Chemistry, Biology, Ecology, and Applications, 2nd ed. Elsevier; Amsterdam: 2015
• 3 Tikhov RM, Kuznetsov NY. Org. Biomol. Chem. 2020; 18: 2793
• 4 Marcantoni E, Petrini M. Adv. Synth. Catal. 2016; 358: 3657
• 5 Huang H.-T, Lacy TC, Blachut B, Ortiz GX. Jr, Wang Q. Org. Lett. 2013; 15: 1818
• 6 Wu Y, Zhao Y, Wang H, Zhang F, Li R, Xiang J, Wang Z, Han B, Liu Z. Green Chem. 2020; 22: 3820
• 7 Zubkov IN, Romanov AR, Ushakov IA, Rulev AY. Tetrahedron 2020; 76: 130884
• 8 Rajput AP, Kankhare AR. Int. J. Pharm. Sci. Invent. 2017; 6: 19
• 9 Menaa F, Menaa B, Sharts ON. J. Mol. Pharm. Org. Process. Res. 2013; 1: 104
• 10 Hu X.-G, Hunter L. Beilstein J. Org. Chem. 2013; 9: 2696
• 11 Liu Q, Ni C, Hu J. Natl. Sci. Rev. 2017; 4 : 303
• 12 Punirun T, Soorukram D, Kuhakarn C, Reutrakul V, Pohmakotr M. J. Org. Chem. 2018; 83: 765
• 13 Furin GG, Zhuzhgov EL, Chi K.-V, Kim N.-A. Russ. J. Gen. Chem. 2005; 75: 394
• 14 Amii H, Nagaki A, Yoshida J.-I. Beilstein J. Org. Chem. 2013; 9: 2793
• 15 Gouverneur V, Seppelt K. Chem. Rev. 2015; 115: 563
• 16 Lewandowski G, Meissner E, Milchert E. J. Hazard. Mater. 2006; 136: 385
• 17 Chambers RD. Fluorine in Organic Chemistry Blackwell: Oxford, 2004. ; and references therein
• 18 Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, 2nd ed. Wiley-VCH; Weinheim: 2013
• 19 Uneyama K. Organofluorine Chemistry. Blackwell; Oxford: 2006. ; and references therein
• 20 Kiss L, Forró E, Fustero S, Fülöp F. Org. Biomol. Chem. 2011; 9: 6528
• 21 Nonn M, Kiss L, Haukka M, Fustero S, Fülöp F. Org. Lett. 2015; 17: 1074
• 22 Remete AM, Nonn M, Fustero S, Fülöp F, Kiss L. Molecules 2016; 21: 1493
• 23 Remete AM, Novák TT, Nonn M, Haukka M, Fülöp F, Kiss L. Beilstein J. Org. Chem. 2020; 16: 2562
• 24 Ábrahámi RA, Kiss L, Fustero S, Fülöp F. Synthesis 2017; 49: 1206
• 25 Remete AM, Nonn M, Fustero S, Haukka M, Fülöp F, Kiss L. Eur. J. Org. Chem. 2018; 3735
• 26 Remete AM, Nonn M, Fustero S, Haukka M, Fülöp F, Kiss L. Beilstein J. Org. Chem. 2017; 13: 2364
• 27a Malik G, Guinchard X, Crich D. Org. Lett. 2012; 14: 596
• 27b Kawaguchi M, Hayashi O, Sakai N, Hamada M, Yamamoto Y, Oda J. Agric. Biol. Chem. 1986; 50: 3107
• 27c Cully SJ, Storr TE, Rawling MJ, Abeysena IR, Hamza D, Jones G, Pearce CA, Quddus A, Lewis W, Stockman RA. Bioorg. Med. Chem. 2016; 24: 5249
• 27d Kuyasa S, Fisher TJ, Dusault PH. Synthesis 2011; 3475
• 27e Stoy P, Rush J, Pearson WH. Synth. Commun. 2004; 34: 3481
• 27f Yu W, Mei Y, Kang Y, Hua Z, Jin Z. Org. Lett. 2004; 6: 3217
• 28 Willand-Charnley R, Fisher TJ, Johnson BM, Dussault PH. Org. Lett. 2012; 14: 2242
• 29 Van Rheenen V, Kelly RC, Cha DY. Tetrahedron Lett. 1976; 1973
• 30 Wee AG, Liu B. Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons; Chichester: 2001. Oxidizing and Reducing Agents, 420
• 31 Carlsen PH. J, Katsuki T, Martin VS, Sharpless KB. J. Org. Chem. 1981; 46: 3936
• 32 Tao Z.-L, Zhang W.-Q, Chen D.-F, Adele A, Gong L.-Z. J. Am. Chem. Soc. 2013; 135: 9255
• 33 Rubin MB. Bull. Hist. Chem. 2001; 26: 40
• 34 Rubin MB. Helv. Chim. Acta 2003; 86: 930
• 35 Korshin EE, Bachi MD. Synthesis of Cyclic Peroxides, Vol. 2. John Wiley & Sons; Chichester: 2006: 723
• 36 Ornum SG. V, Champeau RM, Pariza R. Chem. Rev. 2006; 106: 2990
• 37 Criegee R. Angew. Chem., Int. Ed. Engl. 1975; 14: 745
• 38 Pappas JJ, Keaveney WP, Gancher E, Berger M. Tetrahedron Lett. 1966; 7: 4273
• 39 Chen L, Wiemer DF. J. Org. Chem. 2002; 67: 7561
• 40 O’Murchu C. Synthesis 1989; 880
• 41 Griesbaum K, Volpp W, Greinert R, Greunig HJ, Schmid J, Henke H. J. Org. Chem. 1989; 54: 383
• 42 Wrobleski A, Sahasrabudhe K, Aube J. J. Am. Chem. Soc. 2004; 126: 5475
• 43 White RW, King SW, O’Brien JL. Tetrahedron Lett. 1971; 3591
• 44 Neumeister J, Keul H, Saxena MP, Griesbaum K. Angew. Chem. 1978; 90: 999
• 45 Shiao H.-Y, Hsieh H.-P, Liao C.-C. Org. Lett. 2008; 10: 449
• 46 Phommart S, Sutthivaiyakit P, Chimnoi N, Ruchirawat S, Sutthivaiyakit S. J. Nat. Prod. 2005; 68: 927
• 47a Macías FA, Varela RM, Torres A, Oliva RM, Molinillo JM. G. Phytochemistry 1998; 48: 631
• 47b Macías FA, Lopez A, Varela RM, Torres A, Molinillo JM. G. Phytochemistry 2004; 65: 3057
• 48 Branan BM, Butcher JT, Olsen LR. J. Chem. Educ. 2007; 84: 1979
• 49 Kaur N, Wu F, Alom N.-E, Ariyarathna JP, Saluga SJ, Li W. Org. Biomol. Chem. 2019; 17: 1643
• 50 Bouyssi D, Monteiro N, Balme G. Beilstein J. Org. Chem. 2011; 7: 1387
• 51 Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845
• 52 Banfi L, Basso A, Lambruschini C, Moni L, Riva R. Chem. Heterocycl. Compd. 2017; 53: 382
• 53 Jevtić II, Došen-Mićović LI, Ivanović ER, Todorović NM, Ivanović MD. Synthesis 2017; 49: 3126
• 54 Cabré A, Verdaguer X, Riera A. Adv. Synth. Catal. 2019; 361: 4196
• 55 Guillaume M, Rioton S, Pardo DG, Cossy J. Org. Lett. 2018; 20: 5019
• 56 McMahon TC, Medina JM, Yang Y.-F, Simmons BJ, Houk KN, Garg NK. J. Am. Chem. Soc. 2015; 137: 4082
• 57 Vo C.-VT, Bode JW. J. Org. Chem. 2014; 79: 2809
• 58a Afanasyev OI, Kuchuk E, Usanov DL, Chusov D. Chem. Rev. 2019; 119: 11857
• 58b Caputo F, Cattaneo C, Clerici F, Gelmi ML, Pellegrino S. J. Org. Chem. 2006; 71: 8467
• 58c Blond A, Dockerty P, Álvarez R, Turcaud S, Lecourt T, Micouinm L. J. Org. Chem. 2013; 78: 12236
• 58d Guerra PG, Clerici P, Micouin L. J. Org. Chem. 2017; 82: 7689
• 59a Menczinger B, Nemes A, Szabó D, Schlosser G, Jernei T, Csámpai A, Rábai J. J. Fluorine Chem. 2020; 231: 109464
• 59b Furet P, Guagano V, Fairhurst RA, Weese PI, Bruce I, Knapp M, Fritsch C, Blasco F, Blanz J, Aichholz R, Hamon J, Fabbro D, Caravatti G. Bioorg. Med. Chem. Lett. 2013; 23: 3741
• 59c Rosenblum SB, Huynh T, Afonso A, Davis HR, Yumibe JN, Clader JW, Burnett DA. J. Med. Chem. 1998; 41: 973
• 59d Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong LT, Falgueyret JP, Kimmel DB, Lamontagne S, Léger S, LeRiche T, Li CS, Massé F, McKay DJ, Nicoll-Griffith DA, Oballa RM, Palmer JT, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Thérien M, Truong V.-L, Venuti MC, Wesolowski G, Young RN, Zamboni R, Black WC. Bioorg. Med. Chem. Lett. 2008; 18: 923
• 60 Reddy VP. Organofluorine Chemistry. Elsevier; Amsterdam: 2020
• 61 Remete AM, Kiss L. Eur. J. Org. Chem. 2019; 5572
• 62a Remete AM, Nonn M, Fustero S, Fülöp F, Kiss L. Tetrahedron 2018; 74: 6367
• 62b Han J, Kiss K, Mei H, Remete AM, Ponikvar-Svet M, Sedgwick DM, Roman R, Fustero S, Moriwaki H, Soloshonok VA. Chem. Rev. 2021; 121: 4678
• 63 Ojima I. J. Fluorine Chem. 2017; 198: 10
• 64 Cheng HG, Yin G. Chem 2019; 5: 1022
• 65 Mei H, Remete AM, Zou Y, Moriwaki H, Fustero S, Kiss L, Soloshonok VA, Han J. Chin. Chem. Lett. 2020; 31: 2401
• 66 Mei H, Han J, Fustero S, Medio-Simon M, Sedgwick DM, Santi C, Ruzziconi R, Soloshonok VA. Chem. Eur. J. 2019; 25: 11797
• 67 Benedek G, Palkó M, Wéber E, Martinek TA, Forró E, Fülöp F. Eur. J. Org. Chem. 2008; 3724
• 68a Cherepanova M, Kiss L, Fülöp F. Tetrahedron 2014; 70: 2515
• 68b Kiss L, Nonn M, Sillanpaa R, Haukka M, Fustero S, Fülöp F. Chem. Asian J. 2016; 11: 3376
• 69 Kiss L, Forró E, Fustero S, Fülöp F. Eur. J. Org. Chem. 2011; 4993
• 70 Ouchakour L, Ábrahámi RA, Forró E, Haukka M, Fülöp F, Kiss L. Eur. J. Org Chem. 2019; 2202
• 71 Nonn M, Remete AM, Kiss L. Helv. Chim. Acta 2020; 103: e2000090
• 72 Kiss L, Ouchakour L, Ábrahámi RA, Nonn M. Chem. Rec. 2020; 20: 120
• 73a Kiss L, Fülöp F. Chem. Rev. 2014; 114: 1116
• 73b Kiss L, Mándity IM, Fülöp F. Amino Acids 2017; 49: 1441
• 73c Omura S, Murata M, Imamura N, Iwai Y, Tanaka H. J. Antibiot. 1984; 1324
• 73d Yamashita M, Kawai Y, Uchida I, Komori T, Kohsaka M, Imanaka H, Sakane K, Setoi H, Teraji T. J. Antibiot. 1984; 1284
• 73e Hasenoehrl A., Galic T., Ergovic G., Marsic N., Skerlev M., Mittendorf J., Geschke U., Schmidt A., Schoenfeld W. Antimicrob Agents Chemother 2006, 50, 3011.
• 74 Ouchakour L, Nonn M, Kiss L. Fluorine Notes 2019; 122: 1
• 75 Nonn M, Kara D, Ouchakour L, Forró E, Haukka M, Kiss L. Synthesis 2021; 53: 1163
• 76 Ona I, José AO, Pau N, Rosa MO. Tetrahedron 2017; 73: 6286
• 77 Kudo F, Miyanaga A, Eguchi T. Nat. Prod. Rep. 2014; 31: 1056
• 78 Magriotis PA. Angew. Chem. Int. Ed. 2001; 40: 4377
• 79a Chang Z, Guillot R, Boddaert T, Aitken DJ. J. Org. Chem. 2019; 84: 10518
• 79b Fülöp F, Martinek TA. Chem. Soc. Rev. 2012; 41: 687
• 80 Ashfaq M, Tabassum R, Ahmad MM, Hassan NA, Oku H, Rivera G. Med. Chem. 2015; 5: 295
• 81 Kiss L, Kazi B, Forró E, Fülöp F. Tetrahedron Lett. 2008; 49: 339
• 82 Ábrahámi RA, Kiss L, Barrio P, Fülöp F. Tetrahedron 2016; 72: 7526
• 83 Kazi B, Kiss L, Forró E, Mándity I, Fülöp F. ARKIVOC 2010; (ix): 31
• 84 Kiss L, Cherepanova M, Forró E, Fülöp F. Chem. Eur. J. 2013; 19: 2102
• 85 Ngo D.-H, Vo TS. Molecules 2019; 24: 2678
• 86 Silverman RB. Angew. Chem. Int. Ed. 2008; 47: 3500
• 87a Singh R, Vince R. Chem. Rev. 2012; 112: 4642
• 87b Arjona O, Csaky AG, Plumet J. Eur. J. Org. Chem. 2003; 611
• 88 Forró E, Fülöp F. Eur. J. Org. Chem. 2008; 5263
• 89 Kiss L, Forró E, Sillanpää R, Fülöp F. Synthesis 2010; 153
• 90 Scott JD, Williams RM. Chem. Rev. 2002; 102: 1669
• 91 Shuyun J, Mingxin Q, Jing L, Gang X, Lirong Y, Jianping W. Green Chem. 2019; 21: 5579
• 92 Zhang Y, Fang H, Feng J, Jia Y, Wang X, Xu W. J. Med. Chem. 2011; 54: 5532
• 93 Chakka SK, Andersson PG, Maguire GE. M, Kruger HG, Govender T. Eur. J. Org. Chem. 2010; 972
• 94 Chrzanowska M, Grajewska A, Rozwadowska MD. Chem. Rev. 2016; 116: 12369
• 95 Ábrahámi RA, Fustero S, Fülöp F, Kiss L. Synlett 2018; 29: 2066
• 96 Gini A, Bamberger J, Luis-Barrera J, Zurro M, Mas-Ballesté R, Alemán J, Mancheño OG. Adv. Synth. Catal. 2016; 358: 4049
• 97 Pandey AK, Han SH, Mishra NK, Kang D, Lee SH, Chun R, Kim IS. ACS Catal. 2017; 8: 742
• 98 So M, Kotake T, Matsuura K, Inui M, Kamimura A. J. Org. Chem. 2012; 77: 4017
• 99 Ouchakour L, Nonn M, D’hooghe M, Kiss L. J. Fluorine Chem. 2020; 232: 109466
• 100 Bryan MC, Dillon B, Hamann LG, Hughes GJ, Kopach ME, Peterson EA, Pourashraf M, Raheem I, Richardson P, Richter D, Sneddon HF. J. Med. Chem. 2013; 56: 6007
• 101 McElroy CR, Constantinou A, Jones LC, Summerton L, Clark JH. Green Chem. 2015; 17: 3111
• 102 Bandichhor R, Bhattacharya A, Diorazio L, Dunn P, Fraunhoffer K, Gallou F, Hayler J, Hickey M, Hinkley B, Hughes D, Humphreys L, Kaptein B, Mathew S, Oh L, Richardson P, White T, Wuyts S. Org. Process Res. Dev. 2014; 18: 863
• 103 Marion P, Bernela B, Piccirilli A, Estrine B, Patouillard N, Guilbotf J, Jérôme F. Green Chem. 2017; 19: 4973
• 104 Ouchakour L, Nonn M, Remete AM, Kiss L. Eur. J. Org. Chem. 2021; 3874
• 105 Coldham I, Price KN, Rathmell RE. Org. Biomol. Chem. 2003; 1: 2111