Total Synthesis of Citreochlorol Monochloro Analogues via a Catalytically Enantioselective Carbonyl Allylation

Abstract

An efficient synthetic route to citreochlorol analogues, halogenated polyketide secondary metabolites, is described. The key features are Krische’s enantioselective carbonyl allylation, IBr-promoted cyclization, and regioselective epoxide opening. The importance of the route lies in accessing a versatile epoxy ether that enables the formation of citreochlorol monochloro derivatives.

Key words

chlorinated natural products - polyketides - carbonyl allylation - citreochlorol - antibiotics

• References

• 1a Katz L. Chem. Rev. 1997; 97: 2557
• 1b Robertsen HL, Musiol-Kroll EM. Antibiotics 2019; 8: 157
• 2 Gribble GW. J. Chem. Educ. 2004; 81: 1441
• 3a Xu Z, Yang Z, Liu Y, Lu Y, Chen K, Zhu W. J. Chem. Inf. Model. 2014; 54: 69
• 3b Hernandes MZ, Cavalcanti SM. T, Moreira DR. M, Filgueira de Azevedo WJr, Leite AC. L. Curr. Drug Targets 2010; 11: 303
• 3c Gál B, Bucher C, Burns NZ. Mar. Drugs 2016; 14: 206
• 4 Yang MH, Li TX, Wang Y, Liu RH, Luo J, Kong LY. Fitoterapia 2017; 116: 72
• 5 Sunnapu R, Banoth SN, Reyno RS, Thomas A, Venugopal N, Rajendar G. J. Org. Chem. 2020; 85: 4103
• 6 Sunnapu R, Rajendar G. Eur. J. Org. Chem. 2021; 1637
• 7a Cai H, Guengerich FP. Chem. Res. Toxicol. 2000; 13: 327
• 7b Tabarelli G, Alberto EE, Deobald AM, Marin G, Rodrigues OE. D, Dornelles L, Braga AL. Tetrahedron Lett. 2010; 51: 5728
• 8 Tokuyama H, Yokoshima S, Yamashita T, Fukuyama T. Tetrahedron Lett. 1998; 39: 3189
• 9 Ranu BC, Majee A, Das AR. Tetrahedron Lett. 1996; 37: 1109
• 10 Fiandanese V, Marchese G, Martina V, Ronzini L. Tetrahedron Lett. 1984; 25: 4805
• 11 Inoue K, Shimizu Y, Shibata I, Baba A. Synlett 2001; 1659

Selected examples:
• 12a Cheung LL, Marumoto S, Anderson CD, Rychnovsky SD. Org. Lett. 2008; 10: 3101
• 12b Jana N, Nanda S. Eur. J. Org. Chem. 2012; 4313
• 12c Ahlers A, Haro T. d, Gabor B, Fürstner A. Angew. Chem. Int. Ed. 2016; 55: 1406
• 12d Ochiai K, Kuppusamy S, Yasui Y, Harada K, Gupta NR, Takahashi Y, Kubota T, Kobayashi J, Hayashi Y. Chem. Eur. J. 2016; 22: 3287
• 12e Jana N, Nanda S. Tetrahedron: Asymmetry 2012; 23: 802
• 12f Arai K, Buonamici S, Chan B, Corson L, Endo A, Gerard B, Hao M.-H, Karr C, Kira K, Lee L, Liu X, Lowe JT, Luo T, Marcaurelle LA, Mizui Y, Nevalainen M, O’Shea MW, Park ES, Perino SA, Prajapati S, Shan M, Smith PG, Tivitmahaisoon P, Wang JY, Warmuth M, Wu K.-M, Yu L, Zhang H, Zheng G.-Z, Keaney GF. Org. Lett. 2014; 16: 5560
• 12g Wender PA, Horan JC, Verma VA. Org. Lett. 2006; 8: 5299
• 12h Xu Z, Chen Z, Ye T. Tetrahedron: Asymmetry 2004; 15: 355
• 12i Yang M, Peng W, Guo Y, Ye T. Org. Lett. 2020; 22: 1776
• 12j Smith AB. III, Lin QY, Doughty VA, Zhuang LH, McBriar MD, Kerns JK, Boldi AM, Murase N, Moser WH, Brook CS, Bennett CS, Nakayama K, Sobukawa M, Trout RE. L. Tetrahedron 2009; 65: 6470
• 12k Trost BM, Dong G. J. Am. Chem. Soc. 2010; 132: 16403
• 12l Della-Felice F, Sarotti AM, Pilli RA. J. Org. Chem. 2017; 82: 9191
• 13 Kim IS, Ngai M.-Y, Krische MJ. J. Am. Chem. Soc. 2008; 130: 14891
• 14a Alam M, Wise C, Baxter CA, Cleator E, Walkinshaw A. Org. Process Res. Dev. 2012; 16: 435
• 14b Chen W, Xiong F, Liu Q, Xu L, Wu Y, Chen F. Tetrahedron 2015; 71: 4730
• 14c Yan X, Zhang S.-M, Wu Y, Gao P. Org. Biomol. Chem. 2011; 9: 6797
• 15a Mitsunobu O. Synthesis 1981; 1
• 15b Nesbitt CL, McErlean CS. P. Org. Biomol. Chem. 2011; 9: 2198
• 15c Dickmann D, Diekmann M, Holec C, Pietruszka J. Tetrahedron 2019; 75: 689
• 15d Pal P, Jana N, Nanda S. Org. Biomol. Chem. 2014; 12: 8257
• 16a Bartlett PA, Meadows JD, Brown EG, Morimoto A, Jernstedt KK. J. Org. Chem. 1982; 47: 4013
• 16b Duan JJ.-W, Smith AB. III. J. Org. Chem. 1993; 58: 3703
• 17a Bartoli G, Bosco M, Carlonr A, Dalpozzo R, Locatelli M, Melchiorre P, Palazzi P, Sambri L. Synlett 2006; 2104
• 17b Wu Y, Liu MJ, Huang HQ, Huang GX, Xiong FJ, Chen FE. Eur. J. Org. Chem. 2017; 3681
• 18a Tirado R, Prieto JA. J. Org. Chem. 1993; 58: 5666
• 18b Smith AB. III, Zhuang L, Brook CS, Lin Q, Moser WH, Trout RE. L, Boldi AM. Tetrahedron Lett. 1997; 38: 8671

We tried several chlorination methods, but only the combination of CCl₄ and Ph₃P worked in the system.
• 19a CCl₄/Ph₃P: Ishikawa T, Shimizu Y, Kudoh T, Saito S. Org. Lett. 2003; 5: 3879
• 19b NCS/Ph₃P: Kadayat TM, Lee G, Jung K, Hwang H.-J, Joo J, Hahn D, Hwang H, Park K.-G, Cho SJ, Kim K.-H, Chin J. Tetrahedron Lett. 2018; 59: 4384
• 19c PCl₃: Dibenedetto A, Angelini A, Aresta M, Ethiraj J, Fragale C, Nocito F. Tetrahedron 2011; 67: 1308
• 19d SOCl₂: Kurosawa W, Kan T, Fukuyama T. J. Am. Chem. Soc. 2003; 125: 8112
• 20 CCDC 2089679 (compound 5) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 21 Zhang M, Zhu L, Ma X. Tetrahedron: Asymmetry 2003; 14: 3447
• 22 McDonald FE, Wu M. Org. Lett. 2002; 4: 3979
• 23 Gannedi V, Ali A, Singh PP, Vishwakarma RA. J. Org. Chem. 2020; 85: 7757
• 24 Huckins JR, Vicente J. d, Rychnovsky SD. Org. Lett. 2007; 9: 4757
• 25 See the Supporting Information
• 26 Warmuth L, Weiß A, Reinhardt M, Meschkov A, Schepers U, Podlech J. Beilstein J. Org. Chem. 2021; 17: 224