Ring-expansion reactions of Cyrene and derivatives with ethyl diazoacetate

Johannes Puschnig; Oscar Lamb; Christopher J. Sumby; Ben W. Greatrex

doi:10.1071/CH24163

RESEARCH ARTICLE (Open Access)

Previous Next Contents Vol 78(5)

Ring-expansion reactions of Cyrene and derivatives with ethyl diazoacetate

Johannes Puschnig ^A , Oscar Lamb ^A , Christopher J. Sumby ^B and Ben W. Greatrex

^A ^*

+ Author Affiliations

- Author Affiliations

^A Faculty of Medicine and Health, University of New England, Armidale, NSW 2351, Australia.

^B Department of Chemistry and the Centre for Advanced Nanomaterials, School of Physics, Chemistry and Earth Sciences, The University of Adelaide, Adelaide, SA 5005, Australia.

^* Correspondence to: ben.greatrex@une.edu.au

Handling Editor: Anastasios Polyzos

Australian Journal of Chemistry 78, CH24163 https://doi.org/10.1071/CH24163

Submitted: 7 November 2024 Accepted: 30 March 2025 Published online: 12 May 2025

© 2025 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC)

Abstract

The ring expansion and homologation of the biomass derivative Cyrene (6,8-dioxabicyclo[3.2.1]octan-4-one) has been developed by Lewis-acid promoted reactions with ethyl diazoacetate. Insertion into the C3–C4 bond gave a ring-expanded β-ketoester regioisomer as an equilibrating mixture of diastereomers, which was subjected to a one-pot hydrolysis and decarboxylation to give the 7,9-dioxabicyclo[4.2.1]nonan-5-one system (homocyrene). The reactivity of homocyrene was then investigated in a series of transformations known for the parent 6,8-dioxabicyclo[3.2.1]octan-4-one system, including the Baeyer–Villiger oxidation affording S-6-(hydroxymethyl)pyran-2-one, which has been used for the synthesis of jasmine lactone, and another one-carbon ring expansion. The ring-expansion process for Cyrene could be used to prepare chiral C₆ and C₇ synthons on scale from biomass.

Keywords: carbene, cyrene, diazo compounds, Jasmine lactone, levoglucosenone, organic green chemistry, ring expansion, valerolactone.

References

1 Ebata T, Matsushita H. Levoglucosenone: old but new optically active starting material. J Syn Org Chem Jpn 1994; 52: 1074-1082.
| Crossref | Google Scholar |

2 Camp JE. Bio‐available solvent cyrene: synthesis, derivatization, and applications. ChemSusChem 2018; 11: 3048-3055.
| Crossref | Google Scholar | PubMed |

3 Camp JE, Greatrex BW. Levoglucosenone: bio-based platform for drug discovery. Front Chem 2022; 10: 902239.
| Crossref | Google Scholar | PubMed |

4 Comba MB, Tsai Yh, Sarotti AM, Mangione MI, Suárez AG, Spanevello RA. Levoglucosenone and its new applications: valorization of cellulose residues. Eur J Org Chem 2018; 2018: 590-604.
| Crossref | Google Scholar |

5 Pacheco CM, Lima W, Lima FA, Gomez M, da Silva IG, Miranda L, Esteves PM, Itabaiana I, Jr, Wojcieszak R, Leão R, de Souza R. Levoglucosenone as a starting material for cascade continuous-flow synthesis of (R)-γ-carboxy-γ-butyrolactone. RSC Adv 2024; 14: 34611-34619.
| Crossref | Google Scholar | PubMed |

6 Sarotti AM, Spanevello RA, Suárez AG, Echeverría GA, Piro OE. 1,3-Dipolar cycloaddition reactions of azomethine ylides with a cellulose-derived chiral enone. A novel route for organocatalysts development. Org Lett 2012; 14: 2556-2559.
| Crossref | Google Scholar | PubMed |

7 Martínez S, Carrau G, Gonzalez D, Veiga N. Diels–Alder reaction of levoglucosenone with a protected cis-cyclohexadienediol: structural and electronic basis behind the unexpected stereoselectivity. ChemistrySelect 2017; 2: 11223-11230.
| Crossref | Google Scholar |

8 Nishikawa T, Asai M, Ohyabu N, Yamamoto N, Fukuda Y, Isobe M. Synthesis of a common key intermediate for (−)-tetrodotoxin and its analogs. Tetrahedron 2001; 57: 3875-3883.
| Crossref | Google Scholar |

9 Okano K, Ebata T, Koseki K, Kawakami H, Matsumoto K, Matsushita H. Formal synthesis of (+)-grandisol from levoglucosenone. Chem Pharm Bull 1993; 41: 861-865.
| Crossref | Google Scholar |

10 Koseki K, Ebata T, Kawakami H, Matsushita H, Itoh K, Naoi Y. Method of preparing (S)-gamma-hydroxymethyl-alpha, beta-butenolide. Eur Patent 0411403A1; European Patent Office; 1991.

11 Koseki K, Ebata T, Kawakami H, Matsushita H, Naoi Y, Itoh K. A method for easy preparation of optically pure (S)‐5‐hydroxy‐2‐penten‐4‐olide and (S)‐5‐hydroxypentan‐4‐olide. Heterocycles 1990; 31: 423-426.
| Crossref | Google Scholar |

12 Peru AAM, Flourat AL, Gunawan C, Raverty W, Jevric M, Greatrex BW, Alais F. Chemo-enzymatic synthesis of chiral epoxides ethyl and methyl (S)-3-(oxiran-2-yl)propanoates from renewable levoglucosenone: an access to enantiopure (S)-dairy lactone. Molecules 2016; 21: 988.
| Crossref | Google Scholar | PubMed |

13 Corey EJ, Pyne SG, Su W-g. Total synthesis of leukotriene B5. Tetrahedron Lett 1983; 24: 4883-4886.
| Crossref | Google Scholar |

14 Bińczak J, Dziuba K, Chrobok A. Recent developments in lactone monomers and polymer synthesis and application. Materials 2021; 14: 2881.
| Crossref | Google Scholar | PubMed |

15 Puschnig J, Greatrex BW. Ring‐expansion reactions of the biomass derivative cyrene via enamine dihalocyclopropanation. Eur J Org Chem 2024; 27: e202400031.
| Crossref | Google Scholar |

16 Shershnev I, Dar’in D, Chuprun S, Kantin G, Bakulina O, Krasavin M. The use of ∝-diazo-γ-butyrolactone in the Büchner–Curtius–Schlotterbeck reaction of cyclic ketones: a facile entry into spirocyclic scaffolds. Tetrahedron Lett 2019; 60: 1800-1802.
| Crossref | Google Scholar |

17 Gogula SS, Prasanna DV, Sridhar B, Lincoln CA, Reddy PM, Reddy BS. Sc(OTf) 3‐Catalyzed synthesis of 3‐substituted lawsones through a Buchner–Curtius–Schlotterbeck reaction. Eur J Org Chem 2024; 27: e202400362.
| Crossref | Google Scholar |

18 Kawai T, Isobe M, Peters SC. Factors affecting reaction of 1,6-anhydrohexos-2-ulose derivatives. Aust J Chem 1995; 48: 115-131.
| Crossref | Google Scholar |

19 Novikov RA, Rafikov RR, Shulishov EV, Konyushkin LD, Semenov VV, Tomilov YV. Reactions of levoglucosenone and its derivatives with diazo compounds. Russ Chem Bull 2009; 58: 327-334.
| Crossref | Google Scholar |

20 Rafikov RR, Novikov RA, Shulishov EV, Konyushkin LD, Semenov VV, Tomilov YV. Reaction of levoglucosenone with diazocyclopropane. Russ Chem Bull 2009; 58: 1927-1933.
| Crossref | Google Scholar |

21 Liu HJ, Majumdar SP. On the regioselectivity of boron trifluoride catalyzed ring expansion of cycloalkanones with ethyl diazoacetate. Synth Commun 1975; 5: 125-130.
| Crossref | Google Scholar |

22 Paterna R, André V, Duarte MT, Veiros LF, Candeias NR, Gois PM. Ring‐expansion reaction of isatins with ethyl diazoacetate catalyzed by dirhodium(II)/DBU metal–organic system: en route to viridicatin alkaloids. Eur J Org Chem 2013; 2013: 6280-6290.
| Crossref | Google Scholar |

23 Hashimoto T, Naganawa Y, Maruoka K. Desymmetrizing asymmetric ring expansion of cyclohexanones with α-diazoacetates catalyzed by chiral aluminum Lewis acid. J Am Chem Soc 2011; 133: 8834-8837.
| Crossref | Google Scholar | PubMed |

24 Dekker T, Harteveld JW, Wágner G, de Vries MCM, Custers H, van de Stolpe AC, de Esch IJP, Wijtmans M. Green drug discovery: novel fragment space from the biomass-derived molecule dihydrolevoglucosenone (Cyrene). Molecules 2023; 28: 1777.
| Crossref | Google Scholar | PubMed |

25 Cieplak AS. Stereochemistry of nucleophilic addition to cyclohexanone. The importance of two-electron stabilizing interactions. J Am Chem Soc 1981; 103: 4540-4552.
| Crossref | Google Scholar |

26 Milescu RA, Zhenova A, Vastano M, Gammons R, Lin S, Lau CH, Clark JH, McElroy CR, Pellis A. Polymer chemistry applications of Cyrene and its derivative Cygnet 0.0 as safer replacements for polar aprotic solvents. ChemSusChem 2021; 14: 3367-3381.
| Crossref | Google Scholar | PubMed |

27 Podversnik H, Camp JE, Greatrex BW. Practical and scalable enantioselective synthesis of (+)-majoranolide from Cyrene. Org Biomol Chem 2024; 22: 950-953.
| Crossref | Google Scholar | PubMed |

28 Ledingham ET, Stockton KP, Greatrex BW. Efficient synthesis of an indinavir precursor from biomass-derived (–)-levoglucosenone. Aust J Chem 2017; 70: 1146-1150.
| Crossref | Google Scholar |

29 Klepp J, Sumby CJ, Greatrex BW. Synthesis of a chiral auxiliary family from levoglucosenone and evaluation in the Diels–Alder reaction. Synlett 2018; 29: 1441-1446.
| Crossref | Google Scholar |

30 Houk KN, Jabbari A, Hall HK, Jr, Aleman C. Why δ-valerolactone polymerizes and γ-butyrolactone does not. J Org Chem 2008; 73: 2674-2678.
| Crossref | Google Scholar | PubMed |

31 Blaser F, Deschenaux P-F, Kallimopoulos T, Jacot-Guillarmod A. Synthèse des (−)-(6R)-et(+)-(6S)-tétrahydro-6-[(Z)-pent-2-ényl]-2H-pyran-2-one, lactones de Jasminum grandiflorum L. et de Polianthes tuberosa L. Helv Chim Acta 1991; 74: 787-790 [In French].
| Crossref | Google Scholar |

32 Mase N, Inoue A, Nishio M, Takabe K. Organocatalytic α-hydroxymethylation of cyclopentanone with aqueous formaldehyde: easy access to chiral δ-lactones. Bioorg Med Chem Lett 2009; 19: 3955-3958.
| Crossref | Google Scholar | PubMed |

33 Puschnig J, Lamb O, Greatrex B. Primary data for manuscript provisionally titled, ‘Ring-expansion reactions of Cyrene and derivatives with ethyl diazoacetate’. Zenodo 2024; 2024: version v1 [Dataset, published 7 November 2024].
| Crossref | Google Scholar |