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. 2024 Aug 1;28(8):3197-3205.
doi: 10.1021/acs.oprd.4c00101. eCollection 2024 Aug 16.

Synthetic Process Development of (R)-(+)-1,2-Epoxy-5-hexene: An Important Chiral Building Block

Daryl Guthrie  1 , John M Saathoff  1 , Rajkumar Lalji Sahani  1 , Aline Nunes De Souza  1 , Daniel W Cook  1 , Samuel R Hochstetler  1 , Justina M Burns  1 , Roudabeh Sadat Moazeni-Pourasil  1 , Janie Wierzbicki  1 , Saeed Ahmad  1 , G Michael Laidlaw  1 , B Frank Gupton  1 , Charles S Shanahan  1 , Douglas A Klumpp  1 , Limei Jin  1
Affiliations

Synthetic Process Development of (R)-(+)-1,2-Epoxy-5-hexene: An Important Chiral Building Block

Daryl Guthrie et al. Org Process Res Dev. .

Abstract

Herein, we describe two practical approaches to synthesize (R)-(+)-1,2-epoxy-5-hexene from inexpensive and readily available raw materials and reagents. The first approach is a two-step sequence, involving an epoxidation with meta-chloroperoxybenzoic acid (mCPBA) and a chiral resolution with (salen)Co(II), producing (R)-(+)-1,2-epoxy-5-hexene in 24-30% overall yield. The second approach utilizes readily available (R)-epichlorohydrin as the starting material and features an epoxide ring-opening reaction with allylMgCl and the NaOH-mediated ring closure reaction. Development of this two-step process affords R-(+)-1,2-epoxy-5-hexene in overall isolated yields of 55-60% with an exceptional purity profile. Both approaches have been successfully demonstrated on 100-200 g scales.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Reported Synthetic Route for the Synthesis of Compound 3 from Epoxide 1
Scheme 2
Scheme 2. Resolution Route for the Synthesis of Chiral Epoxide 1
Scheme 3
Scheme 3. Reported Method to Synthesize Chiral Epoxide 1 from Chiral Epichlorohydrin 6
See this image and copyright information in PMC

References

    1. Cleator E.; Sheen F. J.; Bio M. M.; Jos Brands K. M.; Davies A. J.; Dolling U.-H. Regioselective Synthesis of N-Substituted-4-Substituted Isothiazolidine-1,1-Dioxides. Tetrahedron Lett. 2006, 47 (25), 4245–4248. 10.1016/j.tetlet.2006.04.038. - DOI
    1. Cleator E.; Baxter C. A.; O’Hagan M.; O’Riordan T. J. C.; Sheen F. J.; Stewart G. W. Synthesis of Novel Benzoxathiazepine-1,1-Dioxides by Means of a One-Pot Multicomponent Reaction. Tetrahedron Lett. 2010, 51 (7), 1079–1082. 10.1016/j.tetlet.2009.12.099. - DOI
    1. Movassaghi M.; Jacobsen E. N. A Direct Method for the Conversion of Terminal Epoxides into γ-Butanolides. J. Am. Chem. Soc. 2002, 124 (11), 2456–2457. 10.1021/ja025604c. - DOI - PubMed
    1. Goodman S. N.; Jacobsen E. N. Enantiopure β-Hydroxy Morpholine Amides from Terminal Epoxides by Carbonylation at 1 Atm. Angew. Chem., Int. Ed. 2002, 41 (24), 4703–4705. 10.1002/anie.200290022. - DOI - PubMed
    1. Hoye T. R.; Eklov B. M.; Jeon J.; Khoroosi M. Sequencing of Three-Component Olefin Metatheses: Total Synthesis of Either (+)-Gigantecin or (+)-14-Deoxy-9-Oxygigantecin. Org. Lett. 2006, 8 (15), 3383–3386. 10.1021/ol061383u. - DOI - PubMed

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