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. 2018 May 18;83(10):5650-5664.
doi: 10.1021/acs.joc.8b00640. Epub 2018 May 2.

Desymmetrization of Cyclopropenes via the Potassium-Templated Diastereoselective 7- exo- trig Cycloaddition of Tethered Amino Alcohols toward Enantiopure Cyclopropane-Fused Oxazepanones with Antimycobacterial Activity

Vladimir A Maslivetc  1 , Danielle N Turner  2 , Kimberly N McNair  2 , Liliya Frolova  2 , Snezna Rogelj  2 , Anna A Maslivetc  1 , Nicolai A Aksenov  3 , Marina Rubina  1 , Michael Rubin  1   3
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Desymmetrization of Cyclopropenes via the Potassium-Templated Diastereoselective 7- exo- trig Cycloaddition of Tethered Amino Alcohols toward Enantiopure Cyclopropane-Fused Oxazepanones with Antimycobacterial Activity

Vladimir A Maslivetc et al. J Org Chem. .

Abstract

A strain-release-driven, cation-templated intramolecular nucleophilic addition of tethered alkoxides to prochiral cyclopropenes is described. Employment of chiral β- and γ-amino alkoxides allowed for highly diastereoselective assembly of a small series of enantiopure cyclopropane-fused oxazepanones. It was shown that the chiral center at C-4 plays a crucial role in controlling desymmetrization of the cyclopropenyl moiety, instigated by a profound potassium-templated effect. The preliminary biological activities of the new cyclopropane-fused medium heterocycles against Gram-positive bacteria, Gram-negative bacteria, mycobacteria, cancer cells, and fungus were evaluated.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Structures and yields of racemic cyclization products 17. Yields of purified materials are provided.
Figure 2.
Figure 2.
Structures and yields of enantiopure cyclization products 19. Yields of purified materials are provided.
Figure 3.
Figure 3.
Structures and yields of chiral cyclization products 25 and 28. Yields of purified materials are provided.
Scheme 1
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Scheme 11
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References

    1. For recent reviews, see:

    2. Edwards A; Rubina M; Rubin M Nucleophilic Addition of Cyclopropenes. Curr. Org. Chem 2016, 20, 1862–1877.
    3. Vicente R Recent Progresses towards the Strengthening of Cyclopropene Chemistry. Synthesis 2016, 48, 2343–2360.
    4. Zhu Z-B; Wei Y; Shi M Recent Developments of Cyclopropene Chemistry. Chem. Soc. Rev 2011, 40, 5534–5563. - PubMed

    1. See, for example:

    2. Zhang M; Guo J; Gong Y Highly Regioselective Cascade Formal Nucleophilic Substitution and Aldol Condensation of 2-Aroyl-1-chlorocyclopropanecarboxylic Esters. Eur. J. Org. Chem 2014, 2014, 1942–1950.
    3. Zhang M; Luo F; Gong Y Stereoselective Cascade Formal Nucleophilic Substitution and Mannich Reaction of Ethyl 2-Aroyl-1-chlorocyclopropanecarboxylates. J. Org. Chem 2014, 79, 1335–1343. - PubMed
    4. Hu J; Zhang M; Gong Y Cycloaddition Reactions of Alkyl Cyclopropenecarboxylates Generated in situ with Nitrones: Construction of Substituted Pyrroles and 1,2-Oxazinanes. Eur. J. Org. Chem 2015, 2015, 1970–1978.

    1. See, for example:

    2. Shavrin KN; Gvozdev VD; Budanov DV; Yurov SV; Nefedov OM 1-(Alk-1-ynyl)cyclopropenes: Synthesis by Interaction of 1-(Alk-1-ynyl)-1-halocyclopropanes with Lithium N,N-Dialkylamides and Subsequent Additions of the Latter. Mendeleev Commun 2006, 16, 73–76.
    3. Huang Z; Hu J; Gong Y Formation and Aromatization of Strained Bicyclic Pyrazolidines via Tandem Reaction of Alkyl 2-Aroyl-1-chlorocyclopropanecarboxylates with Acylhydrazones. Org. Biomol. Chem 2015, 13, 8561–8566. - PubMed
    4. Zhu Y; Gong Y Construction of 2-Pyrone Skeleton via Domino Sequence between 2-Acyl-1-Chlorocyclopropanecarboxylate and Amines. J. Org. Chem 2015, 80, 490–498. - PubMed
    5. Shavrin KN; Gvozdev VD; Nefedov OM 5-Methylenehexahydropyrrolo [1,2-a]imidazoles and 6-Methyleneoctahydropyrrolo[1,2-a]pyrimidines in the Reactions of 1-(Alk-1-ynyl)-1-chlorocyclopropanes with Lithium Derivatives of 1,2- and 1,3-Diaminoalkanes. Mendeleev Commun. 2008, 18, 300–301.
    1. Shavrin KN; Gvozdev VD; Nefedov OM Reactions of 1-(Alk-1-ynyl)-1-chlorocyclopropanes with Arenethiols and Alkanethiols in Dimethyl Sulfoxide in the Presense of KOH. Russ. Chem. Bull 2009, 58, 2432–2436.
    1. Zhang M; Gong Y; Wang W A Two-Step Sequence to Ethyl α-Fluorocyclopropanecarboxylates Through MIRC Reaction of Ethyl Dichloroacetate and Highly Regioselective Fluorination. Eur. J. Org. Chem 2013, 2013, 7372–7381.

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