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. 2018 Apr 18;140(15):4986-4990.
doi: 10.1021/jacs.8b00821. Epub 2018 Apr 5.

Stereospecific Ring Contraction of Bromocycloheptenes through Dyotropic Rearrangements via Nonclassical Carbocation-Anion Pairs

Shermin S Goh  1 , Pier Alexandre Champagne  2 , Sureshbabu Guduguntla  1 , Takashi Kikuchi  3   4 , Makoto Fujita  3 , K N Houk  2 , Ben L Feringa  1
Affiliations

Stereospecific Ring Contraction of Bromocycloheptenes through Dyotropic Rearrangements via Nonclassical Carbocation-Anion Pairs

Shermin S Goh et al. J Am Chem Soc. .

Abstract

Experimental and theoretical evidence is reported for a rare type I dyotropic rearrangement involving a [1,2]-alkene shift, leading to the regio- and stereospecific ring contraction of bromocycloheptenes. This reaction occurs under mild conditions, with or without a Lewis acid catalyst. DFT calculations show that the reaction proceeds through a nonclassical carbocation-anion pair, which is crucial for the low activation barrier and enantiospecificity. The chiral cyclopropylcarbinyl cation may be a transition state or an intermediate, depending on the reaction conditions.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Desymmetrization of 1 by AAS and Subsequent Rearrangement of Cycloheptenes 2 to Cyclohexenes 3,
Isolated yields over two steps. er’s of 2a–e and 3a–e were determined by chiral GC to be the same, so es is >99%.
Figure 1
Figure 1
Ball-and-stick representation of the X-ray structure of 3d determined by the crystalline sponge method.
Scheme 2
Scheme 2. Uncatalyzed Concerted Type I Dyotropic Rearrangements Occurring on a Static C–C Scaffold
Figure 2
Figure 2
Left: (a) 1H NMR spectroscopic profiles of bromocycloheptene 2d with ZnBr2 (1 equiv) in chloroform-d with increasing time; reaction scheme is shown at top. Right: Reaction progress of 2d with silica (500% w/w) monitored by timed aliquots in (b) chloroform-d and (c) benzene-d6. Reaction progress of 2d monitored by in situ NMR spectroscopy with (d) ZnBr2 (1 equiv) in chloroform-d and (e) TMSOTf (0.5 equiv) in chloroform-d.
Figure 3
Figure 3
Calculated free energy profile for the concerted dyotropic rearrangements from the pseudoaxial (left part) or pseudoequatorial (right part) conformations of 2a.
Figure 4
Figure 4
Calculated free energy profile for the stepwise transformation of 2a to 3a, catalyzed by ZnBr2. For the structure of 6a·ZnBr3, the ZnBr3– is hidden for clarity.
Figure 5
Figure 5
Lowest-energy pathway for racemization of 6a·ZnBr3. Free energies (kcal/mol) are relative to 2a·ZnBr2 (Figure 4). The ZnBr3– anions are hidden for clarity.
See this image and copyright information in PMC

References

    1. Desymmetrization of meso-dibromocycloalkenes with organolithium reagents: unpublished manuscript.

    1. For reviews of Cu-catalyzed AAS, see:

    2. Geurts K.; Fletcher S. P.; van Zijl A. W.; Minnaard A. J.; Feringa B. L. Pure Appl. Chem. 2008, 80, 1025–1037. 10.1351/pac200880051025. - DOI
    3. Harutyunyan S. R.; den Hartog T.; Geurts K.; Minnaard A. J.; Feringa B. L. Chem. Rev. 2008, 108, 2824–2852. 10.1021/cr068424k. - DOI - PubMed
    4. Alexakis A.; Bäckvall J. E.; Krause N.; Pàmies O.; Diéguez M. Chem. Rev. 2008, 108, 2796.10.1021/cr0683515. - DOI - PubMed
    5. Langlois J.-B.; Alexakis A. In Transition Metal Catalyzed Allylic Substitution in Organic Synthesis; Kazmaier U., Ed.; Springer-Verlag: Berlin, 2012; pp 235–268.
    6. Hornillos V.; Gualtierotti J.-B.; Feringa B. L. Top. Organomet. Chem. 2016, 58, 1–39. 10.1007/3418_2015_165. - DOI
    7. Baslé O.; Denicourt-Nowicki A.; Crévisy C.; Mauduit M. In Copper-Catalyzed Asymmetric Synthesis; Alexakis A., Krause N., Woodward S., Eds.; Wiley-VCH: Weinheim, 2014; pp 85–126.

    1. For selected examples of asymmetric allylic substitution with organolithium reagents, see:

    2. Pérez M.; Fañanás-Mastral M.; Bos P. H.; Rudolph A.; Harutyunyan S. R.; Feringa B. L. Nat. Chem. 2011, 3, 377.10.1038/nchem.1009. - DOI - PubMed
    3. Fañanás-Mastral M.; Pérez M.; Bos P. H.; Rudolph A.; Harutyunyan S. R.; Feringa B. L. Angew. Chem., Int. Ed. 2012, 51, 1922.10.1002/anie.201107840. - DOI - PubMed
    4. Guduguntla S.; Gualtierotti J.-B.; Goh S. S.; Feringa B. L. ACS Catal. 2016, 6, 6591.10.1021/acscatal.6b01681. - DOI
    5. Hornillos V.; Guduguntla S.; Fañanás-Mastral M.; Pérez M.; Bos P. H.; Rudolph A.; Harutyunyan S. R.; Feringa B. L. Nat. Protoc. 2017, 12, 493.10.1038/nprot.2016.179. - DOI - PubMed

    1. CCDC 1571256 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre.

    1. For selected examples of crystalline sponge X-ray crystallography, see:

    2. Inokuma Y.; Yoshioka S.; Ariyoshi J.; Arai T.; Hitora Y.; Takada K.; Matsunaga S.; Rissanen K.; Fujita M. Nature 2013, 495, 461.10.1038/nature11990. - DOI - PubMed
    3. Inokuma Y.; Yoshioka S.; Ariyoshi J.; Arai T.; Fujita M. Nat. Protoc. 2014, 9, 246.10.1038/nprot.2014.007. - DOI - PubMed
    4. Hoshino M.; Khutia A.; Xing H.; Inokuma Y.; Fujita M. IUCrJ 2016, 3, 139.10.1107/S2052252515024379. - DOI - PMC - PubMed

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