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Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization

Nature Chemistry volume 7, pages 171–177 (2015)Cite this article

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A Corrigendum to this article was published on 19 February 2016

An Erratum to this article was published on 24 March 2015

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Abstract

5-Endo-trig cyclizations are generally considered to be kinetically unfavourable, as described by Baldwin's rules. Consequently, observation of this mode of reaction under kinetic control is rare. This is usually ascribed to challenges in achieving appropriate approach trajectories for orbital overlap in the transition state. Here, we describe a highly enantio- and diastereoselective route to complex indanes bearing all-carbon quaternary stereogenic centres via a 5-endo-trig cyclization catalysed by a chiral ammonium salt. Through computation, the preference for the formally disfavoured 5-endo-trig Michael reaction over the formally favoured 5-exo-trig Dieckmann reaction is shown to result from thermodynamic contributions to the innate selectivity of the nucleophilic group, which outweigh the importance of the approach trajectory as embodied by Baldwin's rules. Our experimental and theoretical findings demonstrate that geometric and stereoelectronic constraints may not be decisive in the observed outcome of irreversible ring-closing reactions.

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Figure 1: Formation of five-membered carbocycles.
Figure 2: Chemoselective derivatization of indane products.
Figure 3: Mechanistic possibilities and stereochemical model.
Figure 4: Computed free-energy profiles for ring closure.

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Change history

  • 19 February 2015

    In the version of this Article originally published Robert S. Paton (robert.paton@chem.ox.ac.uk) should have been acknowledged as a corresponding author.

  • 25 January 2016

    In the version of this Article originally published, the absolute stereochemistry of compounds in Fig.2 and Table 3 was reversed. Additionally, the absolute stereochemistry was reversed in the Markush product structure shown in the reaction scheme at the top of Table 2. These structures have been corrected in the online versions of the Article.

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Acknowledgements

The European Research Council provided financial support under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 259056. The authors thank Pfizer (D. Fradet), Novartis (T. Hunt), the EPSRC (to C.P.J. and K.E.J.), the Cambridge Trusts (to A.K.) and R. Driver for crystallography. The Ministry of Education and Science of Ukraine financed internships (S.I.O. and T.S.) at Oxford. The authors acknowledge Johnson-Matthey for a loan of Pd(PPh3)4. The authors acknowledge the use of the EPSRC UK National Service for Computational Chemistry Software (NSCCS) at Imperial College London and the Discovery Environment (XSEDE) supported by the National Science Foundation (grant no. OCI-1053575) in carrying out this work.

Author information

Authors and Affiliations

  1. Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK

    Craig P. Johnston, Abhishek Kothari, Kelvin E. Jackson, Robert S. Paton & Martin D. Smith

  2. Department of Chemistry, Dnipropetrovsk National University, Dnipropetrovsk, 49010, Ukraine

    Tetiana Sergeieva & Sergiy I. Okovytyy

Authors
  1. Craig P. Johnston
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Contributions

M.D.S. conceived and designed the study. C.P.J. and A.K. performed the synthetic experiments. R.S.P. conceived and designed the computational study. T.S., K.E.J. and S.I.O. performed the computational study. M.D.S., C.P.J. and R.S.P. co-wrote the paper.

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Correspondence to Robert S. Paton or Martin D. Smith.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 25055 kb)

Supplementary information

Crystallographic data for compound 16 (CIF 27 kb)

Supplementary information

Crystallographic data for compound 17 (CIF 43 kb)

Supplementary information

Crystallographic data for compound 28 (CIF 28 kb)

Supplementary information

Crystallographic data for compound anti-4 (CIF 23 kb)

Supplementary information

DFT optimized non-planar enolate 38 [(Z)-1,3-dimethoxy-2-(2-(3-methoxy-3-oxo-1-phenylprop-1-en-2-yl)phenyl)-1,3-dioxopropan-2-ide] (PDB 4 kb)

Supplementary information

DFT optimized Dieckmann product 39 [(Z)-3-benzylidene-2-methoxy-1,1-bis(methoxycarbonyl)-2,3-dihydro-1H-inden-2-olate] (PDB 4 kb)

Supplementary information

DFT optimized 40 [1,3,3-tris(methoxycarbonyl)-2-phenyl-2,3-dihydro-1H-inden-1-ide] (PDB 4 kb)

Supplementary information

DFT optimized planar enolate 41 [(Z)-2-methoxy-1-(2-(3-methoxy-3-oxo-1-phenylprop-1-en-2-yl)phenyl)-2-oxoethan-1-ide] (PDB 4 kb)

Supplementary information

DFT optimized TS: chiral ammonium phase-transfer catalysed (S)-1,3,3-tris(methoxycarbonyl)-2-phenyl-2,3-dihydro-1H-inden-1-ide (PDB 14 kb)

Supplementary information

DFT optimized TS: chiral ammonium phase-transfer catalysed (R)-1,3,3-tris(methoxycarbonyl)-2-phenyl-2,3-dihydro-1H-inden-1-ide (PDB 14 kb)

Supplementary information

DFT optimization: dimethyl (Z)-2-(1-methoxy-1-(l1-oxidanyl)-3-phenylallyl)malonate (PDB 3 kb)

Supplementary information

DFT optimization: (Z)-1,5-dimethoxy-4-(methoxycarbonyl)-5-oxo-3-phenylpent-1-en-1-olate (PDB 3 kb)

Supplementary information

DFT optimization: (Z)-3,5-dimethoxy-5-oxo-1-phenylpent-1-en-3-olate (PDB 3 kb)

Supplementary information

DFT optimization: (Z)-1,5-dimethoxy-5-oxo-3-phenylpent-1-en-1-olate (PDB 3 kb)

Supplementary information

DFT optimized TS 1 [(Z)-3-benzylidene-2-methoxy-1,1-bis(methoxycarbonyl)-2,3-dihydro-1H-inden-2-olate] (PDB 4 kb)

Supplementary information

DFT optimized TS 2 [1,3,3-tris(methoxycarbonyl)-2-phenyl-2,3-dihydro-1H-inden-1-ide] (PDB 4 kb)

Supplementary information

DFT optimized TS 3 [(Z)-1-benzylidene-2-methoxy-3-(methoxycarbonyl)-2,3-dihydro-1H-inden-2-olate] (PDB 4 kb)

Supplementary information

DFT optimized TS 4 [1,3-bis(methoxycarbonyl)-2-phenyl-2,3-dihydro-1H-inden-1-ide] (PDB 4 kb)

Supplementary information

DFT optimized TS: cyclization of cyclopentanide (PDB 1 kb)

Supplementary information

DFT optimized TS: cyclization of cyclopent-2-en-1-ide (PDB 1 kb)

Supplementary information

DFT optimized TS: cyclization of 2,3-dihydro-1H-inden-1-ide (PDB 1 kb)

Supplementary information

DFT optimized cis -43 [(2S,3S)-1,3-bis(methoxycarbonyl)-2-phenyl-2,3-dihydro-1H-inden-1-ide] (PDB 4 kb)

Supplementary information

DFT optimized trans -42 [(2R,3S)-1-((Z)-benzylidene)-2-methoxy-3-(methoxycarbonyl)-2,3-dihydro-1H-inden-2-olate] (PDB 4 kb)

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Johnston, C., Kothari, A., Sergeieva, T. et al. Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization. Nature Chem 7, 171–177 (2015). https://doi.org/10.1038/nchem.2150

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