Synlett 2015; 26(03): 350-351
DOI: 10.1055/s-0034-1379548
cluster
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Copper-Catalyzed Reductive Coupling of Vinylazaarenes with N-Boc Aldimines

Bonnie Choi
a  EaStCHEM, School of Chemistry, University of Edinburgh, Joseph Black Building, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, UK
b  School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK   Fax: +44(115)9513555   Email: hon.lam@nottingham.ac.uk
,
Aakarsh Saxena
a  EaStCHEM, School of Chemistry, University of Edinburgh, Joseph Black Building, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, UK
,
Joshua J. Smith
a  EaStCHEM, School of Chemistry, University of Edinburgh, Joseph Black Building, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, UK
b  School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK   Fax: +44(115)9513555   Email: hon.lam@nottingham.ac.uk
,
Gwydion H. Churchill
c  AstraZeneca Process Research and Development, Charter Way, Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, UK
,
Hon Wai Lam*
a  EaStCHEM, School of Chemistry, University of Edinburgh, Joseph Black Building, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, UK
b  School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK   Fax: +44(115)9513555   Email: hon.lam@nottingham.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 16 September 2014

Accepted after revision: 22 October 2014

Publication Date:
21 November 2014 (online)

Abstract

The diastereo- and enantioselective reductive coupling of vinylazaarenes with N-Boc aldimines is described. The reactions proceed using chiral copper–bisphosphine complexes in the presence of TMDS as a hydride source to give reductive coupling products in moderate to high enantioselectivities.

Supporting Information

 
  • References and Notes

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  • 9 General Procedure for the Reductive Coupling of Vinylazaarenes with Imine 2a Using Ligand L1A solution of the appropriate vinylazaarene (0.30 mmol), Cu(OAc)2·H2O (3.0 mg, 0.01 mmol), (S)-DTBM-SEGPHOS (L1, 17.7 mg, 0.015 mmol), and imine 2a (68 mg, 0.33 mmol) in THF (1.5 mL) was stirred at 0 °C for 15 min. TMDS (64 μL, 0.36 mmol) was then added dropwise over 1 min. The mixture was stirred at 0 °C for 1 h, then at r.t. for 15 h. The reaction was quenched carefully with SiO2, and the resulting suspension was stirred for 15 min before being filtered through a short plug of SiO2 using EtOAc as eluent and concentrated in vacuo. Purification of the residue by flash column chromatography gave the reductive coupling product.Data for 3a Rf = 0.31 (20% EtOAc–PE); mp 128–131 °C (EtOAc–PE); [α]D 24 +98.6 (c 1.10, CHCl3). IR (film): 2970, 2934, 1709 (C=O), 1503, 1390, 1289, 827, 756, 700 cm–1. 1H NMR [500 MHz, (CD3)2CO]: δ = 8.14 (d, J = 8.4 Hz, 1 H), 8.05 (d, J = 8.3 Hz, 1 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.75 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H), 7.57–7.51 (m, 1 H), 7.33 (d, J = 7.3 Hz, 2 H), 7.24 (t, J = 8.0 Hz, 3 H), 7.16 (t, J = 7.0 Hz, 2 H), 5.09 (t, J = 7.7 Hz, 1 H), 3.63–3.54 (m, 1 H), 1.35 (d, J = 6.9 Hz, 3 H), 1.27 (s, 9 H). 13C NMR [125.8 MHz, (CD3)2CO]: δ = 165.1, 156.0, 148.5, 144.1, 137.0, 130.2, 129.7, 128.9, 128.6, 128.0, 127.7, 127.5, 126.8, 122.8, 78.5, 60.2, 48.1, 28.5, 19.6. ESI-HRMS: m/z calcd for C23H27N2O2 [M + H]+: 363.2067; found: 363.2067. HPLC: Chiralcel OD-H column (i-hexane–i-PrOH, 90:10; 1.0 mL/min, 254 nm, 25 °C); t R (major) = 4.6 min, t R (minor) = 5.9 min; 85% ee.Data for 3f Rf = 0.32 (20% EtOAc–PE); mp 142–145 °C (EtOAc–PE); [α]D 24 +55.0 (c 1.00, CHCl3). IR (film): 2979, 2928, 1713 (C=O), 1498, 1390, 1365, 1170, 1022, 759, 700 cm–1. 1H NMR [400 MHz, (CD3)2CO]: δ = 7.98 (t, J = 8.9 Hz, 2 H), 7.54–7.45 (m, 1 H), 7.45–7.35 (m, 3 H), 7.30 (t, J = 7.4 Hz, 2 H), 7.23 (t, J = 7.5 Hz, 1 H), 6.80 (d, J = 7.5 Hz, 1 H), 5.15–4.90 (m, 1 H), 3.88–3.65 (m, 1 H), 1.37 (d, J = 6.8 Hz, 3 H), 1.28 (s, 9 H). 13C NMR [125.8 MHz, (CD3)2CO]: δ = 174.7, 155.9, 154.1, 142.9, 135.6, 129.1, 128.0, 127.8, 126.8, 125.7, 123.4, 122.6, 78.9, 60.3, 45.1, 28.5, 19.5. ESI-HRMS: m/z calcd for C21H25N2O2S [M + H]+: 369.1631; found: 369.1634. HPLC: Chiralpak IC column (hexane–i-PrOH, 98:2; 0.8 mL/min, 280 nm, 25 °C); t R (major) = 18.9 min, t R (minor) = 27.9 min; 88% ee.
  • 10 Where indicated, the relative and absolute stereochemistries of the products were assigned by analogy with those of products 3f,g, 4d,k,q,t, which were determined by X-ray crystallography (see Supporting Information for details). CCDC 1019731–1019736 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif or by writing to the ­Cambridge Crystallographic Data Centre, 12, Union Road, ­Cambridge CB2 1EZ, UK; fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk.