Synlett 2017; 28(20): 2933-2935
DOI: 10.1055/s-0036-1589091
letter
© Georg Thieme Verlag Stuttgart · New York

Trapping of Hexadehydro-Diels–Alder Benzynes with Exocyclic, Conjugated Enals as a Route to Fused Spirocyclic Benzopyran Motifs

Tao Wang, Christian J. Oswood, Thomas R. Hoye*
  • Department of Chemistry, University of Minnesota, 207 Pleasant St., SE, Minneapolis, Minnesota 55455, USA   Email: hoye@umn.edu
Financial support for these studies was provided by the National Institute of General Medical Sciences (R01 GM108762) of the National Institutes of Health. NMR data were recorded, in part, using an instrument purchased through a NIH Shared Instrumentation Grant (S10OD011952).
Further Information

Publication History

Received: 13 June 2017

Accepted after revision: 11 July 2017

Publication Date:
22 August 2017 (eFirst)

Dedicated with very best wishes to Professor Victor Snieckus on the occasion of his 80th birthday

Abstract

Exocyclic, conjugated enals react with benzynes generated by heating various triyne-containing substrates to produce spirocyclic benzopyran derivatives. These products are consistent with a mechanistic sequence that involves initial net [2+2] cycloaddition of the benzyne and aldehyde followed by 4π-electrocyclic ring opening and 6π ring closing.

Supporting Information

 
  • References and Notes

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  • 8 NOE experiments carried out on this mixture of coeluting isomers (toluene-d 8, 90 °C) failed to reveal the relative configuration between the spirocyclic and methyl ester bearing stereocenters. In particular, the alkene protons enhanced one another in both diastereomers but neither showed a detectable enhancement of the pyrrolidine methine proton.
    • 9a Chen J. Palani V. Hoye TR. J. Am. Chem. Soc. 2016; 138: 4318
    • 9b Zhang J. Niu D. Brinker VA. Hoye TR. Org. Lett. 2016; 18: 5596
  • 10 Representative Procedure for the Formation of Spirocyclic Benzopyran 17a N-(Hepta-3,5-diyn-1-yl)-4-methyl-N-(penta-1,3-diyn-1-yl)benzenesulfonamide (15, 30 mg, 93 μmol) and 2-cycloheptylideneacetaldehyde (16a, 26 mg, 188 μmol, 2 equiv) were added to a glass vial. DCE (5 mL) was added to bring the concentration of the tetrayne to 0.02 M. The vial was sealed with a Teflon-lined cap and placed in an oil bath held at 100 °C. After 15 h at 100 °C, the cooled solution was partitioned between EtOAc and 30% aqueous n-butylamine (to remove excess enal, which had a very similar Rf on silica gel to that of 17a). The EtOAc layer was dried (Na2SO4), filtered, and concentrated. Purification of the residue by MPLC (hexanes/EtOAc = 5:1) gave the spirocyclic product 5′-methyl-4′-(prop-1-yn-1-yl)-1′-tosyl-2′,3′-dihydro-1′H-spiro{cycloheptane-1,7′-pyrano[2,3-g]indole} (17a, 30 mg, 65 mol, 70%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 7.39 (d, J = 8.3 Hz, 2 H, SO2ArHortho ), 7.17 (d, J = 8.5 Hz, 2 H, SO2ArHmeta ), 6.90 (d, J = 9.9 Hz, 1 H, H1), 5.73 (d, J = 9.9 Hz, 1 H, H2), 3.96 (t, J = 7.4 Hz, CH2NTs), 2.39 (s, 3 H, SO2ArCH3), 2.26 (s, 3 H, ArCH3), 2.16 (t, J = 7.4 Hz, 2 H, CH2 CH2NTs), 2.15–2.08 (non-first-order m, 2 H), 2.02 (s, 3 H, –C≡CCH3 ), 1.82–1.67 (m, 6 H), 1.63–1.55 (m, 2 H), and 1.53–1.45 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 150.4, 144.1, 136.0, 134.6, 131.3, 130.6, 129.8, 127.8, 126.0, 120.0, 119.9, 116.0, 93.1, 80.4, 76.6, 53.1, 39.1, 29.6, 28.7, 22.0, 21.8, 13.8, and 4.7. IR: 2921, 2856, 1598, 1354, 1164, 1089, 1017, 913 and 814 cm–1. HRMS (ESI-TOF): m/z calcd for C28H31NNaO3S+ [M + Na]+: 484.1917; found: 484.1920.