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Synlett 2005(16): 2501-2503  
DOI: 10.1055/s-2005-872696
LETTER
© Georg Thieme Verlag Stuttgart · New York

First Intramolecular [6+4] Cycloaddition of Tropone and a Furan Moiety: Rapid Entry into a Highly Functionalized Ingenane Skeleton

James H. Rigby*, Gaëlle Chouraqui
Department of Chemistry, Wayne State University, Detroit, MI 48202-3489, USA
Fax: +1(313)5773585; e-Mail: jhr@chem.wayne.edu;
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Publication History

Received 21 July 2005
Publication Date:
21 September 2005 (online)

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Abstract

The expeditious construction of a highly functionalized ABC core of ingenol via an intramolecular, metal-free [6+4] ­cycloaddition of cycloheptatrienone and furan is reported.

Key words

ingenol - cycloaddition - bicyclic compound - hetero­cycle - furan

21

The cyclized product was fully characterized by 1H NMR, 13C NMR, NOE, COSY spectroscopic analyses and the structure was also confirmed by IR and HRMS. A solution of 2.2 g of 3a (3.28 mmol, 1.0 equiv) in 15 mL of benzene was refluxed during 3 h. The solution was concentrated in vacuo. The crude oil was purified by flash chromatography on silica gel (PE-Et2O, 97:03) and gave 2a (1.32 g, 60%) as a red oil and as a mixture of two diastereomers (60:40). IR (neat): 2928, 2856, 1710, 1609, 1103, 1034, 836, 700 cm-1. 1H NMR (500 MHz, CDCl3): diastereomer 1: δ = 7.60-7.56 (m, 4 H, Ph), 7.40-7.31 (m, 6 H, Ph), 6.48 (s, 1 H, CH vinylic cycle B), 5.87 (d, J = 11.5 Hz, 1 H, Hc), 5.68-5.60 (m, 2 H, diene), 5.36-5.05 (m, 3 H, Hb, H junction cycle B and C, CH diene), 4.74 (s, 1 H, CH-OMOM), 4.67-4.62 (m, 2 H, CH2-OTBS), 3.82 (s, 2 H, CH2 of MOM), 3.38 (s, 3 H, Me of MOM), 1.38 (s, 3 H, Ha), 1.12 (s, 9 H, t-Bu), 0.72 (s, 9 H, t-Bu), -0.24 (s, 6 H, Me of TBS) ppm; diastereomer 2: δ = 7.60-7.56 (m, 4 H, Ph), 7.40-7.31 (m, 6 H, Ph), 6.47 (s, 1 H, CH vinylic cycle B), 5.81 (d, J = 12.0 Hz, 1 H, Hc), 5.68-5.60 (m, 2 H, diene), 5.36-5.05 (m, 3 H, Hb, H junction cycle B and C, CH diene), 4.80 (s, 1 H, CH-OMOM), 4.67-4.62 (m, 2 H, CH2-OTBS), 3.82 (s, 2 H, CH2 of MOM), 3.12 (s, 3 H, CH3 of MOM), 1.52 (s, 3 H, Ha), 1.12 (s, 9 H, t-Bu), 0.72 (s, 9 H, t-Bu), -0.24 (s, 6 H, Me of TBS) ppm. 13C NMR (125 MHz, CDCl3): diastereomer 1: δ = 1° C: 55.8, 27.8 (3 C), 25.8 (3 C), 24.2, -5.5 (2 C); 2° C: 95.2, 57.5; 3° C: 136.1 (4 C), 131.2, 129.5 (2 C), 127.8 (4 C), 124.5, 121.0, 119.9, 110.8, 99.9, 99.3, 76.3; 4° C: 186.7, 168.9, 155.5, 149.3, 140.7, 139.7, 133.5 (2 C), 18.9, 18.2 ppm; diastereomer 2: δ = 1° C: 55.6, 27.7 (3 C), 25.8 (3 C), 22.3, -5.5 (2 C); 2° C: 94.5, 57.5; 3° C: 136.1 (4 C), 131.1, 129.5 (2 C), 127.8 (4 C), 124.3, 121.0, 119.0, 110.6, 99.9, 99.3, 76.2; 4° C: 186.7, 168.6, 155.5, 149.3, 140.5, 139.4, 133.4 (2 C), 18.9, 18.2 ppm. HRMS: m/z = 668.3350.