Formal Synthesis of Teadenols via Palladium-Catalyzed 6-endo Cyclization of an Epoxyphenol

To the memory of late Prof. Toshiyuki Kan.

Abstract

Formal syntheses of teadenols A and B are achieved via a key Pd-catalyzed 6-endo cyclization of a phenol possessing a vinyl ­epoxide moiety. Although 5-exo and 6-endo cyclizations compete during cyclizations of epoxides with a nucleophilic moiety at the 5-position, 6-endo cyclization is realized by using a palladium catalyst.

Key words

6-endo cyclization - formal synthesis - palladium - teadenol - vinyl epoxide

Publication History

Received: 31 May 2022

Accepted after revision: 03 July 2022

Accepted Manuscript online:
03 July 2022

Article published online:
29 July 2022

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• 13 Physical Data of Compound 4 IR (ATR): 1716, 1618, 1592, 1500 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.41–7.26 (m, 10 H), 6.25 (d, J = 2.3 Hz, 1 H), 6.14 (d, J = 2.2 Hz, 1 H), 5.99 (d, J = 1.6 Hz, 1 H), 5.00 (s, 2 H), 4.98 (s, 2 H), 4.80 (q, J = 2.7 Hz, 1 H), 4.34 (d, J = 2.2 Hz, 1 H), 3.17 (dd, J = 18.0, 2.8 Hz, 1 H), 2.97 (dd, J = 18.0, 5.6 Hz, 1 H), 2.17 (d, J = 1.5 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 168.7, 158.8, 157.9, 154.8, 154.2, 136.8, 136.8, 128.6, 128.6, 128.0, 128.0, 127.5, 127.3, 119.4, 99.8, 94.5, 94.3, 71.2, 70.2, 70.1, 69.3, 24.0, 20.7. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₇H₂₄NaO₅: 451.1521; found: 451.1515.
• 14 Physical Data of Compound 7 IR (ATR): 1728, 1589, 1498, 1437, 1376 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.43–7.32 (m, 10 H), 6.30 (d, J = 2.3 Hz, 1 H), 6.21 (d, J = 2.3 Hz, 1 H), 5.88 (t, J = 1.8 Hz, 1 H), 5.05 (d, J = 11.9 Hz, 1 H), 5.02 (d, J = 11.9 Hz, 1 H), 5.01 (s, 2 H), 4.50 (td, J = 10.8, 5.7 Hz, 1 H), 4.23 (d, J = 10.8 Hz, 1 H), 3.29 (dd, J = 16.0, 6.1 Hz, 1 H), 2.83 (dd, J = 16.0, 6.1 Hz, 1 H), 2.17 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 162.9, 159.1, 157.8, 157.4, 154.4, 136.63, 136.61, 128.64, 128.60, 128.1, 128.0, 127.5, 127.0, 116.9, 101.7, 94.61, 96.57, 74.1, 72.8, 70.2, 70.0, 26.5, 17.6. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₇H₂₄NaO₅: 451.1521; found: 451.1524.