Efficient Enantioselective Total Synthesis of (+)-Helianane

Abstract

The enantiocontrolled total synthesis of (+)-helianane, a marine-derived heterocyclic sesquiterpene, has been accomplished with an efficient chirality transfer during the Me₃Al-mediated aromatic Claisen rearrangement and a ring-closing metathesis as the key steps. The absolute structure of the natural product has been firmly established by total synthesis.

Key words

metathesis - total synthesis - terpenoids - Claisen rearrangement - helianane

References and Notes

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13

The regioisomer generated from the S_N2′ process was obtained in 14% yield. The stereochemistry and the ee of it have not been determined.

20

Analytical Data for Helianane (1)
[α]_D +24.0 (c 2.28, CH₂Cl₂) {Lit.^¹ [α]_D +8.0 (c 1.01, CH₂Cl₂)}. IR (neat): 2973, 2926, 1456, 1382, 1256, 1138 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.06 (d, J = 8.0 Hz, 1 H), 6.88 (d, J = 8.0 Hz, 1 H), 6.71 (d, J = 1.5 Hz, 1 H), 3.19 (br s, 1 H), 2.27 (s, 3 H), 1.78-1.70 (m, 1 H), 1.62-1.56 (m, 1 H), 1.52 (m, 2 H), 1.46-1.32 (m, 2 H), 1.41 (s, 3 H), 1.28 (s, 3 H), 1.25 (d, J = 7.0 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 153.0, 138.8, 135.3, 125.8, 125.8, 124.9, 80.9, 39.7, 38.1, 31.5, 29.2, 26.7, 21.9, 21.2, 20.9. ESI-HRMS:
m/z calcd for C₁₅H₂₂ONa [M⁺ + Na]⁺: 241.1568; found: 241.1577.