Total Synthesis of (±)-3-Hydroxy-β-ionone through a Ring-Closing Enyne Metathesis

Abstract

The total synthesis of (±)-3-hydroxy-β-ionone, a bisnor­sesquiterpene having allelopathic activity, has been accomplished employing an enyne metathesis for the construction of the C1-C8 segment and two-carbon elongation via a nitrile oxide-alkene [3+2] cycloaddition as the key steps.

Key words

enyne metathesis - total synthesis - ionones - nitrile oxide - cycloaddition

References and Notes

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11

Analytical Data
IR (neat): 3334, 2922, 1460, 1362, 1049, 918 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 6.16 (ddd, J = 13.2, 7.2, 1.6 Hz, 1 H), 5.26 (dd, J = 7.2, 2.4 Hz, 1 H), 4.98 (dd, J = 13.2, 2.4 Hz, 1 H), 4.05-3.92 (m, 1 H), 2.35 (dd, J = 16.8, 5.6 Hz, 1 H), 2.01 (dd, J = 16.8, 6.8 Hz, 1 H), 1.75 (ddd, J = 12.0, 3.2, 2.0 Hz, 1 H), 1.71 (s, 3 H), 1.45 (t, J = 12.0 Hz, 1 H), 1.35 (br s, 1 H), 1.05 (s, 3 H), 1.04 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 138.1 (Cq), 134.7 (CH), 125.6 (Cq), 118.7 (CH₂), 65.1 (CH), 48.3 (CH₂), 42.2 (CH₂), 36.6 (Cq), 30.0 (CH₃), 28.3 (CH₃), 21.2 (CH₃). ESI-HRMS: m/z calcd for C₁₁H₁₈ONa [M + Na]⁺: 189.1255; found: 189.1255.

12

Analytical Data
IR (neat): 3345, 2965, 2925, 1041, 892 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 5.99 (s, 1 H), 4.98 (s, 1 H), 4.79 (s, 1 H), 3.99-3.92 (m, 1 H), 2.37 (dd, J = 16.4, 3.2 Hz, 1 H), 2.30 (dd, J = 16.4, 9.6 Hz, 1 H), 1.84 (ddd, J = 13.2, 3.6, 1.6 Hz, 1 H), 1.81 (s, 3 H), 1.70 (dd, J = 13.2, 9.6 Hz, 1 H), 1.45 (br s, 1 H), 1.15 (s, 3 H), 1.14 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 153.5 (Cq), 133.1 (Cq), 127.9 (CH), 111.7 (CH₂), 67.7 (CH), 52.0 (CH₂), 43.9 (CH₂), 37.2 (Cq), 31.8 (CH₃), 29.4 (CH₃), 26.7 (CH₃). ESI-HRMS: m/z calcd for C₁₁H₁₈ONa [M + Na]⁺: 189.1255; found: 189.1258.

13

The Wittig and Horner-Wadsworth-Emmons reactions of 13a,b were examined under various conditions; however, only starting aldehyde was recovered.

14

It has been reported that the aldol reaction of 13a with acetone provided 1; however, the yield was not described. [7e] When the reaction was attempted under the same conditions as reported, 1 was not produced at all.

18

Analytical Data
IR (neat): 3409, 2960, 2926, 1672, 1606, 1363, 1257, 1051 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.21 (d, J = 16.4 Hz, 1 H), 6.11 (d, J = 16.4 Hz, 1 H), 4.06-3.95 (m, 1 H), 2.44 (dd, J = 17.6, 5.2 Hz, 1 H), 2.30 (s, 3 H), 2.09 (dd, J = 17.6, 9.6, 1 H), 1.80 (ddd, J = 12.4, 3.2, 2.0 Hz, 1 H), 1.78 (s, 3 H), 1.49 (t, J = 12.4 Hz, 1 H), 1.25 (br s, 1 H), 1.12 (s, 3 H), 1.11 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 198.5 (Cq), 142.3 (CH), 135.7 (Cq), 132.4 (CH), 132.2 (Cq), 64.5 (CH), 48.4 (CH₂), 42.8 (CH₂), 36.9 (Cq), 30.1 (CH₃), 28.6 (CH₃), 27.3 (CH₃), 21.5 (CH₃). ESI-HRMS: m/z calcd for C₁₃H₂₁O₂
[M + H]⁺: 209.1542; found: 209.1539.

19

The optical resolution has been successfully achieved by Khachik et al. [7h]