Synthetic Studies toward the Total Synthesis of Chlorahololide A

Abstract

The highly stereoselective synthesis of core framework 4, a pivotal intermediate for the total synthesis of chlorahololide A, is reported. The approach features t-BuCu-mediated stereoselective reduction of α,β-unsaturated diketone 8, Wharton transposition, Simmons-Smith cyclopropanation and cascade enol lactonization.

Key words

chlorahololide A - Hajos-Parrish ketone - Wharton transposition - cyclopropanation - enol lactonization

References and Notes

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14

The same operative procedure should be conducted to ensure that the starting material is completely consumed. For details, see the Supporting Information.

15

See the Supporting Information for details. CCDC 804060 (4) and 804061 (14) contain the supplementary crystallogra-phic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

20

Data of the Core Fragment 4
[α]_D ^²8 56.2 (c 0.12, CHCl₃); mp 133-135 ˚C. IR (film): 2921, 2850, 1735, 1464, 1374, 1265, 1045 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 6.16 (s, 1 H), 4.39 (t, J = 5.2 Hz, 1 H), 2.60-2.40 (m, 2 H), 2.20-2.10 (m, 1 H), 1.89 (s, 3 H), 1.80-1.65 (m, 1 H), 1.65-1.50 (m, 1 H), 1.30-1.20 (m, 1 H), 1.09 (s, 3 H), 0.91 (s, 9 H), 1.80-1.65 (m, 1 H), 0.10 (s, 3 H), 0.07 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 171.2, 149.4, 149.3, 122.1, 121.0, 72.9, 61.9, 42.1, 29.1, 26.2, 25.8, 23.3, 21.4, 18.2, 12.1, 8.5, -4.7, -5.3. ESI-MS: m/z = 369.2 [M + Na]⁺. ESI-HRMS: m/z calcd for C₂₀H₃₀O₃SiNa⁺ [M + Na]⁺: 369.1862; found: 369.1856.