A Cyclopentane, Cyclopentene and Cyclopentanone Annulation Methodology

Dilithiated vicinal diester route to sesquiterpenes. The total synthesis of (.+-.)-vetiselinene and the formal synthesis of other eudesmane sesquiterpenes

“…Reduction of 11 with lithium in a mixture of liquid NH3 and dimethoxyethane at low temperature gave the alcohol 12, which was not purified but was oxidized directly to the ketone 13 with pyridinium chlorochromate in 61% overall yield from 11. The spectral properties of compounds [11][12][13] were in accord with those reported by Torii and co-workers.17 The ketone 13 was then treated with isopropylmagnesium chloride in THF at -50 °C, and the resulting alcohol 14 was not purified but was dehydrated with H2S04 to give a mixture of ketones in 42% yield. This mixture was separated by HPLC to give 15, 16, 17, and 18 in the approximate proportions 6:2:1:1.…”

“…15: 38.8 mg (18%); MS, m/e 206.1681 (C14H220 requires 206.1670) , 206 (M+), 191,163 (100%); NMR, see discussion; 13C NMR 150.5,141.5, 116.9, 106.1, 44.9, 42.4, 41.9, 37.2, 35.0, 34.6, 25.4, 23.7, 21.5, 21.1, 16.9; IR 1705 cm"1. 16: 12.5 mg (6%); MS, m/e 206.1675 (C14H220 requires 206.1670) , 206 (M+), 191,163 (100%); NMR 5.34 (br s, 1 H), 2.60-1.38 (m, 13 ), 1.05 (s, 3 ), 0.95 (d, 6 H, J = 6.8 Hz); IR 1718 cm"1. 17: 8.4 mg (4%); MS, m/e 206 (M+), 191, 163, 131 (100%); NMR 5.05 (br s, 1 ), 2.42-1.46 (m, 13 ), 1.05 (s, 3 ), 0.94 (d, 6 H, J = 6.8 Hz); IR 1705 cm'1.…”

“…(100) C5H8OI, 201,1633 (12), 111.0478 (19) C6H702,107.0828 (16), 93.0700 (17), 81.0693 (21), 79.0538 (20).…”

Iso‐maleimycin, a Constitutional Isomer of Maleimycin, from Streptomyces sp. QL37

“…A key step was the preparation of compound 14b by the introduction of the double bond. According to literature, 17 was treated with an excess of LDA to form the mono‐enolate, which was treated with a stoichiometric amount of iodine in THF at –78 °C to generate the corresponding iodinated intermediate. This intermediate then likely reacted with a second equivalent of LDA providing the corresponding elimination product 14b , which was isolated in 74 % yield.…”

“…Dimethyl 4‐[( tert ‐Butyldiphenylsilyl)oxy]cyclopent‐1‐ene‐1,2‐dicarboxylate (14b): According to a modified literature procedure, LDA was generated by adding n BuLi (1.6 m solution in hexanes, 7.6 mL, 12.1 mmol) to a solution of N,N ‐diisopropylamine * (1.8 mL, 12.8 mmol) in dry THF (10 mL), at –78 °C. Compound 17 (2.35 g, 5.34 mmol) was dissolved in dry THF (25 mL) and added to the reaction mixture dropwise.…”