Stereoselective Synthesis of New Enantiopure Building Blocks for the Preparation of Steroids

Abstract

The enantiopure α,β-unsaturated ketone 4 was synthesised from indanone 2 by a palladium-catalysed hydrogenolysis of allylic formate 10 followed by deprotection of TBS-ether 11 and oxidation with MnO₂.

epoxidation - indane - oxidation - palladium - steroids

References

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11

Experimental Details for the Tsuji-Trost-Reaction: To a degassed solution of 10 (1.70 g, 4.31 mmol)in dioxane (15 mL) were added Pd(OAc)₂ (10 mg, 0.045 mmol) and P(n-Bu)₃ (0.040 mL, 0.18 mmol). The reaction mixture was stirred for 45 min at 90 °C. Then the reaction mixture was allowed to attain r.t. and diluted with Et₂O and H₂O. The organic layer was washed with brine, dried over Na₂SO₄, and concentrated in vacuo. Purification by silica gel column chromatography(pentane) afforded 1.06 g (70%) of 11 and 12 (4:1 mixture) as colourless oil, which was used for the next step without separation. Separation of 12 is possible using pentane/ethyl acetate (100:1), but easier at a later stage.

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13

Compound 3: R_f = 0.11 (pentane/ethyl acetate 10:1), [α]_D ²⁰ = +56.0 (c 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.76 (s, 3 H), 1.14 (s, 9 H), 1.14-1.69 (m, 5 H), 1.86-2.05 (m, 1 H), 2.10-2.20 (m, 1 H), 2.32 (dd, J = 11.9, 7.0 Hz, 1 H), 3.54 (dd, J = 9.0, 6.8 Hz, 1 H), 4.41 (m_c, 1 H), 5.60 (dt, J = 9.7, 2.6 Hz, 1 H), 5.73 (dt, J = 9.7, 1.5 Hz, 1 H). ¹³C NMR (50.3 MHz, CDCl₃): δ = 10.93, 23.72, 27.98, 30.32, 43.08, 44.08, 44.76, 67.29, 71.65, 78.27, 128.80, 129.60.
Compound 4: R_f = 0.21 (pentane/ethyl acetate 10:1), [α]_D ²⁰ = +24.3 (c 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.83 (d, J = 1.0 Hz, 3 H), 1.14 (s, 9 H), 1.53-1.69 (m, 2 H), 1.78-1.90 (m, 1 H), 2.01-2.14 (m, 1 H), 2.14 (dd, J = 16.2, 0.9 Hz, 1 H), 2.50-2.61 (m, 1 H), 2.60 (d, J = 16.2 Hz, 1 H), 3.71 (dd, J = 8.9, 7.0 Hz, 1 H), 5.96 (ddd, J = 9.9, 3.1, 0.8 Hz, 1 H), 6.81 (dd, J = 9.9, 2.3 Hz, 1 H). ¹³C NMR (50.3 MHz, CDCl₃): δ = 11.95, 23.88, 28.54, 31.30, 44.32, 46.76, 52.08, 72.63, 78.70, 129.60, 149.80, 200.60.