A Radical Approach for the Construction of the Tricyclic Core of Stemoamide

Abstract

A rapid synthesis of (±)-9,10-bis-epi-stemoamide is presented. Three of the four contiguous stereocenters of this compound were set in a diastereoselective radical 7-exo-trig cyclization, which also allowed the construction of the tricyclic core of the molecule.

Key words

radical cyclization - metathesis - stereoselective syn­thesis

References

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10

For general conditions of cyclization see ref. [11]

11

9,10-bis- epi -Stemoamide ( 10):
To a stirred solution of 9 (48 mg, 0.15 mmol) and AIBN (5 mg, 0.03 mmol) in degassed benzene (30 mL) at reflux, a solution of Bu₃SnH (100 µL, 0.37 mmol) in benzene (3 mL) was added over 4 h via a syringe pump. The crude mixture was treated with a sat. aq solution of KF, extracted by CH₂Cl₂, dried over MgSO₄, filtered, concentrated under reduced pressure, and purified by chromatography on silica gel (gradient: CH₂Cl₂ then CH₂Cl₂-MeOH 95:5) to afford compound 10 (6.7 mg, 0.03 mmol, 20%) as a single diastereomer. ¹H NMR (300 MHz, CDCl₃): δ = 1.39 (d, J = 7.2 Hz, 3 H), 1.61-2.15 (br m, 5 H), 2.23-2.62 (m, 5 H), 2.78 (ddd, J = 13.9, 10.4, 3.4 Hz, 1 H), 3.63 (dd, J = 9.0, 7.2 Hz, 1 H), 4.18 (dt, J = 13.9, 4.5 Hz, 1 H), 4.62 (ddd, J = 10.6, 7.9, 3.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 15.9, 24.0, 25.5, 28.9, 30.1, 39.1, 44.1, 50.9, 60.5, 80.7, 174.6, 177.9. MS (EI, 70eV): m/z (%) = 224 (12) [MH⁺ ], 223 (87) [M⁺ ], 208 (41), 180 (44), 98 (100), 97 (59).