Abstract
The first stereocontrolled synthesis of the C(1)-C(13) fragment of cytotoxic macrolides dolabelides is reported. The C(3), C(7), C(9) and C(11) hydroxyl-bearing stereocenters were installed using ruthenium-mediated asymmetric hydrogenation reactions of the adequate β-keto esters and β-hydroxy ketone.
Key words
asymmetric catalysis - hydrogenation - ruthenium - total synthesis - natural products
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Typical Procedure for the Synthesis of Ikariya-Mashima’s Catalyst with (
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Typical Procedure for the Hydrogenation Reaction with Ikariya-Mashima’s Catalyst 10.
A solution of b-keto ester 9 (110 mg, 0.30 mmol) in degassed MeOH (2.0 mL) was added to Ikariya-Mashima’s catalyst 10 (6.0 mg, 0.004 mmol) in a round bottom tube via cannula. The reaction vessel was placed in a stainless steel autoclave, which was purged with hydrogen and pressurized to 80 bar. After stirring for 8 h at r.t., hydrogen was vented and the reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography (C6 H12 -EtOAc = 8.5:1.5) to give 11 (102 mg, 0.28 mmol, 93%, de = 98%) as a pale yellow oil.
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