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Highly Stereoselective Synthesis of ( E )- and ( Z )-α-Fluoro-α,β-unsaturated Esters and ( E )- and ( Z )-α-Fluoro-α,β-unsaturated Amides from 1-Bromo-1-fluoroalkenes via Palladium-Catalyzed Carbonylation Reactions

2005; American Chemical Society; Volume: 70; Issue: 11 Linguagem: Inglês

10.1021/jo050314a

1520-6904

Jianjun Xu, Donald J. Burton,

Oxidative Organic Chemistry Reactions

The highly stereoselective synthesis of (E)- and (Z)-α-fluoro-α,β-unsaturated esters and (E)- and (Z)-α-fluoro-α,β-unsaturated amides is described. 1-Bromo-1-fluoroalkenes (E/Z ≈ 1:1), which are readily available starting materials, have been found to isomerize to high E/Z ratios after storage at −20 °C for 1 week or by photolysis at 254 nm. Since the (E)-isomers have been found to react faster than the corresponding (Z)-isomers at room temperature in Pd(0)-catalyzed reactions, the palladium-catalyzed carboalkoxylation of high E/Z 1-bromo-1-fluoroalkenes lead to a high Z/E (Z/E ≥ 98:2) ratio of the α-fluoro-α,β-unsaturated esters. When 1-bromo-1-fluoroalkenes (E/Z ≈ 1:1) were reacted with HCOOH/NBu3/Pd(II)/DMF, the (E)-isomer was selectively reduced, and the remaining (Z)-1-bromo-1-fluoroalkenes were recovered in essentially pure isomeric form. The resulting mixture of (Z)-1-bromo-1-fluoroalkenes and the reduced products underwent similar palladium-catalyzed carboalkoxylation reactions at 70 °C, and the (E)-α-fluoro-α,β-unsaturated esters were stereospecifically obtained. This methodology was also successfully applied for the stereospecific synthesis of (Z)- and (E)-α-fluoro-α,β-unsaturated amides: the palladium-catalyzed carboamidation reaction of high E/Z and (Z)-1-bromo-1-fluoroalkenes lead to pure (Z)- and (E)-α-fluoro-α,β-unsaturated amides, respectively.