Microwave-assisted ethylene–alkyne cross-metathesis: synthesis of chiral 2-(N-1-acetyl-1-arylmethyl)-1,3-butadienes

Chiral 1-arylpropargyl amides, which are resistant to undergoing ethylene–alkyne cross-metathesis at atmospheric pressure, were reacted under microwave irradiation to afford enantiomerically enriched 2-(N-1-acetyl-1-arylmethyl)-1,3-butadienes within a few minutes. Enantiomerically enriched amides underwent ethylene–alkyne cross-metathesis with retention of configuration at the propargylic/allylic position. A series of chiral 2-(N-1-acetyl-1-arylmethyl)-1,3-butadienes were synthesised with ee ⩾95%; these latter compounds could be used as building blocks for the synthesis of new antifungal and antiaromatase agents.

Figure optionsDownload as PowerPoint slide

(R)-2-(N-1-Acetyl-1-phenylmethyl)-1,3-butadieneC13H15NOEe 96%[α]D20 = +34.0 (c 0.8, CH3Cl)Source of chirality: (R)-N-1-acetyl-1-phenyl-propynylamineAbsolute configuration: R

(R)-2-(N-1-Acetyl-1-(4-fluorophenyl)-methyl)-1,3-butadieneC13H14FNOEe 97%[α]D20 = +36.0 (c 1.0, CH3Cl)Source of chirality: (R)-N-1-acetyl-1-(4-fluorophenyl)-propynylamineAbsolute configuration: R

(R)-2-(N-1-Acetyl-1-(4-chlorophenyl)-methyl)-1,3-butadieneC13H14ClNOEe 95%[α]D20 = +69.0 (c 1.0, CH3Cl)Source of chirality: (R)-N- 1-acetyl-1-(4-chlorophenyl)-propynylamineAbsolute configuration: R

(R)-2-(N-1-Acetyl-1-(3-fluorophenyl)-methyl)-1,3-butadieneC13H14FNOEe 96%[α]D20 = +20.0 (c 0.6, CH3Cl)Source of chirality: (R)-N-1-acetyl-1-(3-fluorophenyl)-propynylamineAbsolute configuration: R

(R)-2-(N-1-Acetyl-1-(3-methylphenyl)-methyl)-1,3-butadieneC14H17NOEe 95%[α]D20 = +35.0 (c 0.7, CH3Cl)Source of chirality: (R)-N-1-acetyl-1-(3-methylphenyl)-propynylamineAbsolute configuration: R