Mechanistic studies on the Heck-Mizoroki cross-coupling reaction of a hindered vinylboronate ester as a key approach to developing a highly stereoselective synthesis of a C1-C7 Z,Z,E-triene synthon for viridenomycin.
Mechanistic studies of the Heck-Mizoroki reaction of a vinylboronate ester with electronically different (four-substituted) aryl iodides shows that electron donors accelerate the cross-coupling, demonstrating that the oxidative addition step is not rate determining and that there is development of some degree of positive charge in the rate determining step. These results were used as a basis to allow the development of reaction conditions for the Heck-Mizoroki coupling of a hindered vinylboronate ester with electron deficient methyl cis-2-iodoacrylate. The resulting dienylboronate ester was converted through a series of highly stereoselective iodo-deboronations and Heck-Mizoroki reactions into a trienyl iodide precursor for further application in the total synthesis of viridenomycin.
Batsanov
Andrei S
AS
University of Durham, Department of Chemistry, Sciences Laboratories South Road DH1 3LE, Durham, United Kingdom.
Knowles
Jonathan P
JP
Whiting
Andrew
A
D001888:Boric Acids / Q000737:chemistry; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D001888:Boric Acids; D004952:Esters; D007769:Lactams; D014753:Vinyl Compounds; C519434:vinylboronate ester; C010374:viridinomycin; C032688:boric acid