Generation and tandem reactions of 1-alkenyl-1,1-heterobimetallics: practical and versatile reagents for organic synthesis.
A practical and straightforward method for generation of versatile 1-alkenyl-1,1-heterobimetallic intermediates and their application to construction of functionalized building blocks are disclosed. Beginning with readily available air-stable 1-alkynyl-1-boronate esters, hydroboration with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ transmetallation with dialkylzinc reagents furnishes 1-alkenyl-1,1-heterobimetallic intermediates. Direct treatment with aldehydes followed by workup allows isolation of B(pin)-substituted allylic alcohols in 70-95% yield. The B(pin)-substituted allylic alcohols react with NBS to afford (E)-alpha,beta-unsaturated aldehydes in 51-77% yield via a semipinacol-type rearrangement. In situ treatment of 1-alkenyl-1,1-heterobimetallic intermediates with aldehydes followed by TBHP oxidation enables the preparation of alpha-hydroxy ketones. Under optimized conditions, addition of 1-alkenyl-1,1-heterobimetallic intermediates to a variety of protected alpha- and beta-hydroxy aldehydes proceeds with good to excellent control over diastereoselectivity to furnish differentially protected dihydroxy ketones. The 1-alkenyl-1,1-heterobimetallic intermediates have also been employed in tandem aldehyde addition/Suzuki cross-coupling reactions to provide densely functionalized allylic alcohols in good to excellent yields.
Li
Hongmei
H
P. Roy and Diana T. Vagelos Laboratories, University of Pennsylvania, Department of Chemistry, 231 South 34th Street, Philadelphia, Pennsylvania, 19104-6323, USA.
Carroll
Patrick J
PJ
Walsh
Patrick J
PJ
D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
D000438:Alcohols; D000447:Aldehydes; D000475:Alkenes; D001897:Boronic Acids; D007202:Indicators and Reagents; D007659:Ketones; D009942:Organometallic Compounds; D015032:Zinc