A combined DFT and NMR investigation of the zinc organometallic intermediate proposed in the syn-selective tandem chain extension-aldol reaction of β-keto esters.
The tandem chain extension-aldol (TCA) reaction of β-keto esters provides an α-substituted γ-keto ester with an average syn:anti selectivity of 10:1. It is proposed that the reaction proceeds via a carbon-zinc bound organometallic intermediate potentially bearing mechanistic similarity to the Reformatsky reaction. Evidence, derived from control Reformatsky reactions and a study of the structure of the TCA intermediate utilizing DFT methods and NMR spectroscopy, suggests the γ-keto group of the TCA intermediate plays a significant role in diastereoselectivity observed in this reaction. Such coordination effects have design implications for future zinc mediated reactions.
Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
Karelle S
KS
Aiken
Wilhelm A
WA
Eger
Craig M
CM
Williams
Carley M
CM
Spencer
Charles K
CK
Zercher
D000447:Aldehydes / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011789:Quantum Theory; D015032:Zinc / Q000737:chemistry*
D000447:Aldehydes; D004952:Esters; D007659:Ketones; D009942:Organometallic Compounds; C116609:3-hydroxybutanal; D015032:Zinc