Theoretical studies in organolithium chemistry

Kinetics and Mechanism of Ketone Enolization Mediated by Magnesium Bis(hexamethyldisilazide)

“…The intramolecular proton transfer reaction in the rate-determining step is reminiscent of the classic Ireland model of lithium amide-mediated enolization reactions . While Ireland proposed a chair-like structure for the transition state, computational studies support a much less puckered structure. 6f,13a The observation of a very large primary isotope effect strongly supports such a modified Ireland mechanism. Achieving such a large isotope effect is generally accepted to require a nearly linear C−H−N trajectory, as well as a central transition state (since early or late transition states lead to reduced isotope effects).…”

“…The Mg{N(SiMe 3 ) 2 } 2 fragment is intrinsically chiral in the reactive three-coordinate complex since the planes of the amides are canted around the coordination plane like two blades of a three-bladed propeller. Furthermore, the tilt of the amide orients the nitrogen lone pair correctly for proton transfer, as judged from the calculated structures for intramolecular lithium-mediated enolizations. 6f,13a The helical sense of chirality of the Mg(amide) 2 fragment determines which enantiotopic axial proton can be deprotonated; the mismatched proton cannot align with the lone pair on nitrogen (Scheme ). Thus, any bias provided by the chiral amides that favors one helical conformation over the other could play a determining role in the observed selectivity.…”

“…Crystallographic data for 1 , 3 , and 4 in CIF format; the complete list of authors for refs c and ; tables summarizing (i) bond lengths and angles for 1 , (ii) the kinetic data, and (iii) the diffusion NMR experiments; Eyring plot of the reaction of Mg(HMDS) 2 with propiophenone; plot of absorbance versus time for the disappearance of intermediate 2 ; 1 H NMR spectra of free propiophenone and intermediate 2 in dichloromethane- d 2 ; and details of the calculations. This material is available free of charge via the Internet at .…”

“…Lithium amides, such as lithium diisopropylamide (LDA), lithium 2,2,6,6-tetramethylpiperidide (LTMP), and lithium hexamethyldisilazide (LiHMDS), have evolved to become the dominant bases of choice to mediate kinetic enolization reactions. , These reagents are highly selective in the deprotonation of ketonic substrates as they combine the properties of relatively large steric encumbrance, strong Brønsted basicity, and low nucleophilicity. Numerous theoretical, solid-state, , solution, and kinetic investigations 10 of lithium-mediated enolizations have revealed an astonishing degree of complexity underlying these seemingly simple transformations. In this regard, the systematic spectroscopic and mechanistic studies of lithium amide-mediated enolization reactions by Collum are particularly revealing. − The picture that has emerged from this work is that no single mechanism is adequate to describe these proton transfer processes.…”

Overview of Carbanion Dynamics and Electrophilic Substitutions in Chiral Organolithium Compounds

“…11 A recent review discusses the nature of the C–Li bond, and concludes that “the nature of the C–Li bond varies from compound to compound”, [but] “the covalent components cannot be neglected”. 12 …”