Alkali Metal Counterion Control of Enolate Protonation Stereoselectivity

Abstract

[reaction: see text] Generation of the lithium salt of the norbornenol shown (M = H) followed by quenching with aqueous NH(4)Cl solution gives predominantly the beta-epimeric ketone 6. Similar production of the potassium alkoxide leads instead to the alpha-epimer (99:1). These results reveal the potential importance of alkali metal counterions as stereocontrol elements.

Carbanions and Electrophilic Aliphatic Substitution

“…11 Alkali metal counterion has been found to control the enolate protonation stereoselectivity. 12 This remarkable phenomenon has been reported for lithium and potassium enolates of a norborneol derivative.…”

“…71 Dimeric lithium acetylide has reacted via a monosolvated monomer-based transition structure. The robust tetrahedral intermediate (12) forms sequentially a C(1) 2:2 mixed tetramer with the excess lithium acetylide and a 1:3 (alkoxide-rich) mixed tetramer. The stabilities of the mixed tetramers are consistent with a pronounced autoinhibition.…”

Synthesis of Limonoid Natural Products

“…[64] The intricate polycyclic nature of these tetranortriterpenoids has largely discouraged targeted synthetic investigations. Interestingly, the stereoselectivity of protonation [68] of this intermediate is highly dependent on the nature of the alkali metal counterion. [65] An improved strategy targeting a complex ABC ring scaffold was reported in 2007 [66] by the same group (Scheme 14).…”

“…Hong and Paquette reported the first studies aimed at dumsin in which (-)-bornyl acetate was elaborated to a BCD ring fragment by a synthetic approach involving an intramolecular anionic oxy-Cope rearrangement as a key step. This unique stereocontrol element has been rationalized [68] by the notion that the reactive potassium salt (Int-I) gives rise to the thermodynamically favored product whereas the relatively stable lithium enolate can be subject to kinetically controlled protonation upon quenching at low temperature. Again, an enantiodefined oxy-Cope rearrangement of an exo-norbornenol (136) was projected to set four stereogenic centers of a hypothesized cis-hydrindanone intermediate with absolute configuration relatable to dumsin.…”

Reactions of Aldehydes and Ketones and their Derivatives

“…292 A stereoselective enolate protonation has been achieved by changing the counterion of the chiral alkoxide base employed: the lithium alkoxide-generated enolate gives ee close to 90% of the β-epimeric ketone product, whereas the use of the potassium cation gives 99% α-epimer. 293 A chiral BINAP-diphosphine complexed to silver(I), with fluoride as counterion, catalyses the enantioselective protonation of TMS-enolates, giving ketones with a ee tertiary asymmetric α-carbon in up to 99% ee. 294 …”