Versatile Zirconium Reductants and Carbon–Carbon Coupling Agents Selectively Accessible from the 2:1 Molar Aggregate of n‐Butyllithium and Zirconium(IV) Salts

Abstract

In previous studies of transition metal alkyls the 2:1 molar aggregate of n‐butyllithium and zirconium(IV) salts has been found to react both with benzylic hydrocarbons and aromatic carbonyl derivatives in diverse and useful ways. In the present study the reactions of the aggregates, 2nBuLi·ZrE4 (E = Cl, OEt), with benzaldehyde have involved carbometallation, hydrometallation and reductive dimerization (paths 1–3) in THF and were selectively achievable by temperature control alone. First, at –78 °C benzaldehyde underwent carbolithiation to give upon hydrolysis 1‐phenyl‐1‐pentanol. However, short‐term reaction times and prompt D2O quenching revealed that with Zr(OEt)4 both benzaldehyde and 1‐phenyl‐1‐pentanol were deuteriated, consistent with the presence of a phenyl(lithioxy)carbene intermediate. The observed dimerization of benzaldehyde to benzyl benzoate by lithium 2,2,6,6‐tetramethylpiperidide is also consistent with such a phenyl(lithioxy)carbene intermediate. Second, at 25 °C the 2nBuLi·ZrE4 aggregate reduced benzaldehyde exclusively to benzyl alcohol, which observation is consistent with the formation of the hydrozirconating agent, H2ZrE2. Third, heating the aggregate at reflux and subsequent reaction with benzaldehyde produced solely the reduced dimer, 1,2‐diphenyl‐1,2‐ethanediol with high stereoselectivity: E = Cl, rac/meso of 93:7 and E = OEt, rac/meso of 100:0. The proposed mechanism involves the formation of ZrE2, the epizirconation of benzaldehyde and the insertion of the second benzaldehyde into the zirconaoxacyclopropane under steric control. Finally, the high selectivity in hydrozirconation and reductive dimerization shown by 2nBuLi·ZrE4 appears at this time to be superior to that attainable with analogous titanium or hafnium aggregates.

Robust eco-friendly protocol for the preparation of γ-hydroxy-α,β-acetylenic esters by sequential one-pot elimination–addition of 2-bromoacrylates to aldehydes promoted by LTMP in 2-MeTHF

“…In fact, as previously reported, among the several advantages that 2-MeTHF shows compared to THF, there is the possibility to perform organometallic reactions at higher temperatures in the former, without observing decomposition of the solvent, as a consequence of its improved stability towards organolithiums. 34 It is worth mentioning the straight relationship existing among base employed, solvent and temperature: in fact, as reported very recently by Eisch and co-workers 47 the treatment of benzaldehyde with LTMP in hexane at 0 °C affords benzyl benzoate as a consequence of carbene formation (generated by the C-H lithiation of the formyl group), followed by the addition of this carbene to a second molecule of benzaldehyde. In contrast, by using our conditions (2-MeTHF at −40 °C) no lithiation of benzaldehyde was observed whatsoever, and thus the procedure shows an excellent chemoselective profile by directing the action of LTMP exclusively on the 2-bromoacrylic ester.…”