Experimental and Computational Evidence of the Biradical Structure and Reactivity of Titanium(IV) Enolates

Abstract

Quantum chemical calculations have unveiled the unexpected biradical character of titanium(IV) enolates from N-acyl oxazolidinones and thiazolidinethiones. The electronic structure of these species therefore involves a valence tautomerism consisting of an equilibrium between a closed shell (formally Ti(IV) enolates) and an open shell, biradical, singlet (formally Ti(III) enolates) electronic states, whose origin is to be basically found in changes of the Ti-O distance. Spectroscopic studies of the intermediate species lend support to such a model, which also turns out to be crucial for a better understanding of the overall reactivity of titanium(IV) enolates. In this context, a thorough computational analysis of the radical addition of titanium(IV) enolates from N-acyl oxazolidinones to TEMPO has permitted us to suggest an entire mechanism, which accounts for the experimental details and the diastereoselectivity of the process. All together, this evidence highlights the relevance of biradical intermediates from titanium(IV) enolates and may be a useful contribution to the foundations of a more insightful comprehension of the structure and reactivity of titanium(IV) enolates.

General and stereoselective aminoxylation of biradical titanium(iv) enolates with TEMPO: a detailed study on the effect of the chiral auxiliary

“…Taking advantage of our own studies on the aminoxylation of titanium(IV) enolates from N-acyl oxazolidinones with TEMPO, 12,13 we initially investigated the influence of chiral auxiliaries 1-6 with various combinations of oxygen and sulphur heteroatoms exo and endo to the heterocycle and bulky groups at C4 ( Figure 2). [22][23][24] By choosing such a wide range of chiral substrates we envisaged to fully understand the effect both the heteroatoms and the groups at C4 and therefore to find the most effective scaffold for this type of reaction.…”

Stereoselective Decarboxylative Alkylation of Titanium(IV) Enolates with Diacyl Peroxides

“…25 Having demonstrated the wide scope and the robustness of the alkylation, we focused our attention on its mechanism. Our working hypothesis revolved around the diradical character of the titanium(IV) enolates 16,17 of 1. The isolation of small quantities of dichloromethyl derivative II (Figure 1) supported such a hypothesis, but further proof was required.…”

“…25 In parallel, we carried out a computational analysis to gain insight into the mechanistic details of the process. 26 Keeping in mind the diradical character of the titanium(IV) enolates, 16,17 we thoroughly examined the addition of the titanium(IV) enolate from 1 to the model dilauroyl peroxide (Scheme 7). IV to form the C−C bond.…”

Stereoselective Alkylation of Chiral Titanium(IV) Enolates with tert-Butyl Peresters

“…Indeed, the tremendous success of the SOMO activation mode concept coined by MacMillan in the context of the direct and asymmetric alkylation of aldehydes illustrates the synthetic potential of the radical approach. 10 Inspired by these ideas and considering the biradical character of the titanium(IV) enolates, 11 we envisaged that they might undergo highly stereoselective alkylations provided that the required radical intermediates were generated in the reaction mixture. The feasibility of such an approach was clearly demonstrated in the alkylation of chiral N -acyl oxazolidinones with diacyl peroxides ( Scheme 1 ).…”

“…At this point, we carried out a comprehensive theoretical study to unveil the origin of the observed reactivity and selectivity. As for the reaction with diacyl peroxides, 12 DFT calculations 20 of the alkylation of 1 with perester a indicated that it also may proceed through an electron transfer from I ( Scheme 4 ), the biradical form of titanium enolates, 11 to the σ* of the O–O bond of a . Thus, a single-electron transfer (SET) redox reaction causes the formation of the Ti(IV) radical II by a one electron loss and triggers the cleavage of the O–O bond, which produces an oxygen radical and an oxygen anion species.…”