Titanium Enolate Chemistry at the Beginning of the 21st Century

Abstract

The aim of the microreview is to summarize the current state of knowledge in the field of titanium enolate chemistry. The authors focus on stereoselective organic syntheses promoted by titanium enolates and analyze developments in the synthetic methodology observed in this area during the last fifteen years.

Titanium(iv) enolates of cyclic ketones – stereoselective addition of cyclododecanone to aromatic aldehydes

“…syn-2-[Hydroxy(phenyl)methyl]cyclododecanone 3a R t 4.26 min; R f 0.50; colorless solid; Mp: 73 1C; FT-IR (ATR) n = 3398.3 (OH), 2929.9, 2852.0, 1701.2 (CQO), 1469.6, 1457.2, 1445.1, 1056.9, 1019.1, 999.9, 763.5, 703.7. 1 H NMR (300 MHz, CDCl 3 ): d = 7.34-7.30 (m, 4H, CH Ar ); 7.29-7.23 (m, 4H, CH Ar ); 4.92 (dd, J = 6.1, 1.5 Hz, 1H, CH(OH)); 3.05 (ddd, J = 3.8, 6.1, 9.2 Hz, 1H, aCH), 2.61 (br s, 1H, OH), 2.58 (ddd, J = 3.4, 9.9, 17.0 Hz, 1H, aCH a H b ), 2.10 (ddd, J = 3.4, 7.7, 17.0 Hz, 1H, aCH a H b ), 1.93-1.63 (m, 3H, CH ali ), 1.55-1.43 (m, 3H, CH ali ), 1.35-1.18 (m, 13H, CH ali ). 13 C NMR (75 MHz, CDCl 3 ): d = 214.9 (CQO), 142.2, 128.4, 127.7, 126.3, 73.9 (CH(OH)), 57.9 (aCH), 40.5 (aCH 2 ), 26.4, 25.7, 25.5, 24.5, 24.3, 23.…”

“…13 C NMR (75 MHz, CDCl 3 ): d = 214.9 (CQO), 142.2, 128.4, 127.7, 126.3, 73.9 (CH(OH)), 57.9 (aCH), 40.5 (aCH 2 ), 26.4, 25.7, 25.5, 24.5, 24.3, 23. 1 H NMR (300 MHz, CDCl 3 ): d = 7.47 (dd, J = 1.1, 7.7 Hz, 1H, CH Ar ); 7.21 (t, J = 7.7 Hz, 1H, CH Ar ); 7.16 (dt, J = 1.4, 7.4 Hz, 1H, CH Ar ); 7.12 (d, J = 7. 4 Hz, 1H, CH Ar ); 5.10 (dd, J = 2.1, 5.9 Hz, 1H, (CH(OH)); 3.07 (ddd, J = 3.6, 5.9, 9.3 Hz, 1H, aCH), 2.55 (ddd, J = 3.3, 9.7, 16.8 Hz, 1H, aCH a H b ), 2.52 (br s, 1H, OH), 2.33 (s, 3H, CH 3 ), 2.13 (ddd, J = 3.3, 8.…”

A stepwise lactol carbocyclisation to bridged ethers via a keto–acetal cascade

“…It was noted that the removal of alkene unsaturation through the formation of acetal 5 could still permit the overall desired formation of the bridged ether provided that conditions favouring the enolisation of the ketone also induced acetal cleavage to the 5-membered oxocarbenium species, giving potential for an intramolecular enolic cyclisation. Mindful of the wide application of titanium enolates in organic synthesis, 24 in which their chelating abilities are often crucial, TiCl 4 was selected for early study. To our delight, in the presence of TiCl 4 (2.2 equiv.…”

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

“…Furthermore, we also fully reported the aminoxylation reactions of titanium­(IV) enolates from several chiral platforms with TEMPO that produce α-oxygenated adducts in a highly stereocontrolled manner compatible with a biradical intermediate (eq 2 and 3 in Scheme ). Thus, the valence tautomery in titanium­(IV) enolates shown in Schemes and is well established, which is also compatible with the observed nucleophilic-like reactivity …”

“…Indeed, the very nature of these electronic configurations is, to a large extent, distinct: one corresponds to a closed shell electronic state, whereas the other has a marked open shell, delocalized biradical character, which requires an electron transfer from the organic ligand to the titanium metal. Therefore, the closed shell electronic configuration would be responsible for the classical nucleophilic reactivity observed for these titanium­(IV) enolates whereas the open shell might be the origin of the aforementioned biradical character and the basis for a new reacting paradigm: titanium­(IV) enolates can also participate in homolytic or radical additions (Scheme ).…”