Demystifying Cp₂Ti(H)Cl and Its Enigmatic Role in the Reactions of Epoxides with Cp₂TiCl

Abstract

The role of Cp2Ti(H)Cl in the reactions of Cp2TiCl with trisubstituted epoxides has been investigated in a combined experimental and computational study. Although Cp2Ti(H)Cl has generally been regarded as a robust species, its decomposition to Cp2TiCl and molecular hydrogen was found to be exothermic (ΔG = −11 kcal/mol when the effects of THF solvation are considered). In laboratory studies, Cp2Ti(H)Cl was generated using the reaction of 1,2-epoxy-1-methylcyclohexane with Cp2TiCl as a model. Rapid evolution of hydrogen gas was demonstrated, indicating that Cp2Ti(H)Cl is indeed a thermally unstable molecule, which undergoes intermolecular reductive elimination of hydrogen under the reaction conditions. The stoichiometry of the reaction (Cp2TiCl:epoxide = 1:1) and the quantity of hydrogen produced (1 mole per 2 moles of epoxide) is consistent with this assertion. The diminished yield of allylic alcohol from these reactions under the conditions of protic versus aprotic catalysis can be understood in terms of the predominant titanium(III) present in solution. Under the conditions of protic catalysis, Cp2TiCl complexes with collidine hydrochloride and the titanium(III) center is less available for “cross-disproportionation” with carbon-centered radicals; this leads to by-products from radical capture by hydrogen atom transfer, resulting in a saturated alcohol.

Four Mechanistic Mysteries: The Benefits of Writing a Critical Review

“…The second equivalent of Cp 2 TiCl would be unnecessary, since half of the reagent would be converted into Cp 2 Ti(H)Cl, which then decomposes, regenerating Cp 2 TiCl. We demonstrated this in the laboratory [16] …”

“…Theplot thickens!Details of the calculations have been published elsewhere. [16] At this point, we could not resist going into the lab to have ah ands-on look at this chemistry.O ne of our collaborators, Kendra Dewese prepared the simple model epoxide 11 and added it to asolution of Cp 2 TiCl in THF.During the addition, she observed vigorous gas evolution!T he gas was confirmed to be hydrogen by GC-MS.Even better,using agas burette it was possible to the measure the amount of hydrogen evolved, which was very close to the predicted 0.5 mol per mol of epoxide consumed in Scheme 4and Equation (4). Hydrolysis of the titanium alkoxide product and characterization of the organic product confirmed that allylic alcohols 14 a and 14 b were formed in a5:1 ratio.…”

“…We demonstrated this in the laboratory. [16] Mystery 2: The Riddle of Reversing Selectivities Ther eactions of b,g-epoxy alcohols with Cp 2 TiCl differ from those of unsubstituted epoxides in three ways.F irst, the site selectivity for epoxide ring-opening is different. [18] Treatment of trimethysilyl-protected alcohol 15 a with Cp 2 TiCl in the presence of tert-butyl thiol affords 16,which results from predominant opening at C-3, as shown in Scheme 5.…”

Cp2TiIIICl Catalysis in a New Light

“…[22] Under catalytic conditions, Ti III species are mainly present as complex 3 in the presence of excess collindine•HCl (Scheme 1, a). [23] Cp 2 Ti III Cl can also be synthesized via electrochemical reduction of Cp 2 TiCl 2 . [24] Recently, a novel photogeneration of Cp 2 Ti III Cl with the aid of a photocatalyst was reported by the Gansäuer group and Shi group (Scheme 1, b).…”

Visible-light-driven spirocyclization of epoxides via dual titanocene and photoredox catalysis

“…[13][14][15][16] The key to success was the formation of a stable complex A in reactions while decreasing the concentration of active Cp 2 Ti III Cl. 17,18 We were interested in the radical opening/cyclization reaction of epoxides which has attracted considerable attention from the synthetic community and has been used numerous times in the synthesis of natural products. 19,20 Nevertheless, this reaction required stoichiometric metallic reductants and proceeded slowly particularly with sterically hindered substrates even with high catalyst loading.…”