Unexpected Mild Protection of Alcohols as 2‐O‐THF and 2‐O‐THP Ethers Catalysed by Cp₂TiCl Reveal an Intriguing Role of the Solvent in the Single‐Electron Transfer Reaction

Abstract

A method for the conversion of primary, secondary and tertiary alcohols into the corresponding THF ethers at room temperature and primary and secondary alcohols into the corresponding THP ethers, has been developed using titanium(III) species generated from a catalytic amount of titanocene dichloride or (4R,5R)‐(–)‐2,2‐dimethyl‐α,α,α′,α′‐tetra(1‐naphthyl)‐1,3‐dioxolane‐4,5‐dimethanolatotitanium(IV) dichloride:acetonitrile adduct together with manganese(0) as a reductant and bromoform in THF or THP as the solvent. A radical mechanism is proposed for this transformation revealing an intriguing role of the solvent in the single‐electron transfer reactions catalysed by the low valent TiIII system.

Mild Epoxidation of Allylic Alcohols Catalyzed by Titanium(III) Complexes: Selectivity and Mechanism

“…Interestingly, when these latter reaction conditions were applied but THF was used as a solvent, compound (±)- 1a was only isolated in 3% yield (compare entries 4 and 6, Table 1) together with a 55% yield of the corresponding 2- O -tetrafuranyl ether. 10 In the light of previous reports, this change in the reactivity may be explained by any free coordination site in the catalyst being occupied by a THF molecule. 10,13 DME was a poorer solvent, generating (±)- 1a in moderate yield (entry 7, Table 1).…”

“…10 In the light of previous reports, this change in the reactivity may be explained by any free coordination site in the catalyst being occupied by a THF molecule. 10,13 DME was a poorer solvent, generating (±)- 1a in moderate yield (entry 7, Table 1).…”

“…To obtain a deeper insight into the reaction mechanisms, the enantioselectivity of the reaction was explored with Brintzinger’s ansa-titanocene catalyst A (17) and the chiral titanium complex B (10) (Figure 1), using geraniol as a model substrate. These complexes were reduced by manganese powder in dry and deoxygenated 1,4-dioxane to obtain a green solution of the corresponding Ti(III) species.…”

“…Recently, our research group has reported new mild reaction methodologies mediated by the Ti(III) species, which have allowed us the cyclopropanation of allylic alcohols, 8 transesterification of alcohols and phenols, 9 and the protection of alcohols as their 2- O -tetrahydrofuranyl and 2- O -tetrahydropyranyl ethers. 10…”

Tuning Acidity of Sulfonated Mesoporous Polymers (MP−SO3H) for Efficient Tetrahydropyranylation of Alcohols at Room Temperature

“…The chemoselective transformation of a target functional group in a multifunctional molecule is a challenging task for an organic chemist but this predicament can be turned away with the help of protecting groups . Protection of hydroxyl group plays a vital role in the multi‐step organic synthesis of complex molecules such as natural products and biologically active compounds . There are more than 150 hydroxyl protecting groups reported to date, but owing to its stability and chemical compatibility with various reaction conditions, 3,4‐dihydro‐2H‐pyran (DHP) is an attractive protecting group for the protection of alcohols.…”