Brønsted Acid‐Catalysed Dehydrative Substitution Reactions of Alcohols

Abstract

Dedicatedtothe memory of Professor Jonathan M. J. Williams, my mentor and friend.

Zirconium-catalysed direct substitution of alcohols: enhancing the selectivity by kinetic analysis

“…10 Catalytic nucleophilic substitution is commonly carried out by using a borrowing hydrogen strategy, 11 transition metal-catalysed substitution of allylic alcohols via π-allyl intermediates 12 or direct substitution using Lewis basic [13][14][15] or Lewis acidic catalysts. 2,[16][17][18][19][20][21][22] In addition, the use of protic acids has been explored to a lesser extent [23][24][25][26][27] Tetravalent metal complexes with fluoroalkylsulfonate ligands constitute an interesting class of water-stable Lewis acidic catalysts for a variety of transformations. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Despite this, this catalyst class is hardly represented in the context of dehydrative substitution of alcohols in contrast to its trivalent (and bivalent) counterparts.…”

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

“…Friedel-Crafts alkylation of primary aliphatic alcohols Primary aliphatic alcohols generally do not undergo Friedel-Crafts reactions, [3][4][5][6] except for some examples with methanol and ethanol under extreme conditions, e.g., using high temperatures (300 C-400 C) with zeolites as promoters. 87,88 However, the reactivity with epoxides clearly indicates this is possible using the TfOH/ HFIP reaction system.…”

“…Epoxides and primary aliphatic alcohols both represent important building blocks in synthetic chemistry, 1 the former especially serving as a gateway to densely functionalized molecules in medicinal chemistry, crop science, and material science. 2 In principle, the intermolecular Friedel-Crafts reaction would represent an ideal way to form C-C bonds between arenes and epoxides or primary aliphatic alcohols, [3][4][5][6] since it would prevent pre-activation steps of the substrates and produce no stoichiometric waste beyond water, but this type of reactivity remains challenging in both cases:…”

Oxetan-3-ols as 1,2-bis-Electrophiles in a Brønsted-Acid-Catalyzed Synthesis of 1,4-Dioxanes

“…Instead, we investigated strong Brønsted acids. 21 Using catalytic TfOH, we were delighted to obtain dioxane 2 in 42% yield (entry 2). A switch to toluene as solvent and an increase in catalyst loading to 10 mol % further improved the yield (entries 3–5).…”