Enhancing the Regioselectivity of B(C₆F₅)₃-Catalyzed Epoxide Alcoholysis Reactions Using Hydrogen-Bond Acceptors

Abstract

Epoxide alcoholysis is extensively employed in the synthesis of polymers and chemical intermediates, and it generally requires an acid catalyst for high rates and selectivity. Tris­(pentafluorophenyl)­borane [B­(C6F5)3] is among few catalysts that are selective to primary alcohol products of terminal aliphatic epoxides that do not possess any directing groups. We have previously observed that under many conditions, the reaction regioselectivity increases with conversion. Here, we confirm a prediction from our earlier computational model, and we experimentally demonstrate that this increase is due to a selectivity-enhancing role of the reaction products. We then show that deliberate addition of catalytic amounts of certain diols increases the reaction regioselectivity. Cis-1,2 or 1,3-diols are required to enhance selectivity, consistent with a mechanism where extended hydrogen-bonding networks preferentially organize the reactants. This work presents a route to tune regioselectivity without altering the catalyst backbone and provides another example of the role of H-bonding networks in reactions taking place in protic media.

Strong Influence of the Nucleophile on the Rate and Selectivity of 1,2-Epoxyoctane Ring Opening Catalyzed by Tris(pentafluorophenyl)borane, B(C6F5)3

“…Parameters VI and VII, which account for the second-generation RO reactions by P1 or P2 that occur at high epoxide conversion, indicated that P1 is more reactive than 1Prop, while P2 is less reactive than 1Prop as a nucleophile. Stated otherwise, 1Prop-derived P1 preferentially forms larger oligomers, consistent with Figure and our companion work . Thus, in the absence of oligomerization, the selectivity to P1 would be even higher than observed experimentally in the 1Prop system.…”

“…The results here show that a model with only a Lewis acid pathway is not sufficient to describe the system because the pronounced dependence of product selectivity on reaction conditions (e.g., water concentration) that we have observed is not possible to be captured by any model that uses a single kinetically relevant pathway. In contrast, our triple-pathway mechanism is robust enough to capture reactivity trends across a wide range of conditions and to provide hypotheses about deliberately added species that could beneficially influence the reaction selectivity, as we discuss in our companion manuscript …”

“…As detailed in our companion paper by Bhagat et al., oligomerization reactions have the effect of decreasing product selectivity as a function of conversion in the 1Prop system, requiring that another catalytic species be responsible for the increase in selectivity with conversion. Bhagat et al also show that the addition of catalytic amounts of cis -1,2 and 1,3-diols significantly enhances regioselectivity and changes the dependence of regioselectivity on conversion . This is additional experimental confirmation of the role of water-mediated catalysis in epoxide RO, which is supported by theoretical calculations that show that these diols stabilize the incoming nucleophile (Figure ) and provide a lower energy barrier, higher regioselectivity pathway for RO.…”

“…Developed in the early 1960s, tris­(pentafluorophenyl)­borane, B­(C 6 F 5 ) 3 , also known as BCF, has been shown to be a strong Lewis acid with high thermal stability, water tolerance, and chemical versatility. BCF and its derivatives have been studied for a variety of applications, such as co-catalysts for homogenous Ziegler–Natta olefin polymerization chemistry, components in frustrated Lewis pair (FLP) hydrogenation catalysis, and as catalysts or initiators in many organic transformations. − Of particular industrial relevance is the role of BCF in the catalytic, regioselective ring-opening (RO) polymerization of epoxides, as these reactions form key polyether polyol intermediates for the production of polyurethanes. , This and similar aryl boranes are believed to be the only catalysts known to the open literature that are capable of high levels of primary alcohol selectivity for the RO of aliphatic epoxides. − …”

Catalytic Regioselective Isomerization of 2,2‐Disubstituted Oxetanes to Homoallylic Alcohols

“…We then tested abulky Lewis acid, namely B(C 6 F 5 ) 3 . [22] Gratifyingly,t he reaction in dichloromethane afforded the homoallylic alcohol with excellent yield (82 %) and selectivity (3a/4a:98:2, entry 8). With this result in hand, we performed asolvent screening.…”