Brønsted Acid-Catalyzed Reactions of Trifluoroborate Salts with Benzhydryl Alcohols

Abstract

Brønsted acid-catalyzed carbon-carbon bond forming methodology using potassium alkynyl- and alkenyltrifluoroborate salts has been developed. Organotrifluoroborates react with benzhydryl alcohols to afford a broad range of alkynes and alkenes in good to excellent yields. This protocol features good atom economy because organotrifluoroborate salts and alcohols react in a 1:1 ratio. Furthermore, a variety of unprotected functional groups were tolerated under the developed conditions, including amide, aldehyde, free hydroxyl, and carboxylic acid.

Brønsted Acid-Catalyzed Direct Substitution of 2-Ethoxytetrahydrofuran with Trifluoroborate Salts

“…Previously, we discovered that tetrafluoroboric acid (HBF4) is an effective catalyst for the reactions of trifluoroborate salts [4,5]. To investigate the efficiency of the HBF4 as a Brønsted acidcatalyst towards the substitution of 2-ethoxytetrahydrofuran, we first looked at using unsubstituted potassium phenylacetylenetrifluoroborate salt (S1) as a model substrate (Table 1).…”

“…To our delight, product 1a was obtained in an excellent 92% yield ( We found that the substitution was achieved with 75% yield of the desired product 1a when a slight excess of 1.1 equivalents of both the organotrifluoroborate (S1) and HBF 4 acid catalyst were used (Table 1, entry 1). Attempts to use an alternative acid such as trifluoroacetic acid, which has a pK a similar to that of HBF 4 , only resulted in trace amounts of product formation (Table 1, entry 2). Our previous studies indicated that increasing the amounts of trifluoroborate salt and HBF 4¨O Et 2 to 1.5 equivalents resulted in a higher yield for the alkynylation of ketals [5].…”

“…To our delight, product 1a was obtained in an excellent 92% yield (Table 1, entry 3). Other reaction conditions, such as reaction temperature and solvent, were not directly explored since both conditions were already extensively studied in our previously described set of novel Brønsted acid-catalyzed reactions [4,5].…”

“…In addition to phenylacetylenetrifluoroborates, hexynyltrifluoroborate salt reacted with 2-ethoxytetrahydrofuran to afford product 1h in 64% yield. as reaction temperature and solvent, were not directly explored since both conditions were already extensively studied in our previously described set of novel Brønsted acid-catalyzed reactions [4,5].…”

“…Direct substitution at the 2-position of 2-ethoxytetrahydrofuran occurs in the presence of a Brønsted acid catalyst. Recently, our group has discovered that Brønsted acid-catalyzed reactions of benzhydryl alcohols [4] and acetals/ketals [5] with organotrifluoroborates proceed with excellent functional group tolerance. Previously, organotrifluoroborate salts have been shown to act as shelf-stable equivalents of boronic acids [6].…”