The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Brønsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Brønsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Brønsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. The methodology gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (-)-Boivinianin A.

The combined use of a halogen bond (XB) donor with trimethylsilyl halide was found to be an efficient cocatalytic system for the direct dehydroxylative coupling reaction of alcohol with various nucleophiles, such as allyltrimethylsilane and trimethylcyanide, to give the corresponding adduct in moderate to excellent yields. Detailed control experiments and mechanistic studies revealed that the XB interaction was crucial for the reaction. The application of this coupling reaction is also described.

The heterodimerizing self-assembly between a phosphoric acid catalyst and a carboxylic acid has recently been established as a new activation mode in Brønsted acid catalysis. In this article, we present a comprehensive mechanistic investigation on this activation principle, which eventually led to its elucidation. Detailed studies are reported, including computational investigations on the supramolecular heterodimer, kinetic studies on the catalytic cycle, and a thorough analysis of transition states by DFT calculations for the rationalization of the catalyst structure-selectivity relationship. On the basis of these investigations, we developed a kinetic resolution of racemic epoxides, which proceeds with high selectivity (up to s = 93), giving the unreacted epoxides and the corresponding protected 1,2-diols in high enantiopurity. Moreover, this approach could be advanced to an unprecedented stereodivergent resolution of racemic α-chiral carboxylic acids, thus providing access to a variety of enantiopure nonsteroidal anti-inflammatory drugs and to α-amino acid derivatives.

In recent years, several organocatalytic asymmetric hydroarylations of activated, electron-poor olefins with activated, electron-rich arenes have been described. In contrast, only a few approaches that can handle unactivated, electronically neutral olefins have been reported and invariably require transition metal catalysts. Here we show how an efficient and highly enantioselective catalytic asymmetric intramolecular hydroarylation of aliphatic and aromatic olefins with indoles can be realized using strong and confined IDPi Brønsted acid catalysts. This unprecedented transformation is enabled by tertiary carbocation formation and establishes quaternary stereogenic centers in excellent enantioselectivity and with a broad substrate scope that includes an aliphatic iodide, an azide, and an alkyl boronate, which can be further elaborated into bioactive molecules.