Π-acid catalysis – challenges, advances, and opportunities

Π-acid catalysis is one of the last two decades′ most exciting developments in synthetic organic chemistry. Because of the mild conditions employed and high functional group tolerance, π-acid catalysis became a tool of choice for the selective activation of double and triple C−C bonds at the late stages of multistep syntheses. At the same time, owing to the simplicity of the reaction setup, it also provides an easy and atom-economic route towards a broad array of valuable precursors.

Traditionally, the field of π-acid catalysis has relied on complexes of Au(I) and Pt(II). These electron-rich cations are well-suited for the carbophilic activation of C−C multiple bonds. On the one hand, they are highly polarizable and hence can efficiently interact with the η₂-coordinated “soft” alkene or alkyne ligands. Yet, on the other hand, they are sufficiently electrophilic to render those ligands susceptible to nucleophilic attacks. While gold and platinum still maintain their privileged position in π-acid catalysis, the growing list of metals employable as π-acid catalysts now includes not only other noble elements (Pd, Rh, etc.), but also some earth-abundant ones, such as Cu, Zn, and even Al, providing cheaper alternatives for the precious metals.

The choice of ancillary ligands plays a crucial role in imparting an electrophilic character on metal centers for use as π-acid catalysts. New strong electron-withdrawing ancillary ligands were developed in search of better catalysts. A possible way to achieve this goal is by increasing the π-acidity of moderately π-acidic ligands, such as tertiary phosphines and N-heterocyclic carbenes (NHCs). In the present issue, two contributions - a communication by Manuel Alcarazo and a research article by Fumitoshi Shibahara - represent this endeavor.

Prof. Alcarazo is renowned for introducing the α-cationic phosphines and arsines as a novel class of highly π-acidic ancillary ligands for catalysis, mostly in Au(I) and Pt(II) systems. In recent years, his group has been active in developing asymmetric π-acid catalysis with chiral α-cationic phosphinates. A short communication presented in this issue describes the application of these unusual ancillary ligands for a highly enantioselective one-pot preparation of chiral C₂-symmetric [5]helicenes with two peripheral axial stereogenic centers. Asymmetric π-acid catalysis by Au(I) and Au(III) complexes is thoroughly addressed in a comprehensive review by Nitin Patil. Surprisingly, despite the prominent role of Au in π-acid catalysis in general, chiral gold catalysts have received much less attention. Prof. Patil's review aims at filling in this lacune and provides a retrospect of the significant developments in this area during the last 15 years.

A research article by Prof. Shibahara presents a different kind of π-acidic ancillary ligands. His group reports on a novel series of fused NHC ligands with electron-withdrawing groups: sulfoxide and sulfone. This combined experimental and theoretical study shows a straight correlation between the π-acidity of those ligands and the catalytic activity of the resulting Cu(I) complex in the hydroboration of alkynes. The imidazolopyridine-based carbenes used by Prof. Shibahara are mentioned in the context of fused polyaromatic NHC ligands used in π-acid catalysis in a review by Vincent César. Due to their inherent rigidity and great structural modularity, these heterobicyclic scaffolds have recently emerged as superior platforms for gold catalysis. In his review, Prof. César stresses explicitly the versatility of L-shaped bicyclic NHCs that allow easy construction of bifunctional and chiral Au(I) catalysts.

An additional way of rendering a metal center more electrophilic is by using the so-called Z-type ligands, the primary L−M σ-interaction in their complexes being of an inverse character relative to the traditional L-type ligands (M→L, rather than L→M). Significant progress in this direction was achieved during the last decade by François Gabbaï, who worked on different Sb-, Te-, and Ge-based Z-type ligands and applied their Au(I) and Pt(II) complexes as π-acid catalysts. A short communication presented herein describes the synthesis and reactivity of Au(I) complexes of Ge(IV)-based on neutral and cationic PGeP pincer ligands. In this study, Prof. Gabbaï reports an in situ formation of an intriguing dicationic [LGe(IV)-Au(I)]²⁺ species that acts as a highly reactive hydroamination catalyst.

Several important theoretical aspects of π-acid catalysts by Au(I) complexes are addressed in a review by William Unsworth. As those are often positively charged, the presence of a counterion is unavoidable. However, computational studies often neglect its effect on catalytic processes. Prof. Unsworth discusses how including anion effects in DFT calculations can theoretically rationalize the observed exo/endo or Markovnikov/Anti-Markovnikov selectivity in π-acid catalyzed reactions.

On a more practical note, applying π-acid catalysis can reduce the number of steps in synthetic protocols en route to pharmaceutically essential intermediates. A research article by Stephen K. Hashmi, where he demonstrates how π-acid catalysis can be utilized for an efficient protection group free one-pot synthesis of 2-acylidene-3-oxindoles, provides a prominent example of this approach. A review by Veronique Michelet revealed an additional practical facet of π-acid catalysis. She surveys various transition-metal catalyzed rearrangements and cycloisomerizations, resulting in fragrant compounds of interest to the perfume industry, with numerous transformations made possible by π-acid catalysts.

We hope that this special issue dedicated to π-acid catalysis will demonstrate its usefulness to the community of synthetic chemists and trigger inspiring ideas for further advances in this exciting and rapidly developing field.