A Guide to Directing Group Removal: 8-Aminoquinoline

The use of directing groups allows high levels of selectivity to be achieved in transition metal-catalyzed transformations. Efficient removal of these auxiliaries after successful functionalization, however, can be very challenging. This review provides a critical overview of strategies used for removal of Daugulis’ 8-aminoquinoline (2005–2020), one of the most widely used N,N-bidentate directing groups. The limitations of these strategies are discussed and alternative approaches are suggested for challenging substrates. Our aim is to provide a comprehensive end-users’ guide for chemists in academia and industry who want to harness the synthetic power of directing groups—and be able to remove them from their final products.     

Visible-light photoredox catalysis

In the last few years, visible-light initiated organic transformations have attracted increasing attention. The development of visible-light-promoted photocatalytic reactions, which enable rapid and efficient synthesis of fine chemicals, is highly desirable from the viewpoint of cost, safety, availability, and environmental friendliness. In this Minireview, recent advances made in this fast developing area of research are discussed.     

Gold catalysis: phenol synthesis in the presence of functional groups

The effect of different substituents, such as bromo, chloromethyl, hydroxymethyl, formyl, acetyl, carboxy, and acylated hydroxymethyl and ammonium groups, on the furan ring of substrates in gold-catalyzed phenol synthesis has been investigated. The furan ring was also replaced by different heterocycles, such as pyrroles, thiophenes, oxazoles, and a 2,4-dimethoxyphenyl group; gold catalysis then delivered no phenols, but occasionally other products were obtained. [Ru(3)(CO)(12)] also catalyzed the conversion of 1 at a low rate, [Os(3)(CO)(12)] failed as a catalyst, and with [Co(2)(CO)(8)] the alkyne complex 19 can be obtained, it does not lead to any phenol but reacts with norbornene to give the product of a Pauson-Khand reaction. Efforts to prepare vinylidene complexes of 1 provided the only evidence for these species; in the presence of a phosphane ligand with ruthenium an interesting deoxygenation to 22 was observed. The phenol 2 c was converted to the allyl ether, a building block for para-Claisen rearrangements, and to the aryl triflate, a building block for cross-coupling reactions.     

Gold in total synthesis: alkynes as carbonyl surrogates

Fields of gold: Recent developments in the field of gold catalysis, using an alkyne as a carbonyl equivalent is becoming an important chemical transformation, thus providing flexibility in synthetic planning of complex and sensitive natural products. Understanding of the reaction and new catalyst designs are providing new conditions that are amenable for late-stage synthetic intermediates.     

Gold catalysis: deuterated substrates as the key for an experimental insight into the mechanism and selectivity of the phenol synthesis

The second phase of the gold-catalyzed phenol synthesis, the ring opening of the intermediate arene oxide, follows general acid catalysis. The product selectivity is determined by the substrate only and can be explained by the stability of the intermediate arenium ions. Thus, even remote substitutents can be used to control the chemoselectivity of the overall reaction by electronic influences and their influence is stronger than the steric influence of neighboring substituents. This is supported by quantum chemical calculations of the intermediates. The lack of exchange of deuterium labels excludes even equilibria with acetylide or vinylidene intermediates and the observed deuterium distribution in the final products is in accord with the NIH-shift reaction. In addition, these findings now explain previously obtained results.     

A 3,4‐trans‐Fused Cyclic Protecting Group Facilitates α‐Selective Catalytic Synthesis of 2‐Deoxyglycosides

A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high α‐selectivity and yields (77–97 %) using a trans‐fused cyclic 3,4‐O‐disiloxane protecting group and TsOH?H₂O (1 mol %) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side‐chain conformation augments the selectivity.     

Lewis base catalysis in organic synthesis

The legacy of Gilbert Newton Lewis (1875–1946) pervades the lexicon of chemical bonding and reactivity. The power of his concept of donor–acceptor bonding is evident in the eponymous foundations of electron‐pair acceptors (Lewis acids) and donors (Lewis bases). Lewis recognized that acids are not restricted to those substances that contain hydrogen (Brønsted acids), and helped overthrow the “modern cult of the proton”. His discovery ushered in the use of Lewis acids as reagents and catalysts for organic reactions. However, in recent years, the recognition that Lewis bases can also serve in this capacity has grown enormously. Most importantly, it has become increasingly apparent that the behavior of Lewis bases as agents for promoting chemical reactions is not merely as an electronic complement of the cognate Lewis acids: in fact Lewis bases are capable of enhancing both the electrophilic and nucleophilic character of molecules to which they are bound. This diversity of behavior leads to a remarkable versatility for the catalysis of reactions by Lewis bases.     

Accessing Remote meta‐ and para‐C(sp2)−H Bonds with Covalently Attached Directing Groups

Directing group assisted ortho‐C?H activation has been known for the last few decades. In contrast, extending the same approach to achieve activation of the distal meta‐ and para‐C?H bonds in aromatic molecules remained elusive for a long time. The main challenge is the conception of a macrocyclic transition state, which is needed to anchor the metal catalyst close to the target bond. Judicious modification of the chain length, the tether linkage, and the nature of the catalyst‐coordinating donor atom has led to a number of successful studies in the last few years. This Review compiles the significant achievements made in this field of both meta‐ and para‐selectivity using covalently attached directing groups, which are systematically classified on the basis of their mode of covalent attachment to the substrate as well as their chemical nature. This Review aims to create a more heuristic approach for recognizing the suitability of the directing groups for use in future organic transformations.