Fuk Yee Kwong

Organocatalysis in Cross-Coupling: DMEDA-Catalyzed Direct C−H Arylation of Unactivated Benzene

A striking breakthrough to the frame of traditional cross-couplings/C-H functionalizations using an organocatalyst remains unprecedented. We uncovered a conceptually different approach toward the biaryl syntheses by using DMEDA as the catalyst to promote the direct C-H arylation of unactivated benzene in the presence of potassium tert-butoxide. The arylation of unactivated benzene with aryl iodides, or aryl bromides and even chlorides under the assistance of an iodo-group, could simply take place at 80 °C. The new methodology presumably involves an aryl radical anion as an intermediate. This finding offers an option toward establishing a new horizon for direct C-H/cross-coupling reactions.

Palladium‐Catalyzed Cross‐Dehydrogenative Functionalization of C(sp2)H Bonds

The catalytic cross-dehydrogenative coupling (CDC) reaction has received intense attention in recent years. The attractive feature of this coupling process is the formation of a C-C bond from two C-H moieties under oxidative conditions. In this Focus Review, recent advances in the palladium-catalyzed CDC reactions of C(sp(2) )-H bond are summarized, with a focus on the period from 2011 to early 2013.

Palladium-catalyzed cross-coupling reactions of aryl mesylates

Palladium-catalyzed cross-coupling reactions are state-of-the art methods for synthesis of many important compounds. The development of the use of the phenol-derived sulfonated hydroxyl group in the coupling reactions is highly attractive as the hydroxyl group is commonly present in organic compounds and they are versatile alternatives to aryl halides in cross-coupling reactions. In this tutorial review, we summarize the current development of palladium-catalyzed cross-coupling reactions of aryl mesylates.

Palladium-Catalyzed Oxidative C–H Bond Coupling of Steered Acetanilides and Aldehydes: A Facile Access to ortho-Acylacetanilides

A palladium-catalyzed oxidative C-H bond functionalization/ortho-acylation of acetanilides using easily accessible aldehyde as the acyl source is described. In the presence of a Pd(TFA)(2) catalyst and tert-butylhydroperoxide at 90 °C in general, an array of ortho-acylacetanilides can be afforded in good yields.

Palladium-Catalyzed Amination of Aryl Mesylates†

Palladium-catalyzed C(sp2) N bond-forming reactions have evolved into a highly versatile and synthetically attractive transformation in targeting pharmaceutically useful intermediates. Since the discovery of the first catalytic amination method, efforts have been made toward increasing the reaction efficacy. Notable ligands, such as tBu3P, [4] Beller and co-workers( PAP, Buchwald and co-workers( biaryl phosphines, Hartwig and co-workers( Q-Phos, and Verkade and co-workers( amino phosphine (Figure 1) provide excellent catalytic activity in the cross-coupling of aryl halides (especially aryl chlorides). X-Phos, in particular, is effective in the handling of aryl tosylate/benzenesulfonate substrates in coupling reactions.

Suzuki−Miyaura Coupling of Aryl Tosylates Catalyzed by an Array of Indolyl Phosphine−Palladium Catalysts

A family of indolyl phosphine ligands was applied to Suzuki-Miyaura cross-coupling of aryl tosylates. Catalyst loading can be reduced to 0.2 mol % for coupling of nonactivated aryl tosylate. A challenging example for room temperature coupling is realized. The scope of this highly active Pd/L2 system can be extended to other boron nucleophiles, including trifluoroborate salts and boronate esters. The ligand structural comparisons toward the reactivity in tosylate couplings are also described.

Intramolecular Direct C–H Bond Arylation from Aryl Chlorides: A Transition-Metal-Free Approach for Facile Access of Phenanthridines

A C-H arylation with aryl chloride is made viable through a transition-metal-free approach. In the presence of a simple diol associating with KOt-Bu, various phenanthridine derivatives can be conveniently accessed. In particular, only 10 mol % of simple and inexpensive ethylene glycol is required for this protocol. These results represent the first general examples of aryl chloride/C-H coupling under transition-metal-free conditions.

Advances and Applications in Organocatalytic Asymmetric aza‐Michael Addition

The stereocontrolled construction of chiral carbon–carbon bonds and carbon–heteroatom bonds are topics of paramount importance in modern organic synthesis. The importance has been driven predominantly by optically active compounds in natural products and pharmaceuticals. The success of asymmetric organocatalysis can be attributed to the advantages of their availability and their capacity to perform asymmetric transformations in a metal-free environment, under mild and non-inert reaction conditions. Asymmetric organocatalysis, using small chiral organic molecules as enantioselective catalysts, has experienced an impressive growth and is now considered the “third pillar” of enantioselective catalysis together with biocatalysis and metal catalysis. Among the great variety of organocatalytic asymmetric transformations, Michael additions occupy a very important position and have received widespread attention for accessing a variety of chiral synthetically useful building blocks. In particular, the Michael addition of nitrogen-based nucleophiles to a,b-unsaturated carbonyl systems, also termed the aza-Michael reaction, represents an especially interesting variant since it is a versatile method for constructing a new C N bond and constitutes; an important step in the synthesis of bioactive natural compounds. During the past decade, a number of elegant organocatalysts have been developed for enantiocontrol in a large variety of reactions. Accordingly, the organocatalytic asymmetric aza-Michael addition has been a very active field of research, the previous progress of which has also been the subject to some excellent reviews. The majority of organocatalytic reactions are amine catalystbased and proceed via enamine or iminium intermediates, or the amine acts as a base. Therefore, a possible competition between the catalyst and the nitrogen-based nucleophile exists in the organocatalytic aza-Michael addition. This could compromise the enantioselectivity of the reaction and remains as one of the difficulties in developing organocatalytic asymmetric aza-Michael addition. Consequently, the appropriate choices of the nitrogen-based nucleophile and the catalyst system represent a critical factor in the organocatalytic asymmetric azaMichael addition. Encouragingly, significant progress has been made in the past several years towards achieving organocatalytic asymmetric aza-Michael additions during the rapid development of asymmetric organocatalysis. Many new substrates have been applied accordingly in this transformation, together with the new approaches developed for the purpose of targetand diversity-oriented asymmetric synthesis. Based on the comprehensive work of Enders, the process made in organocatalytic asymmetric aza-Michael addition between 2010 and early 2012 are surveyed in this review. The review is also organized according to the catalyst system used.

A Mild and Efficient Palladium-Catalyzed Cyanation of Aryl Chlorides with K4[Fe(CN)6]

An efficient palladium-catalyzed cyanation of aryl chlorides is established. In the presence of a highly effective Pd/CM-phos catalyst, cyanation of aryl chlorides proceeds at 70 °C in general, which is the mildest reaction temperature achieved so far for this process. Common functional groups such as keto, aldehyde, ester, nitrile and -NH(2), and heterocyclic coupling partners including N-H indoles are well tolerated. Moreover, a sterically hindered nonactivated ortho,ortho-disubstituted electrophile is shown to be a feasible coupling partner in cyanation.

Palladium−Indolylphosphine-Catalyzed Hiyama Cross-Coupling of Aryl Mesylates

Aryl mesylates are found to be applicable as electrophiles in organosilicon-mediated coupling reactions. The catalyst system comprising 2 mol % of Pd(OAc)(2) and CM-phos supporting ligand is highly effective in catalyzing Hiyama cross-coupling of various aryl and heteroaryl mesylates. Interesting acid additive effects show that the presence of 0.25-0.50 equiv of acetic acid efficiently suppresses the mesylate decomposition and generally promotes the coupling product yields.