Gregory C. Fu

Bio: Gregory C. Fu is an academic researcher from California Institute of Technology. The author has contributed to research in topics: Enantioselective synthesis & Alkyl. The author has an hindex of 35, co-authored 71 publications receiving 4900 citations. Previous affiliations of Gregory C. Fu include Massachusetts Institute of Technology.

A Convenient and General Method for Pd-Catalyzed Suzuki Cross-Couplings of Aryl Chlorides and Arylboronic Acids

Abstract: From only commercially available reagents a wide array of Suzuki cross-couplings of aryl chlorides with arylboronic acids can be effected in excellent yield [Eq. (a)]. This development provides a general solution to a long-standing limitation of this extremely powerful process-the poor reactivity of inexpensive and readily accessible aryl chlorides. dba=dibenzylideneacetone.

Asymmetric copper-catalyzed C-N cross-couplings induced by visible light.

Abstract: Despite a well-developed and growing body of work in copper catalysis, the potential of copper to serve as a photocatalyst remains underexplored. Here we describe a photoinduced copper-catalyzed method for coupling readily available racemic tertiary alkyl chloride electrophiles with amines to generate fully substituted stereocenters with high enantioselectivity. The reaction proceeds at –40°C under excitation by a blue light-emitting diode and benefits from the use of a single, Earth-abundant transition metal acting as both the photocatalyst and the source of asymmetric induction. An enantioconvergent mechanism transforms the racemic starting material into a single product enantiomer.

Transition metal-catalyzed alkyl-alkyl bond formation: Another dimension in cross-coupling chemistry.

Abstract: BACKGROUND The development of useful new methods for the construction of carbon-carbon bonds has had an impact on the many scientific disciplines (including materials science, biology, and chemistry) that use organic compounds. Tremendous progress has been made in the past several decades in the creation of bonds between sp 2 -hybridized carbons (e.g., aryl-aryl bonds), particularly through the use of transition metal catalysis. In contrast, until recently, advances in the development of general methods that form bonds between sp 3 -hybridized carbons (alkyl-alkyl bonds) had been rather limited. A variety of approaches, such as classical S N 2 reactions and transition metal catalysis, typically led to side reactions rather than the desired carbon-carbon bond formation. With transition metal catalysis, the unwanted but often facile β-hydride elimination of alkylmetal complexes presented a key impediment to efficient cross-coupling of alkyl electrophiles. In the case of many alkyl-alkyl bonds, there is an additional challenge beyond construction of the carbon-carbon bond itself: controlling the stereochemistry at one or both carbons of the new bond. It is important to control the stereochemistry of organic molecules because of its influence on properties such as biological activity. Each of these two challenges is difficult to solve individually; addressing them simultaneously is even more demanding. Until recently, the methods for achieving alkyl-alkyl bond formation were comparatively limited in scope, typically involving the use of unhindered (e.g., primary) electrophiles and unhindered, highly reactive nucleophiles (e.g., Grignard reagents, which have relatively poor functional group compatibility). With respect to enantioconvergent reactions, there were virtually no examples. ADVANCES In recent years, it has been established that, through the action of an appropriate transition metal catalyst, it is possible to achieve a broad range of alkyl-alkyl bond-forming processes; nickel-based catalysts have proved to be especially effective. With respect to the electrophilic coupling partner, a wide range of secondary alkyl halides are now suitable. This has enabled the development of enantioconvergent reactions of readily available racemic secondary electrophiles. In view of the abundance of tertiary stereocenters in organic molecules, this is a noteworthy advance in synthesis. With respect to the nucleophilic partner, alkylboron and alkylzinc reagents (Suzuki- and Negishi-type reactions, respectively) can now be used in a wide variety of alkyl-alkyl couplings, which greatly increases the utility of such processes, as these nucleophiles are more readily available and have much improved functional group compatibility relative to Grignard reagents. These new methods for alkyl-alkyl bond formation have been applied to the synthesis of natural products and other bioactive compounds. OUTLOOK A number of major challenges remain. For example, with regard to the electrophilic coupling partner, there is a need to develop general methods that are effective for tertiary alkyl halides, including enantioconvergent processes. With regard to the nucleophilic partner, there is a need to discover more versatile catalysts that can use a wide range of hindered (e.g., secondary and tertiary) alkylmetal reagents, as well as to achieve a broad spectrum of enantioconvergent couplings of racemic nucleophiles. These advances can enable the doubly stereoconvergent coupling of a racemic electrophile with a racemic nucleophile. The synthesis of alkyl-alkyl bonds is arguably the most important bond construction in organic synthesis. The ability to achieve this bond formation at will, as well as to control the product stereochemistry, would transform organic synthesis and empower the many scientists who use organic molecules. Recent work has provided evidence that transition metal catalysis can address this exciting challenge.

Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis

Abstract: An asymmetric decarboxylative Csp3–Csp2 cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide variety of naturally abundant α-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents.

Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes

Abstract: Classical methods for achieving nucleophilic substitutions of alkyl electrophiles (SN1 and SN2) have limited scope and are not generally amenable to enantioselective variants that employ readily available racemic electrophiles. Radical-based pathways catalyzed by chiral transition-metal complexes provide an attractive approach to addressing these limitations.

Palladium(II)-catalyzed C-H activation/C-C cross-coupling reactions: versatility and practicality.

Abstract: Pick your Pd partners: A number of catalytic systems have been developed for palladium-catalyzed CH activation/CC bond formation. Recent studies concerning the palladium(II)-catalyzed coupling of CH bonds with organometallic reagents through a PdII/Pd0 catalytic cycle are discussed (see scheme), and the versatility and practicality of this new mode of catalysis are presented. Unaddressed questions and the potential for development in the field are also addressed. In the past decade, palladium-catalyzed CH activation/CC bond-forming reactions have emerged as promising new catalytic transformations; however, development in this field is still at an early stage compared to the state of the art in cross-coupling reactions using aryl and alkyl halides. This Review begins with a brief introduction of four extensively investigated modes of catalysis for forming CC bonds from CH bonds: PdII/Pd0, PdII/PdIV, Pd0/PdII/PdIV, and Pd0/PdII catalysis. A more detailed discussion is then directed towards the recent development of palladium(II)-catalyzed coupling of CH bonds with organometallic reagents through a PdII/Pd0 catalytic cycle. Despite the progress made to date, improving the versatility and practicality of this new reaction remains a tremendous challenge.

Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize

Abstract: In 2010, Richard Heck, Ei-ichi Negishi, and Akira Suzuki joined the prestigious circle of Nobel Laureate chemists for their roles in discovering and developing highly practical methodologies for C-C bond construction. From their original contributions in the early 1970s the landscape of the strategies and methods of organic synthesis irreversibly changed for the modern chemist, both in academia and in industry. In this Review, we attempt to trace the historical origin of these powerful reactions, and outline the developments from the seminal discoveries leading to their eminent position as appreciated and applied today.

Palladium-Catalyzed Suzuki-Miyaura Cross-coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

Abstract: The cores of many types of polymers, ligands, natural products, and pharmaceuticals contain biaryl or substituted aromatic structures, and efficient methods of synthesizing these structures are crucial to the work of a broad spectrum of organic chemists. Recently, Pd-catalyzed carbon−carbon bond-forming processes, particularly the Suzuki−Miyaura cross-coupling reaction (SMC), have risen in popularity for this purpose. The SMC has many advantages over other methods for constructing these moieties, including mild conditions, high tolerance toward functional groups, the commercial availability and stability of its reagents, and the ease of handling and separating byproducts from its reaction mixtures. Until 1998, most catalysts for the SMC employed triarylphosphine ligands. More recently, new bulky and electron-rich phosphine ligands, which can dramatically improve the efficiency and selectivity of such cross-coupling reactions, have been introduced. In the course of our studies on carbon−nitrogen bond-formi...

Photoredox Catalysis in Organic Chemistry

Abstract: In recent years, photoredox catalysis has come to the forefront in organic chemistry as a powerful strategy for the activation of small molecules. In a general sense, these approaches rely on the ability of metal complexes and organic dyes to convert visible light into chemical energy by engaging in single-electron transfer with organic substrates, thereby generating reactive intermediates. In this Perspective, we highlight the unique ability of photoredox catalysis to expedite the development of completely new reaction mechanisms, with particular emphasis placed on multicatalytic strategies that enable the construction of challenging carbon–carbon and carbon–heteroatom bonds.

Dual Catalysis Strategies in Photochemical Synthesis

Abstract: The interaction between an electronically excited photocatalyst and an organic molecule can result in the genertion of a diverse array of reactive intermediates that can be manipulated in a variety of ways to result in synthetically useful bond constructions. This Review summarizes dual-catalyst strategies that have been applied to synthetic photochemistry. Mechanistically distinct modes of photocatalysis are discussed, including photoinduced electron transfer, hydrogen atom transfer, and energy transfer. We focus upon the cooperative interactions of photocatalysts with redox mediators, Lewis and Bronsted acids, organocatalysts, enzymes, and transition metal complexes.