Alan Ford,† Hugues Miel, Aoife Ring,† Catherine N. Slattery,† Anita R. Maguire,*,†,‡ and M. Anthony McKervey* †Department of Chemistry and ‡School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland Almac Discovery Ltd., David Keir Building, Stranmillis Road, Belfast BT9 5AG, United Kingdom Almac Sciences Ltd., Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, United Kingdom

Modern Organic Synthesis with α-Diazocarbonyl Compounds

The present review offers an overview of the current approaches for the photochemical and photocatalytic generation of reactive intermediates and their application in the formation of carbon–carbon bonds. Valuable synthetic targets are accessible, including arylation processes, formation of both carbo- and heterocycles, alpha- and beta-functionalization of carbonyls, and addition reactions onto double and triple bonds. According to the recent advancements in the field of visible/solar light catalysis, a significant part of the literature reported herein involves radical ions and radicals as key intermediates, with particular attention to the most recent examples. Synthetic application of carbenes, biradicals/radical pairs and carbocations have been also reported.

Carbon-Carbon Bond Forming Reactions via Photogenerated Intermediates.

Transition-metal-catalyzed cross-coupling reactions have been well-established as indispensable tools in modern organic synthesis. One of the major research goals in cross-coupling area is expanding the scope of the coupling partners. In the past decade, diazo compounds (or their precursors N-tosylhydrazones) have emerged as nucleophilic cross-coupling partners in C–C single bond or C═C double bond formations in transition-metal-catalyzed reactions. This type of coupling reaction involves the following general steps. First, the organometallic species is generated by various processes, including oxidative addition, transmetalation, cyclization, C–C bond cleavage, and C–H bond activation. Subsequently, the organometallic species reacts with the diazo substrate to generate metal carbene intermediate, which undergoes rapid migratory insertion to form a C–C bond. The new organometallic species generated from migratory insertion may undergo various transformations. This type of carbene-based coupling has proven...

Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion

Cofactor-mimetic aerobic oxidation has conceptually merged with catalysis of syngas reactions to form a wide range of Markovnikov-selective olefin radical hydrofunctionalizations. We cover the development of the field and review contributions to reaction invention, mechanism, and application to complex molecule synthesis. We also provide a mechanistic framework for understanding this compendium of radical reactions.

/pdf/mn-fe-and-co-catalyzed-radical-hydrofunctionalizations-of-3ukqn8iif4.pdf

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

The functionalization of C-H bonds has created new approaches to preparing organic molecules by enabling new strategic "disconnections" during the planning of a synthetic route. Such functionalizations also have created the ability to derivatize complex molecules by modifying one or more of the many C-H bonds. For these reasons, researchers are developing new types of functionalization reactions of C-H bonds and new applications of these processes. These C-H bond functionalization reactions can be divided into two general classes: those directed by coordination to an existing functional group prior to the cleavage of the C-H bond (directed) and those occurring without coordination prior to cleavage of the C-H bond (undirected). The undirected functionalizations of C-H bonds are much less common and more challenging to develop than the directed reactions. This outlook will focus on undirected C-H bond functionalization, as well as related reactions that occur by a noncovalent association of the catalyst prior to C-H bond cleavage. The inherent challenges of conducting undirected functionalizations of C-H bonds and the methods for undirected functionalization that are being developed will be presented, along with the factors that govern selectivity in these reactions. Finally, this outlook discusses future directions for research on undirected C-H functionalization, with an emphasis on the limitations that must be overcome if this type of methodology is to become widely used in academia and in industry.

http://pubs.acs.org/doi/pdf/10.1021/acscentsci.6b00032

Undirected, Homogeneous C-H Bond Functionalization: Challenges and Opportunities.

Catalytic asymmetric C-H insertion reactions of α-diazocarbonyl compounds

Asymmetric copper-catalysed intramolecular C–H insertion reactions of a series of α-diazo-β-keto sulfones are reported. Enantioselectivities of up to 82% ee were achieved in moderate to good yield. These results represent the highest level of enantiocontrol achieved to date for a copper-catalysed cyclopentanone synthesis via C–H insertion.

Catherine N. Slattery

Papers

Modern Organic Synthesis with α-Diazocarbonyl Compounds

Catalytic asymmetric C-H insertion reactions of α-diazocarbonyl compounds

Asymmetric copper-catalysed intramolecular C–H insertion reactions of α-diazo-β-keto sulfones

Catalyst and substituent effects on the rhodium(II)-catalysed intramolecular Buchner reaction

Catalyst, additive and counterion effects on the efficiency and enantioselectivity of copper-catalysed C–H insertion reactions of α-diazosulfones