https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

Once considered the 'holy grail' of organometallic chemistry, synthetically useful reactions employing C-H bond activation have increasingly been developed and applied to natural product and drug synthesis over the past decade. The ubiquity and relative low cost of hydrocarbons makes C-H bond functionalization an attractive alternative to classical C-C bond forming reactions such as cross-coupling, which require organohalides and organometallic reagents. In addition to providing an atom economical alternative to standard cross - coupling strategies, C-H bond functionalization also reduces the production of toxic by-products, thereby contributing to the growing field of reactions with decreased environmental impact. In the area of C-C bond forming reactions that proceed via a C-H activation mechanism, rhodium catalysts stand out for their functional group tolerance and wide range of synthetic utility. Over the course of the last decade, many Rh-catalyzed methods for heteroatom-directed C-H bond functionalization have been reported and will be the focus of this review. Material appearing in the literature prior to 2001 has been reviewed previously and will only be introduced as background when necessary. The synthesis of complex molecules from relatively simple precursors has long been a goal for many organic chemists. The ability to selectively functionalize a molecule with minimal pre-activation can streamline syntheses and expand the opportunities to explore the utility of complex molecules in areas ranging from the pharmaceutical industry to materials science. Indeed, the issue of selectivity is paramount in the development of all C-H bond functionalization methods. Several groups have developed elegant approaches towards achieving selectivity in molecules that possess many sterically and electronically similar C-H bonds. Many of these approaches are discussed in detail in the accompanying articles in this special issue of Chemical Reviews. One approach that has seen widespread success involves the use of a proximal heteroatom that serves as a directing group for the selective functionalization of a specific C-H bond. In a survey of examples of heteroatom-directed Rh catalysis, two mechanistically distinct reaction pathways are revealed. In one case, the heteroatom acts as a chelator to bind the Rh catalyst, facilitating reactivity at a proximal site. In this case, the formation of a five-membered metallacycle provides a favorable driving force in inducing reactivity at the desired location. In the other case, the heteroatom initially coordinates the Rh catalyst and then acts to stabilize the formation of a metal-carbon bond at a proximal site. A true test of the utility of a synthetic method is in its application to the synthesis of natural products or complex molecules. Several groups have demonstrated the applicability of C-H bond functionalization reactions towards complex molecule synthesis. Target-oriented synthesis provides a platform to test the effectiveness of a method in unique chemical and steric environments. In this respect, Rh-catalyzed methods for C-H bond functionalization stand out, with several syntheses being described in the literature that utilize C-H bond functionalization in a key step. These syntheses are highlighted following the discussion of the method they employ.

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Rhodium-Catalyzed C-C Bond Formation via Heteroatom-Directed C-H Bond Activation

Green Chemistry is a relatively new emerging field that strives to work at the molecular level to achieve sustainability. The field has received widespread interest in the past decade due to its ability to harness chemical innovation to meet environmental and economic goals simultaneously. Green Chemistry has a framework of a cohesive set of Twelve Principles, which have been systematically surveyed in this critical review. This article covers the concepts of design and the scientific philosophy of Green Chemistry with a set of illustrative examples. Future trends in Green Chemistry are discussed with the challenge of using the Principles as a cohesive design system (93 references).

Green Chemistry: Principles and Practice

N-Heterocyclic Carbenes in Late Transition Metal Catalysis

New cyclization reactions forming vinylcyclopropanes were developed wherein an alkenylrhodium(I) possessing a methoxy group at the allylic position as a potential leaving group acts as an allylic carbene equivalent. By this protocol, a vinylcyclopropane was installed in a complex cyclic structure in a single operation via successive multiple carbon−carbon bond formations.

Vinylcyclopropanation of Olefins via 3‐Methoxy‐1‐propenylrhodium(I).

α,β,γ,δ-Unsaturated imines are synthesized from N-sulfonyl-1,2,3-triazoles and allenes. Allenes are initially cyclopropanated by intermediate α-imino rhodium carbene complexes, and the resulting al...

Synthesis of α,β,γ,δ-Unsaturated Imines from N-Sulfonyl-1,2,3-triazoles and Allenes Through Rhodium-Catalyzed Cyclopropanation and Thermal Rearrangement.

A rhodium-catalyzed reaction of alkynyl oxiranes with arylboronic acids affords syn-configured α-allenols with high diastereoselectivity. The reaction is initiated by addition of an arylrhodium(I) species onto the alkyne moiety of the alkynyl oxirane. The resulting alkenylrhodium(I) intermediate undergoes β-oxygen elimination to open the oxirane ring in a syn-selective fashion. Protonolysis of the rhodium(I) alkoxide with arylboronic acid releases the corresponding α-allenol along with the rhodium(I) boronate, which undergoes β-aryl elimination to regenerate the arylrhodium(I) species. The utility of this method is demonstrated by an application to a concise synthesis of (±)-Boivinianin B.

Stereoselective Synthesis of syn‐Configured α‐Allenols by Rhodium‐Catalyzed Reaction of Alkynyl Oxiranes with Arylboronic Acids.

The reaction of alkyllithium with 2,6-xylyl isocyanide led to the trimerization of the isocyanide to afford an indole derivative. The anomalous reaction pattern provided inference about the structural features of the intermediate organolithium species.

Alkyllithium-Mediated Anomalous Trimerization of 2,6-Xylyl Isocyanide.

Treatment of isocyanates (I) with benzylic or allylic alcohols in the presence of a Pd-catalyst results in a cyclization and [1,3]-rearrangement sequence to give the title compounds.

Masahiro Murakami

Papers

Vinylcyclopropanation of Olefins via 3‐Methoxy‐1‐propenylrhodium(I).

Synthesis of α,β,γ,δ-Unsaturated Imines from N-Sulfonyl-1,2,3-triazoles and Allenes Through Rhodium-Catalyzed Cyclopropanation and Thermal Rearrangement.

Stereoselective Synthesis of syn‐Configured α‐Allenols by Rhodium‐Catalyzed Reaction of Alkynyl Oxiranes with Arylboronic Acids.

Alkyllithium-Mediated Anomalous Trimerization of 2,6-Xylyl Isocyanide.

Synthesis of 3,3-Disubstituted Oxindoles by Palladium-Catalyzed Tandem Reaction of 2-(Alkynyl)aryl Isocyanates with Benzylic Alcohols.