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

Development of new cycloaddition reactions of conjugated allenes catalyzed by transition metal complexes is described. In the first place, the synthesis and structures of vinylallene-rhodium complexes were investigated. (Vinylallene) rhodium complexes of three kinds of coordination modes, that is, η2-coordination, η4-coordination, and planar σ2-coordination, were selectively synthesized by facile ligand substitution of the Wilkinson's complex with vinylallenes of different substitution patterns. The endo-exo isomerization observed with the η4-complex suggested a considerable contribution from the metallacyclic form. This structural study led us to develop a new carbonylative [4+1] cycloaddition reaction of vinylallenes, which was further extended to a highly enantioselective synthesis of 2- (alkylidene) cyclopentenone. Next, the intermolecular directed [4+2] cycloaddition of a vinylallene with an ordinary 1, 3-diene was achieved by the use of a palladium (0) catalyst. An excellent specificity observed between the vinylallene geometries and the cycloadduct stereostructures was explained by assuming a mechanism involving a (π-allyl) palladium intermediate. The iridium-catalyzed carbonylative [5+1] cycloaddition reaction was also developed, wherein a six-membered cyclohexenone skeleton was assembled from allenylcyclopropane and carbon monoxide.

New Cycloaddition Reactions of Conjugated Allenes Catalyzed by Transition Metal Complexes

Background: Two recent randomized controlled trials demonstrated the beneficial effects of subcutaneous drainage in preventing incisional surgical site infection (SSI) in colorectal surgery. This study aimed to evaluate the efficacy of subcutaneous suction drains (SSDs) compared with primary skin closure (PC) in class 4 dirty wound surgery. Patients and Methods: Eighty-one patients undergoing open gastrointestinal surgery with class 4 dirty wounds were enrolled in this study, 30 of whom underwent SSD insertion, whereas the other 51 were treated with PC. Because several studies have reported that the median onset of the development of incisional SSI was eight to 13 days after surgery, we used a two-week placement of an SSD. Comparison of patients treated with SSD and PC and multivariable analysis were performed to test the ability of SSD in decreasing the SSI rate. Results: No differences were observed between the two groups in terms of gender, body mass index, American Society of Anesthesiology score, steroid use, presence of diabetes mellitus, peri-operative transfusion, and surgery type. Surgical site infection incidence was lower in the SSD group (6.6%; 2/30) than that in the PC group (23.5%; 12/51; p = 0.069). Multivariable analysis revealed that the presence of diabetes mellitus was an important independent risk factor for incisional SSI, and the placement of an SSD has substantial preventive effects on incisional SSI (p = 0.018 and p = 0.014, respectively). Conclusions: This study suggested the potential importance of a two-week placement of an SSD for preventing incisional SSI in class 4 dirty wound surgery.

Clinical Impact of Two-Week Placement of a Subcutaneous Suction Drain in Preventing Incisional Surgical Site Infection in Open Gastrointestinal Surgery with Class 4 Dirty Wound: A Retrospective Study.

Details of a study on the intramolecular bis-silylation of C-C multiple bonds promoted by a new catalyst system, palladium-tert-alkyl isocyanide, are described. With a disilanyl ether derived from a homoallylic alcohol, intramolecular regioselective addition of the Si-Si linkage to the C=C bond took place to furnish an exo-ring closure product, i.e., 1, 2-oxasilolane. The bis-silylation of alkenes having substituents α to the C=C bond gave trans-3, 4-disubstituted oxasilolanes, while substitution β to the C=C bond favored cis-3, 5-disubstituted oxasilolanes. The 1, 2-oxasilolanes thus produced stereoselectively were oxidatively converted to the corresponding 1, 2, 4-triols. The present methodology for the synthesis of 1, 2, 4-triols was successfully extended to the stereoselective synthesis of 1, 2, 4, 5, 7- and 1, 2, 4, 6, 7-pentaols through a sequence of the intramolecular bis-silylation. The bis-silylation was also performed with alkenes linked to disilanyl groups through a 3-carbon chain and through an amide linkage. Alkenes tethered to disilanyl groups through chains of 2 atoms underwent similar intramolecular bis-silylation. The intramolecular bis-silylation of an alkyne tethered to a disilanyl group furnished a bis-silylated exocyclic olefin. Subsequent hydrogenation from the less-hindered side of the ring produced cis-disubstituted oxasilolane, providing an alternative method for the stereoselective synthesis of 1, 2, 4-triols. The intramolecular bis-silylation under high pressure led to the efficient synthesis of a new cyclic tetrakis(organosilyl)ethene, which possessed a non-twisted structure.

Masahiro Murakami

Papers

New Cycloaddition Reactions of Conjugated Allenes Catalyzed by Transition Metal Complexes

Clinical Impact of Two-Week Placement of a Subcutaneous Suction Drain in Preventing Incisional Surgical Site Infection in Open Gastrointestinal Surgery with Class 4 Dirty Wound: A Retrospective Study.

Intramolecular Bis-silylation Catalyzed by Palladium-Isocyanide

Aromatizing Oligomerization of 1,2-Diisocyanoarene to Quinoxaline Oligomers.