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

Marine natural products.

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

4.2.8. Reductive Coupling 3109 5. Reaction of Aromatic Compounds 3110 5.1. Electrophilic Substitutions 3110 5.2. Radical Substitution 3111 5.3. Oxidative Coupling 3111 5.4. Photochemical Reactions 3111 6. Reaction of Carbonyl Compounds 3111 6.1. Nucleophilic Additions 3111 6.1.1. Allylation 3111 6.1.2. Propargylation 3120 6.1.3. Benzylation 3121 6.1.4. Arylation/Vinylation 3121 6.1.5. Alkynylation 3121 6.1.6. Alkylation 3121 6.1.7. Reformatsky-Type Reaction 3122 6.1.8. Direct Aldol Reaction 3122 6.1.9. Mukaiyama Aldol Reaction 3124 6.1.10. Hydrogen Cyanide Addition 3125 6.2. Pinacol Coupling 3126 6.3. Wittig Reactions 3126 7. Reaction of R,â-Unsaturated Carbonyl Compounds 3127

Organic Reactions in Aqueous Media with a Focus on Carbon−Carbon Bond Formations: A Decade Update

The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Cascade reactions in total synthesis.

The ready availability of 4-t-butyldimethylsiloxy-perhydro-12a,13,13-trimethyl-6,10-methanobenzocyclodecene-7,12-dione(5) has prompted examination of a convenient means for carbonyl transposition in its A-ring. Attempts to implement such chemistry directly on 5 and its silyl-protected derivative suffer from a kinetic proclivity for transannular capture of the enolate anion. This undesirable process was circumvented by reduction of the C9 carbonyl following conversion to a silyl enol ether 8. Once the resulting 9a-alcohol was protected as its MOM ether, the enolates of 10a and 10b could be efficiently oxygenated at C13 by treatment with the Davis sulfonyl oxaziridine despite severe steric congestion in that locale. The resultant α-alcohol 11a could be epimerized to the 13β-isomer by exposure to potassium hexamethyldisilazide

A-Ring Oxygenation Studies in Bridgehead Hydroxyl-Substituted trans- Tricyclo(9.3.1.03,8)pentadecan-14-one Congeners of Taxol.

Synthesis of meso‐ and dl‐2,2′‐Methylenebis[tetrahydro‐2‐furanmethanol]. Potential Building Blocks for the Construction of Ionophores Housing Spirotetrahydrofuranyl Motifs.

Suitability of the Claisen Ring Expansion Protocol for Crenulide Diterpene Construction.

Addition of methyl (E)-4-bromo-3-methoxycrotonate to aldehydes in the presence of indium and water delivers β-hydroxy esters, acidic hydrolysis of which leads to Knoevenagel-like adducts

An Indium‐Promoted Alternative to the Knoevenagel Condensation of Aldehydes with Methyl Acetoacetate.

A program directed toward a general synthesis of α-methylenelactones cis- or trans-fused to larger rings is reported. The protocol originates with two ω-unsaturated aldehydes of the same or different chain length. One of these is initially transformed by way of the Baylis–Hillman reaction into a functionalized allylic bromide. Merger of the two building blocks is subsequently accomplished in aqueous solution with powdered indium metal serving as the initiator. Once the lactone ring is crafted, the end products are generated by application of ring-closing metathesis. The central issues surrounding this final step are the effects of the stereochemical disposition of the side chains, the consequences of ring strain, and the locus of the double bonds on cyclization efficiency.

Leo A. Paquette

Papers

A-Ring Oxygenation Studies in Bridgehead Hydroxyl-Substituted trans- Tricyclo(9.3.1.03,8)pentadecan-14-one Congeners of Taxol.

Synthesis of meso‐ and dl‐2,2′‐Methylenebis[tetrahydro‐2‐furanmethanol]. Potential Building Blocks for the Construction of Ionophores Housing Spirotetrahydrofuranyl Motifs.

Suitability of the Claisen Ring Expansion Protocol for Crenulide Diterpene Construction.

An Indium‐Promoted Alternative to the Knoevenagel Condensation of Aldehydes with Methyl Acetoacetate.

Tandem Development of Aqueous Indium Chemistry and Ring-Closing Metathesis as a General Route to Fused-Ring α-Methylene-γ-butyrolactones.