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.

Total synthesis of the tetracyclic diquinane Lycopodium alkaloids magellanine and magellaninone

Diastereoselectivity control in the zirconocene-mediated ring contraction of 4-vinylfuranosides to enantiopure multiply functionalized cyclobutanes.

The stereochemistry of the coupling reactions of oxygen-substituted bromides 8−10 with isobutyraldehyde, benzaldehyde, and cyclohexanecarboxaldehyde in water is described. The examples involving the O-silylated derivatives 8 exhibit moderate anti stereoselectivity. In contrast, rather high (most often in excess of 80:20) syn diastereofacial bias is observed when hydroxy bromides 10 are involved. Consequently, stereocontrolled 1,4-asymmetric induction under aqueous conditions can be realized in either direction on demand. These results are considered to reflect the fact that the siloxy systems enter into C−C bond formation via conventional Felkin−Anh transition state arrangements. The crossover observed for the unprotected analogues is believed to be a consequence of the preferred adoption of chelated transition states, these interactions likely being fundamental to aqueous organometallic chemistry.

Effective 1,4-Asymmetric C−C/C−O Stereoinduction in Indium-Promoted Coupling Reactions of Aldehydes to Protected and Unprotected [1-(Bromomethyl)vinyl] Alkanols. The Status of Intramolecular Chelation within Functionalized Allylindium Reagents

The susceptibility of glycal-derived carbinols to acid-catalyzed ring expansion is described. In the systems prepared from cyclopentanone, Ferrier ionization precedes the pinacol-like Wagner−Meerwein shift, thermodynamic control operates, and high stereoselectivity is seen if a C(6) substituent is present. In contrast, the adducts to cyclobutanone exhibit release of ring strain under kinetically controlled conditions and intercept the oxonium species reversibly formed via direct proton transfer. The results show that the substituents positioned on the glycal ring have a pronounced influence on whether a chair-like or twist-boat transition state geometry is adopted primarily. The composite reaction profiles reveal for the first time the fundamental importance of exothermicity and of substitution in these spiro glycosidation reactions. Since optical activity is preserved in all instances, the utility of this chemistry for the synthesis of bis-C,C-glycosides and more complex oxacyclics appears promising.

Practical Synthesis of Spirocyclic Bis-C,C-glycosides. Mechanistic Models in Explanation of Rearrangement Stereoselectivity and the Bifurcation of Reaction Pathways

Leo A. Paquette

Papers

Total synthesis of the tetracyclic diquinane Lycopodium alkaloids magellanine and magellaninone

Diastereoselectivity control in the zirconocene-mediated ring contraction of 4-vinylfuranosides to enantiopure multiply functionalized cyclobutanes.

Effective 1,4-Asymmetric C−C/C−O Stereoinduction in Indium-Promoted Coupling Reactions of Aldehydes to Protected and Unprotected [1-(Bromomethyl)vinyl] Alkanols. The Status of Intramolecular Chelation within Functionalized Allylindium Reagents

Practical Synthesis of Spirocyclic Bis-C,C-glycosides. Mechanistic Models in Explanation of Rearrangement Stereoselectivity and the Bifurcation of Reaction Pathways

Convergent regiodirected assembly of 2,3-disubstituted furans