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 concept of spirocyclic restriction, when generically applied to nucleoside mimics, allows for the preparation of diastereomeric pairs carrying either a syn- or anti-oriented hydroxyl at C-5'. Reported herein are convenient synthetic routes to enantiomerically pure 1-oxaspiro[4.4]nonanes featuring fully dihydroxylated end products as well as congeners having dideoxy and didehydrodideoxy substitution patterns. Notable use is made of the capacity for introducing unsaturation in the furanose sector via phenylsulfenylation and the incorporation of uracil and thymine by way of their silylated derivatives under catalysis with stannic chloride.

Conformational restriction of nucleosides by spirocyclic annulation at C4' including synthesis of the complementary dideoxy and didehydrodideoxy analogues.

Through-bond interaction via cyclobutane relay orbitals as a means of extending conjugation. Synthesis of tricyclo[5.5.0.02,8]dodecatetraene, tricyclo[5.3.0.02,8]deca-3,5,9-triene, and 9,10-dimethylenetricyclo[5.3.0.02,8]deca-3,5-diene

Stereocontrolled total synthesis of (.+-.)-pentalenolactone P methyl ester

Die Photoelektronenspektren von Dihydrotriquinacen (3) und 2a,4a,8a,8b-Tetrahydrocyclopent-[cd]azulen (4) wurden untersucht. Das Wechselwirkungsintegral, das die Homokonjugation zwischen den isolierten Doppelbindungen in 3 und 4 beschreibt, betragt β′ > −0.35 eV. Das Wechselwirkungsintegral zwischen dem a “-Orbital des Butadienteils und der a”-Kombination der isolierten Doppelbindungen in 4 last sich mit Hilfe der Photoelektronenspektroskopie nicht bestimmen.



On the Homoconjugation in Triquinacene and 2a,4a,8a,8b-Tetrahydrocyclopent[cd]azulene. Photoelectronspectroscopic Investigations



The photoelectron spectra of dihydrotriquinacene (3) and 2a,4a,8a,8b-tetrahydrocyclopent[cd]-azulene (4) have been investigated. The resonance integral which is a measure for the homoconjugation between the isolated double bonds in 3 and 4 was found to be β′ > −0.35 eV. The interaction integral between the a “ orbital of the butadiene moiety and the a” linear combination of the isolated double bonds in 4 can not be determined by means of photoelectron spectroscopy.

Zur Frage der Homokonjugation in Triquinacen und 2a,4a,8a,8b‐Tetrahydrocyclopent [cd]azulen. Photoelektronenspektroskopische Untersuchungen

Bicyclo[3.2.1]octanediones such as 9, which are readily available by double carbonylation of (1,3-cyclohexadiene)iron tricarbonyl complexes according to Eilbracht, are amenable to regiospecific methylenation under Wittig conditions. Reduction of 10 with copper hydride leads to 11, which can be resolved by application of Johnson's sulfoximine technology and oxidized to give the enantiopure antipodes of 10. Variously substituted cyclopentenyl anions undergo 1,2-addition to 10, providing carbinols which are capable of anionic oxy-Cope rearrangement via chair transition states. These structural reorganizations are fully stereocontrolled and lead directly to functionalized dicyclopenta[a,d]cyclooctenes. When 11 is treated analogously, only [1,3] sigmatropy is observed and inversion of stereochemistry at the migrating carbon prevails. Both processes exhibit impressive scaffolding powers and are characterized by brevity.

Leo A. Paquette

Papers

Conformational restriction of nucleosides by spirocyclic annulation at C4' including synthesis of the complementary dideoxy and didehydrodideoxy analogues.

Through-bond interaction via cyclobutane relay orbitals as a means of extending conjugation. Synthesis of tricyclo[5.5.0.02,8]dodecatetraene, tricyclo[5.3.0.02,8]deca-3,5,9-triene, and 9,10-dimethylenetricyclo[5.3.0.02,8]deca-3,5-diene

Stereocontrolled total synthesis of (.+-.)-pentalenolactone P methyl ester

Zur Frage der Homokonjugation in Triquinacen und 2a,4a,8a,8b‐Tetrahydrocyclopent [cd]azulen. Photoelektronenspektroskopische Untersuchungen

Stereoselective Construction of the Dicyclopenta[a,d]cyclooctene Core of the Ceroplastin Sesterterpenes by Way of the Anionic Oxy-Cope Rearrangement