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.

Endoperoxidation of conformationally fixed norcaradienes by singlet oxygen. Frontier molecular orbital basis for the operability of 1O2 quenching by hydrazides

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.

Stereoselective Construction of the Dicyclopenta(a,d)cyclooctene Core of the Ceroplastin Sesterterpenes by Way of the Anionic Oxy‐Cope Rearrangement.

A program directed toward a total synthesis of polycavernoside A is described The synthesis of five building blocks is detailed The first of two electrophilic units, the lactone 3, was prepared in four steps from the known enantiomerically pure oxirane 15 Pyranyl aldehyde 5 was elaborated in turn from l-malic acid via 10 While the route to 30 involved 3 as a starting material, dithiane 2 was obtained in a straightforward manner from 10 as well The merging of the chiral sectors could not be accomplished by way of the lithiated dithianyl anions, presumably as a consequence of their heightened basicity The strategic incorporation of the trienyl sector was accomplished, although no attempt was made to control the diastereoselectivity of the process

A Modular Enantioselective Approach to Construction of the Macrolactone Core of Polycavernoside A.

A practical application of the photooxygenation chemistry of 3-substituted furans to construction of the zaragozic acid/squalestatin backbone is described. Although addition of 3-lithiofuran to the tartrate-derived aldehyde 7 proceeds without chelation control to give a 1:1 mixture of diastereomeric alcohols 8, it is demonstrated initially that ready conversion to the polyfunctional intermediate 10 is possible by sequential treatment of 9 with singlet oxygen, sodium borohydride, and triisopropylsilyl triflate. The actual enantiocontrolled route consisted of oxidation of 8 to the ketone and Wittig olefination of the latter in advance of asymmetric dihydroxylation with AD-mix-beta. Once this series of transformations had been accomplished, formation of the target product 30 was realized by an entirely comparable photooxygenation.

Evaluation of Furan Photooxygenation as a Device for Construction of the Zaragozic Acid (Squalestatin) Core.

The oxygenated ABC network of the potent insect antifeedant dumsin has been expediently assembled in a totally stereocontrolled manner by exploiting the acylation of a lactone carbonyl with a masked keto anion equivalent.

Leo A. Paquette

Papers

Endoperoxidation of conformationally fixed norcaradienes by singlet oxygen. Frontier molecular orbital basis for the operability of 1O2 quenching by hydrazides

Stereoselective Construction of the Dicyclopenta(a,d)cyclooctene Core of the Ceroplastin Sesterterpenes by Way of the Anionic Oxy‐Cope Rearrangement.

A Modular Enantioselective Approach to Construction of the Macrolactone Core of Polycavernoside A.

Evaluation of Furan Photooxygenation as a Device for Construction of the Zaragozic Acid (Squalestatin) Core.

Efficient Stereocontrolled Synthesis of the ABC Subunit of Dumsin.