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 synthesis of dodecahedrane (C20H20) in 1982 generated a great deal of interest in highly symmetric and highly strained hydrocarbons, just as the synthesis of adamantane did more than 20 years ago. Both dodecahedrene and adamantene have proved difficult to synthesize, however, since the rigidly locked skeletons of the saturated systems would enforce a high degree of distortion at the olefinic carbons. A great deal of interest thus centers on the amount of additional energy necessary to incorporate a strained double bond into these systems, relative to an unstrained hydrocarbon. We have successfully measured this \"double-bond strain energy\" by thermochemically bracketing the gas-phase 1,2-eIimination reaction of trifluoroacetoxydodecahedrane. From this thermodynamic measurement, we obtain the relative gas-phase heats of formation of dodecahedrene and dodecahedrane. Attempts to induce the same reaction in trifluoroacetoxyadamantane gave a more ambiguous result, but nevertheless yielded useful thermochemical information. For dodecahedrene, our measurement yields the heat of hydrogenation, which may be compared to that for unstrained systems as a measure of the strain involved in the pyramidalized double bond. Thermodynamic and geometric data from AM1 semiempirical calculations are in good agreement with the experimental results. The present method should be extendable to the thermochemistry of other strained systems. In 1982, Paquette and co-workers reported the first synthesis of dodecahedranel (l), the most complex of the regular \"Platonic solids\". This C20H20 hydrocarbon has generated major interest in a variety of areas, e.g., as an example of an exceptionally symmetric (I,,) and stable system,* as a potential cage for small ions or molecules,3 and as a potential carrier for functional groups of pharmaceutical i n t e r e ~ t . ~ More recently, Paquette et al. have reported the synthesis of a variety of substituted dodecahedraned and have been pursuing the synthesis of dodecahedrene (2): which holds a great deal of interest as a highly strained olefin.' Dodecahedrene should, when eventually examined crystallographically, exhibit a high degree of pyramidalization of the olefinic carbon atoms,* probably with near-tetrahedral geometry a t these

Measurement of the double-bond strain energy in dodecahedrene by thermochemical bracketing of gas-phase ion molecule reactions

(R)-(-)-Isopiperitenone (I) reacts with the chiral, racemic cyclopentenyllithium reagents derived from (II) to give the alcohols (III) and (IV).

Kinetic resolution during condensation of chiral (racemic) cyclopentenyllithiums with (R)-(−)-isopiperitenone. A short route to optically active annulated germacranolides

Treatment of the peristylanedione dioxime (I) with m-chloroperbenzoic acid results in ring closure and oxidation, producing the dinitro compound (II).

Leo A. Paquette

Papers

Measurement of the double-bond strain energy in dodecahedrene by thermochemical bracketing of gas-phase ion molecule reactions

Kinetic resolution during condensation of chiral (racemic) cyclopentenyllithiums with (R)-(−)-isopiperitenone. A short route to optically active annulated germacranolides

Synthesis of nitro derivatives of [4]peristylane having high-density characteristics

The Need for an Incisive Analysis of the Regioselectivity Associated with the Deprotonation of α-Alkoxy and α-Acyloxy Ketones

A convenient route to spirocyclic C-glycosides. Demonstration that ring strain release can override normal operation of the ferrier rearrangement