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.

Several optically pure cis-tricyclo[9.3.1.0 3,8 ]pentadecanones have been prepared via anionic oxy-Cope rearrangement of exo-norbornanol precursors that have been obtained by convergent coupling of two functionalized reaction partners. The sigmatropic rearrangement is shown to proceed with exceptionally good stereochemical transmission because of universal adherence to the same endochair transition state. The atropisomeric aspects of this pivotal transformation are addressed. Also investigated was the proclivity of the products to undergo transannular hemiketal formation following osmylation of the bridgehead double bond. As matters turn out, the operation or nonoperation of this intramolecular addition to the C-9 carbonyl group is amenable to control merely by adjusting properly the stereochemistry of a single pendant substituent

A Means for Stereocontrolled Introduction of the C‐2 Oxygen Substituent in Functionalized cis‐Tricyclo(9.3.1.03,8)pentadecanones Related to Taxol.

Electronic control of stereoselectivity. 9. the stereochemical course of electrophilic additions to aryl-substituted benzobicyclo(2.2.2)octadienes

Fully enantio-controlled routes to two major segments of the newly discovered immunosuppressants sanglifehrin A and C are described.

Synthesis of the Tripeptide (C1—N12) and Hydroxylated Hexadecene (C26—C41) Domains of Sanglifehrin A and C.

Indium-promoted additions of (Z)-2-(bromomethyl)-2-butenoate to several α-(tert-butyldimethylsiloxy) and α-(benzyloxy) aldehydes in water have been examined in order to assess the direction and sense of asymmetric induction in these coupling reactions. High levels of the 3,4-syn;4,5-anti diastereomers were produced, reflecting the promising synthetic potential of this chemistry. This stereodifferentiation has been attributed to the strong geometric bias exercised by this allylindium reagent and adherence to a Felkin−Ahn transition-state alignment. Support for this interpretation was gained by comparing the fate of (E)-cinnamyl bromide under comparable circumstances. In this case, the 3,4-anti;4,5-anti diastereomer predominated as expected.

Experimental Test of Setting Three Contiguous Stereogenic Centers in Water. Diastereoselective Coupling of Geometrically Biased Allylic Bromides to α-Oxy Aldehydes with Indium.

Two groups of tetrahydrofuranyl-substituted long-chain carboxylic acids have been prepared under total stereochemical control. The diastereomeric ionophores were subsequently evaluated for their capability of binding alkali metal ions computationally by Amber force field calculations, experimentally by means of the picrate extraction method, and by mediating the transport of Li+ and Na+ through phospholipid bilayers.

Leo A. Paquette

Papers

A Means for Stereocontrolled Introduction of the C‐2 Oxygen Substituent in Functionalized cis‐Tricyclo(9.3.1.03,8)pentadecanones Related to Taxol.

Electronic control of stereoselectivity. 9. the stereochemical course of electrophilic additions to aryl-substituted benzobicyclo(2.2.2)octadienes

Synthesis of the Tripeptide (C1—N12) and Hydroxylated Hexadecene (C26—C41) Domains of Sanglifehrin A and C.

Experimental Test of Setting Three Contiguous Stereogenic Centers in Water. Diastereoselective Coupling of Geometrically Biased Allylic Bromides to α-Oxy Aldehydes with Indium.

Vicinal Tetrahydrofuran Polysubstitution of Simulated Fatty Acids.