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 levels of diastereoselection attainable during condensation of the bicyclo[2.2.2]octenones 5-7 with organometallics derived from a selec- tion of the vinyl bromides 8-12 have been determined. The 1,2-additions involving 6 exhibit ercellent molecular recognition (>98:2) during syn (endo) addition to the carbonyl group. The diastereoselectivities asso- ciated with the capture of 5 and 7 are lower and more variable, although still respectable in several examples. In all cases, the dominant pro- duct is the alcohol in which the C-5 substituent on the nucleophilic submit is β-oriented

Diastereoselectivities Associated with the 1,2-Addition of Chiral ( Racemic) Cyclopentenyl Organometallics to Bicyclo(2.2.2)octenones.

A practical route for the total synthesis of 8,9-secokaurene diterpenes is described. The central step is the [3.3]sigmatropic rearrangement of spirocyclic intermediates such as 35, 40, and 41. All three compounds must necessarily respond identically to properly install the absolute configuration of the bridgehead methine carbon. The total synthesis of (−)-O-methylshikoccin (2b) was realized in 8% overall yield from the Wieland−Miescher ketone 9. Its naturally occurring epoxide 47 was prepared with comparable efficiency. The preparative route developed herein should provide a general entry into this important class of diterpenoids.

First Synthesis of Cytotoxic 8,9-Secokaurene Diterpenoids. An Enantioselective Route to (-)-O-Methylshikoccin and (+)-O-Methylepoxyshikoccin.

Cyclization to Stereoisomeric Hexahydro‐3,6‐pentaleno(1,6‐cd)pyran‐1( 3H)‐ones. A Model Study Explains the Preference for trans Products.

A Ring-Expansion Route to Analogues of Dideoxyhydantocidin.

Full Control of Regioselectivity in Linear and Angular Polyquinane Construction from Squarate Esters by Incorporation of a Leaving Group into a Single Vinyl Anion Reactant.

Leo A. Paquette

Papers

Diastereoselectivities Associated with the 1,2-Addition of Chiral ( Racemic) Cyclopentenyl Organometallics to Bicyclo(2.2.2)octenones.

First Synthesis of Cytotoxic 8,9-Secokaurene Diterpenoids. An Enantioselective Route to (-)-O-Methylshikoccin and (+)-O-Methylepoxyshikoccin.

Cyclization to Stereoisomeric Hexahydro‐3,6‐pentaleno(1,6‐cd)pyran‐1( 3H)‐ones. A Model Study Explains the Preference for trans Products.

A Ring-Expansion Route to Analogues of Dideoxyhydantocidin.

Full Control of Regioselectivity in Linear and Angular Polyquinane Construction from Squarate Esters by Incorporation of a Leaving Group into a Single Vinyl Anion Reactant.