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.

Our involvement with the de novo acquisition of taxusin (1) and taxol (2) has been fueled in large part by the enchanting structural features of these molecules and the much heralded antitumor efficacy of 2, particularly in patients beset with refractory ovarian, breast, and lung cancers.1 In combination with the unusual mode of action of 2, which exhibits a remarkable capacity for stabilizing microtubule assembly and deterring cell division,2 the intrinsically exciting promise shown by taxol for benefiting human health has commanded unrivaled attention.

From D-Camphor to the Taxanes: Highly Concise Rearrangement-Based Approaches to Taxusin and Taxol

The cycloalkenones (I) undergo cyclocondensation with ethyl acetoacetate (II) to give the bridged cyclohexenones (III) which are converted to the tricyclic hydroxydienes (VII) as shown in the reaction scheme.

A Convenient Route to 1,3‐Cyclooctatetraenophanes.

Homoallylic alcohols have been prepared from alkenes by direct reaction of the ozonide with an allylic bromide in the presence of zinc.

A Convenient One‐Flask Procedure for the Direct Conversion of Alkenes to Homoallylic Alcohols.

An enantioselective synthesis of both enantiomers of the title ketone 5 from a common achiral β-diketone is reported. Bakers' yeast reduction of 6 cleanly differentiates between the two carbonyl groups to deliver (+)-9 in >90% yield, and with an ee exceeding 98%. Direct xanthate elimination leads to (+)-5. To arrive at the levorotatory antipode, the OH group in the β-hydroxy ketone is transformed into the tetrahydropyranyl ether and the carbonyl group is subsequently reduced in advance of formal dehydration. Oxidation of the deprotected alcohol ultimately reestablishes the carbonyl functionality and delivers (−)-5 of equally high optical purity.

Synthesis of Both Antipodal Forms of 7,7-Dimethylbicyclo(2.2.2)oct-2- en-5-one by Enantiomer Interconversion.

Geometrically and optically pure (3R,5E)- and (3R,5Z)-1,5-heptadien-3-ols undergo anionic oxy-Cope rearrangement under the exclusice control of oxyanion orientation with a 58-64% preference for equatorial oxygen. Six semicyclic dienols have also been synthesized where the preferred oxyanion-driven sigmatropic rearrangement pathway is obligatorily pitted against π-facial biases offered by 4-tert-butylcyclohexenyl, norbornenyl, and camphenyl rings. These rearrangements therefore offer especially stringent tests of those factors that control the level and direction of chirality transfer. The data show the oxyanion to disfavor becoming involved in 1,3-diaxial relationships

Leo A. Paquette

Papers

From D-Camphor to the Taxanes: Highly Concise Rearrangement-Based Approaches to Taxusin and Taxol

A Convenient Route to 1,3‐Cyclooctatetraenophanes.

A Convenient One‐Flask Procedure for the Direct Conversion of Alkenes to Homoallylic Alcohols.

Synthesis of Both Antipodal Forms of 7,7-Dimethylbicyclo(2.2.2)oct-2- en-5-one by Enantiomer Interconversion.

Relevance of Oxyanion Stereochemistry to Chirality Transfer in Anionic Oxy‐Cope Rearrangements.