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 feasibility of the title reaction has been pursued for the purpose of advancing a concise total synthesis of Taxol. Of the two closely related series examined, the first featured an exo-methylene group at C4. The second consisted of an α-epoxide at that site. Strikingly, the olefinic construct proved inert to attempted α-ketol rearrangement. In contrast, the oxiranyl derivative isomerized smoothly. The reaction sequence associated with arrival at taxane 18 is short (15 steps from a d-camphor derivative) and notably efficient. The thermodynamic issues that are raised by this investigation have been clarified by an assessment of molecular mechanics-derived (MM3) steric energy calculations.

A Delicate Balance of Energetics. Subtleties Associated with α-Ketol-Based Bridge Migration To Afford 9-Keto-10β-p-methoxybenzyloxytaxanes

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

Gas-phase basicities of cubane, dodecahedrane, and methyl- and 1,16-dimethyldodecahedrane as measured by Fourier transform ion cyclotron resonance mass spectrometry

Highly diastereocontrolled synthesis of the C1–C25 domain of sanglifehrin A

Addition der Verbindungen (II) an das Propella-tetraen (I) gibt die Produkte (III), aus denen die Derivate (IV) bzw. (V) erhalten werden.

Leo A. Paquette

Papers

A Delicate Balance of Energetics. Subtleties Associated with α-Ketol-Based Bridge Migration To Afford 9-Keto-10β-p-methoxybenzyloxytaxanes

Synthesis of Both Antipodal Forms of 7,7-Dimethylbicyclo[2.2.2]oct-2-en-5-one by Enantiomer Interconversion

Gas-phase basicities of cubane, dodecahedrane, and methyl- and 1,16-dimethyldodecahedrane as measured by Fourier transform ion cyclotron resonance mass spectrometry

Highly diastereocontrolled synthesis of the C1–C25 domain of sanglifehrin A

Stereoreversed electrophilic additions to 3-norcarenes. Insight into the relative steric demands of singlet oxygen in the ene reaction