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.

Total Synthesis of the Tetracyclic Diquinane Lycopodium Alkaloids Magellanine and Magellaninone.

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

The enantiopure disulfonamides 7a−c have been prepared from the C2-symmetric diketone 2, a starting material conveniently accessible from the “dimerization” of (+)-verbenone. These ligands, when treated with titanium isopropoxide and diethylzinc, function as catalysts for the enantioselective alkylation of aldehydes. Stereoselectivity levels ranging from 72 to 98% ee are seen depending on the structural characteristics of the aldehyde. In all cases, the absolute configuration of the carbinol product is R. A working mechanistic model is advanced for the purpose of rationalizing the high levels and direction of asymmetric induction exhibited by these VERDI catalysts.

Synthesis of Enantiopure C2-Symmetric VERDI Disulfonamides and Their Application to the Catalytic Enantioselective Addition of Diethylzinc to Aromatic and Aliphatic Aldehydes.

Decahydro-1,6:3,4-dimethano-3a-nitrocyclobuta [1,2:3,4]dicyclopentene-2,5-dione (II), C12-H11NO4, Mr = 233.2, monoclinic, P2(1)/n, a = 13.378 (7), b = 6.614 (1), c = 23.040 (15) A, beta = 92.53 (5) degrees, V = 2036.6 (4) A3, Z = 8, D chi = 1.521 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 9.3 cm-1, F(000) = 1312, T = 293 K, final R = 0.047, wR = 0.075 for 3075 reflections with I greater than 3 sigma(I). There are no unusually short intermolecular distances. A comparison of the molecular densities and packing coefficients of (I) [4]peristylane-1,5-dione with (II), indicates that the change in crystal density from (I) (1.415 g cm-3) to (II) (1.521 g cm-3) is the sole result of an increase in molecular density with NO2 substitution. The packing coefficients for (I) and (II) are identical.

Leo A. Paquette

Papers

Total Synthesis of the Tetracyclic Diquinane Lycopodium Alkaloids Magellanine and Magellaninone.

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

Synthesis of Enantiopure C2-Symmetric VERDI Disulfonamides and Their Application to the Catalytic Enantioselective Addition of Diethylzinc to Aromatic and Aliphatic Aldehydes.

Structure of 9-nitro-[4]peristylane-1,5-dione.

Preparatively Useful Dehydrogenative Method for Dodecahedrane Synthesis.