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The Reformatsky reagent derived from ethyl bromoacetate circumvents the challenge associated with the direct regio- and enantioselective iridium-catalyzed allylic alkylation with an unstabilized aliphatic ester enolate. Notably, this work represents the first example of using a Reformatsky reagent in a metal-allyl reaction, which permits the direct construction of enantioenriched β-stereogenic homoallylic esters without preactivation of the pronucleophile or post-reaction modification of the product (e.g., thermal decarboxylation of a 1,3-dicarbonyl). Moreover, the process allows the coupling of a broad range of sterically and electronically diverse electrophiles bearing aryl, heteroaryl and alkenyl derivatives, including the significantly more challenging alkyl-substituted allylic carbonates. The versatility of the ester product is exemplified by a series of functional group manipulations and the development of a concise and efficient enantioselective total synthesis of the natural product, (+)-descurainolide A. Finally, mechanistic studies indicate that the zinc enolate behaves as a soft nucleophile that undergoes outer-sphere alkylation. [ABSTRACT FROM AUTHOR]

Rhodium-catalyzed cyclocarbonylation reactions, which include the Pauson–Khand-type or [2+2+1] reactions, represent a powerful strategy for the synthesis of cyclic ketones through the combination of relatively simple unsaturated groups; namely, alkenes, alkynes, allenes, dienes, heterocumulenes, nitriles, and strained rings with carbon monoxide derived from either CO gas or through the decarbonylation of aldehydes. This chapter examines a variety of methods for the synthesis of carbo- and heterocyclic rings of different sizes, including diastereoselective and enantioselective approaches, and will also present the application of these reactions in the total synthesis of important natural products, as exemplified by (+)-asteriscanolide and (-)-ingenol. [ABSTRACT FROM AUTHOR]

Antibiotics play a significant role in human health because of their ability to treat life-threatening bacterial infections. The growing problems with antibiotic resistance have made the development of new antibiotics a World Health Organization priority. Marinomycin A is a member of a new class of bis-salicylate-containing polyene macrodiolides, which have potent antibiotic activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Herein, we describe a triply convergent synthesis of this agent using the salicylate as a novel molecular switch for the chemoselective construction of the macrodiolide. This strategy raises new questions regarding the biosynthetic role of the salicylate and its potential impact on the mechanism of action of these types of agents. For instance, in contrast to penicillin, which enhances the electrophilicity of the cyclic amide through ring strain, salicylates reduce the electrophilicity of the aryl ester through an intramolecular resonance-assisted hydrogen bond to provide an amide surrogate. [ABSTRACT FROM AUTHOR]