Dines (21) are reacted with those of esters or ketones (22), variations in redox potentials are sufficiently massive, and heterodimerization products like 23a-c are formed exclusively. This order (+)-Citronellal REACTION furnishes 1,4-dicarbonyl solutions (23) with the concomitant creation of two vicinal stereocenters inside a redox-economical style.70 Such motifs may be located in a variety of natural products and pharmaceuticals. The heterocoupling reaction hence permitted quick syntheses of a metalloproteinase inhibitor (24)69b plus the all-natural solution bursehernin (25);69 the intramolecular variant was harnessed to forge very congested C-C bonds in our syntheses of (+)-stephacidin A (26) and (+)-avrainvillamide (27), as well as (-)-stephacidin B (28) (Figure 2E).68 Moreover, oxidative enolate heterocoupling has found use in each industrial and academic circles. For example, Gavai and coworkers from Bristol-Myers Squibb applied this strategy to synthesize a series of anticancer agents like BMS-906024 (29) (at the moment in phase II clinical trials).71 The groups of Overman,72a,b Tang,72c Nicolaou,72d Yang,72e and Thomson72f,g have applied this strategy towards the syntheses of (-)-actinophyllic acid (30), spirobacillene A (31), furanocembranoid precursors which include 32, (+)-propindilactone G (33), and metacycloprodigiosin (34), and propolisbenzofuran B (35), respectively.PerspectiveDEVELOPMENT Of the BORONO-MINISCI REACTION Our interest in silver-mediated radical reactions originated from the total syntheses from the axinellamines (38),73 massidine,74 and palau’amine (Figure three).75 These highly complicated pyrrole- imidazole alkaloids each and every possess a dense array of nitrogenous functionalities, among which the typical guanidinium hemiaminal motif stands out as a vexing function. To avert concessional maneuvers, the installation of this sensitive moiety was deferred to a late stage via a direct oxidation of C-20. This method would simultaneously allow for the synthesis on the complete alkaloid family members from a popular intermediate. After extensive experimentation, silver(II) picolinate was identified as the optimal oxidant for this unique transformation (36 37) (Figure 3A). Strikingly, the C-20 position was oxidized with admirable chemo- and regioselectivity, delivering the hemiaminal without having over-oxidation. (The product is conceivably less difficult to oxidize than the starting material!) This enabling reaction not just led towards the total syntheses of your axinellamines, massidine, and palau’amine but also allowed us to procure axinellamines in gram quantities to establish their broadspectrum anti-bacterial activities.73d Though silver(II) picolinate (CAS Registry No. 14783-00-7) has now been commercialized by Sigma-Aldrich, the initial scope of this reaction is at present limited for the esoteric region of guanidine oxidation.76 We had been thus motivated to look into other silvercatalyzed processes with additional translational prospective. The venerable Minisci reaction is a single such example wherein a carboxylic acid undergoes radical decarboxylation in the presence of a silver catalyst.77 The alkyl radical thus formed can directly functionalize electron-deficient heteroarenes (39). The PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21382948 importance of those omnipresent heteroarenes cannot be overstatedthey are vital to life and are identified in vitamins, drugs, dyes, pesticides, and polymers.78 Despite the tremendous amount of function describing their functionalizations, societal needs call for more-efficient syntheses of (hetero)biaryl frameworks to access various p.