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Azido nucleosides couple with phosphoramidites via an initial iminophosphorane, which eliminates acrylonitrile to generate the coupled dimer P(V) product. The vulnerable phosphite triester intermediate is bypassed entirely, making the methodology very suitable to solution-phase synthesis. This new coupling protocol requires no protection of the 5'-OH function and provides a new method of installing internucleosidic phosphorodiamidate bonds with near quantitative yields.

Understanding the nature of the intermediate species operating within a palladium catalytic cycle is crucial for developing efficient cross-coupling reactions. Even though the XPhos/Pd(OAc) 2 catalytic system has found numerous applications, the nature of the active catalytic species remains elusive. A Pd 0 complex ligated to XPhos has been detected and characterized in situ for the first time using cyclic voltammetry and NMR techniques. In the presence of XPhos, Pd(OAc) 2 initially associates with the ligand to form a complex in solution, which has been characterized as Pd II (OAc) 2 (XPhos). This Pd II center is then reduced to the Pd 0 (XPhos) 2 species by an intramolecular process. This study also sheds light on the formation of Pd I -Pd I dimers. Finally, a kinetic study probes a dissociative mechanism for the oxidative addition with aryl halides involving Pd 0 (XPhos) as the reactive species in equilibrium with the unreactive Pd 0 (XPhos) 2 . Remarkably, the reportedly poorly reactive PhCl reacts at room temperature in the oxidative addition, which confirms the crucial role of the XPhos ligand in the activation of aryl chlorides., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aryl imidazolylsulfonates participate as electrophilic coupling partners in palladium-mediated cross-coupling reactions. The aryl imidazolylsulfonates display good stability while maintaining good reactivity in a variety of palladium-catalyzed coupling reactions. Imidazolylsulfonates are a practical and economic alternative to triflates.

In this paper, we disclose an efficient one-pot procedure for the preparation of substituted 1,8-naphthyridin-4-one analogues. Previous efforts to effect this type of transformation were complicated by the formation of benzene tricarboxylate. Via the use of excess base, the impurity formation was completely inhibited. This allowed for the clean preparation of the desired intermediate and subsequent formation of naphthyridone analogues in a single flask, which could then be crystallized directly from the reaction mixture in good yield and high purity.

The total syntheses of the potent protein kinase C inhibitors calphostins A, B, C, and D as well as a variety of structural analogues are reported. An aminobenzannulation reaction of an enantiopure chromium Fischer carbene complex is utilized to prepare a pentasubstituted naphthylamine. After optimization of side-chain substituents, conversion of the naphthylamine to an o-naphthoquinone was followed by biomimetic oxidative dimerization using trifluoroacetic acid and air yielding a 1:2 P/M mixture of atropisomeric perylenequinones. Thermal equilibration to a 3:1 P:M atropisomeric ratio and separation of the perylenequinones followed by side chain desymmetrization and functionalization led to the total synthesis of enantio- and diastereomerically pure calphostin C in only twelve steps from commercially available starting materials. In addition, calphostins A, B, D, and several structural analogues were prepared to evaluate biological activities.