An enantioselective aza-Wacker-type reaction was developed. When alkenyl sulfonamide substrates were treated with the Pd-SPRIX catalyst in the presence of oxone as an oxidant, the olefin was attacked intramolecularly by the nitrogen nucleophile to construct several heterocycles such as morpholines, piperazines, piperidines, and their benzo-fused derivatives in up to 88% yield with up to 80% ee.A six-membered nitrogen-containing heterocycle, such as morpholine, piperazine, and piperidine, has been recognized as an important substructure in synthetic chemistry. 1 In particular, N-heterocycles with a chiral center at the α-position of the nitrogen atom are broadly found in natural products and biologically active compounds, e.g. flumequine, 2 indivavir, 3 angustureine, 4a,b galipinine, 4c,d and aprepitant 5 (Figure 1). Hence, various protocols have been developed for the construction of optically active sixmembered N-heterocyclic skeletons. 6 Enantioselective Pdcatalyzed C−N bond-forming oxidative cyclization, so-called aza-Wacker-type cyclization, is expected to be a highly useful and straightforward method. 7 However, despite many precedents of five-membered ring formation, 8 the aza-Wacker-type cyclization leading to six-membered nitrogen heterocycles has scarcely been reported. 9,10 In 2012, Stahl and Lu published aza-Wacker-type cyclization of alkenyl sulfonamide substrates

A stable, reusable, and insoluble poly­(4-vinylpyridine) nickel catalyst (P4VP-NiCl2) was prepared through the molecular convolution of poly­(4-vinylpyridine) (P4VP) and nickel chloride. We proposed a coordination structure of the Ni center in the precatalyst based on elemental analysis and Ni K-edge XANES, and we confirmed that it is consistent with Ni K-edge EXAFS. The Suzuki–Miyaura-type coupling of aryl halides and arylboronic esters proceeded using P4VP-NiCl2 (0.1 mol % Ni) to give the corresponding biaryl compounds in up to 94% yield. Surprisingly, when the same reaction of aryl halides and arylboronic acid/ester was carried out in the presence of amides, the amidation proceeded predominantly to give the corresponding arylamides in up to 99% yield. In contrast, the reaction of aryl halides and amides in the absence of arylboronic acid/ester did not proceed. P4VP-NiCl2 successfully catalyzed the lactamization for preparing phenanthridinone. P4VP-NiCl2 was reused five times without significant loss of catalytic activity. Pharmaceuticals, natural products, and biologically active compounds were synthesized efficiently using P4VP-NiCl2 catalysis. Nickel contamination in the prepared pharmaceutical compounds was not detected by ICP-MS analysis. The reaction was scaled to multigrams without any loss of chemical yield. Mechanistic studies for both Suzuki–Miyaura and amidation were performed.

Herein, we report the development of aryl halide-dependent chemoselective reactions, viz., the Buchwald–Hartwig type coupling reaction of an aryl iodide with an arylboronic acid and an aryl amine in the presence of a heterogeneous and reusable nickel catalyst and the Suzuki–Miyaura type coupling of an aryl chloride under similar conditions. Control experiments revealed that the presence of stoichiometric amounts of the phenylboronic acid/ester and aryl amine are essential for both reactions. NMR and XAFS studies suggested the formation of a boron-amine “ate” complex.

A convoluted poly­(4-vinylpyridine) cobalt­(II) (P4VP-CoCl2) system was developed as a stable and reusable heterogeneous catalyst. The local structure near the Co atom was determined on the basis of experimental data and theoretical calculations. This immobilized cobalt catalyst showed high selectivity and catalytic activity in the [2 + 2 + 2] cyclotrimerization of terminal aryl alkynes. With 0.033 mol % P4VP-CoCl2, the regioselective formation of 1,3,5-triarylbenzene was realized without 1,2,4-triarylbenzene formation. Further, a multigram-scale (11 g) reaction proceeded efficiently. In addition, the polymer-supported catalyst was successfully recovered and used three times. X-ray photoelectron spectroscopy analysis of the recovered catalyst suggested that cobalt was in the +2 oxidation state. The 1,3,5-triarylbenzene derivatives were applied to the synthesis of a molecular beam electron resist and a polycyclic aromatic hydrocarbon.

To improve product yields in synthetic reactions, it is important to use appropriate catalysts. In this study, we used machine learning to design catalysts for a reaction system in which both Buchwald−Hartwig-type and Suzuki−Miyaura-type cross-coupling reactions proceed simultaneously. First, using an existing dataset, yield prediction models were constructed with machine learning between experimental conditions, including the substrate and catalyst and the yields of the two products. Seven methods for calculating both the substrate and catalyst descriptors were proposed, and the predictive ability of the yield prediction models was discussed in terms of the descriptors and machine learning methods. Then, the constructed models were used to predict the compound yields for new combinations of substrates and catalysts, and the predictions were experimentally validated with high reproducibility, confirming that machine learning can predict yields from experimental conditions with high accuracy. In addition, to design catalysts that will improve the yields in our dataset, we added datasets collected from scientific papers and designed catalyst ligands. The proposed catalyst candidates were tested in actual synthetic experiments, and the experimental results exceeded the existing yields.