A facile synthetic procedure for the production of N-alkylated 3,4-dihydroisoquinolinone derivatives is described. The desired products were obtained by N-alkylation of 3,3 0 -dimethyl-3,4-dihydroisoquinoline derivatives followed by oxidation of the resulting iminium salts. Reaction conditions for both steps were very mild and the desired cyclization products could be obtained in good yield. This strategy allows the generation of N-substituted 3,4-dihydroisoquinolinone derivatives with substituents at the 3-position.

A facile synthetic procedure for 3,4‐dihydronaphthyridinone derivatives is described. This synthetic route involves the cascade reaction of methyl nicotinate having an ethoxyvinyl group with various amines. The desired cyclization products were obtained using pyridylacetaldehyde formation and subsequent reductive amination/cyclization with amines. For the preparation of vinyl ether derivatives, we employed the coupling reaction, and the method would be applicable to various related substrates. Furthermore, all the reactions to N‐alkyl products proceeded rapidly at ambient temperature in good yields using simple and safe protocols. This strategy allows the generation of dihydronaphthyridinone derivatives containing various amines.

Stereoselective synthesis of 4-substituted prolinol derivatives has been developed. Thus, Suzuki-Miyaura cross-coupling of vinyl triflate provided the common synthetic intermediates toward the stereodivergent synthesis of cisand trans-4-substituted prolinols. These two kinds of target compounds were obtained by diastereoselective hydrogenation of the coupling products with Pd/C and Crabtree catalyst, respectively. In addition, the obtained 4-substituted prolinol was transformed to the corresponding proline derivative via oxidation in one step.

Concise synthesis of anticancer active trans-4-(4-octylphenyl)prolinol has been achieved. Regioselective iodination of aromatic compound and subsequent Suzuki-Miyaura cross-coupling with trans-1-octen-1-ylboronic acid produced the desired coupling product. Further transformation of this product afforded trans-4-(4-octylphenyl)prolinol. The synthesis of this anticancer compound has been performed with 23% overall yield and six steps, which have been improved in comparison with those (3.5% overall yield and eight steps) previously reported. The substituted prolinols have been recognized as key and versatile synthetic intermediates for the total synthesis of natural products 1 and other biologically active compounds. 2 In addition, the prolinol is a central structural feature which is found in drug candidates such as anticancer compounds, 3 antivirus compounds, 4 CCR3 receptor antagonists, 5 and sphingosine-1-phosphate agonists. 6 Hanessian's research group found that trans-4-(4-octylphenyl)prolinol (1, Scheme 1) exhibited the anticancer activity against PC3 (IC50 = 9.8 μM) and DU145 (IC50 = 10.6 μM) cell lines in their research of FTY720 analogues which limit nutrient transporter expression but lack sphingosine-1-phosphate activity. 3b,7 The synthetic route of 1, which was reported by Hanessian and co-workers, is depicted in Scheme 1. Protection of trans-4-hydroxy-L-proline (2) with (Boc)2O and subsequent TEMPO oxidation gave ketone 3. The carboxylic acid 3 was treated with t-BuOH/EDC/DMAP to afford ester 4. The ketone