Scheme 1. Synthesis of α-substituted γ-lactam derivatives of 7. Reagents and conditions: (a) ethyl chloroacetate, KO^tBu, THF, −50 °C to rt, 89%; (b) Cs₂CO₃, alkyl halide, DMF, rt, 52–94%, or for 14e: 1,1,3,3-tetramethylguanidine (20 mol%), acrylonitrile, THF, rt, 55%; (c) Fe(0), FeSO₄ (8 mol%), dioxane : H₂O (4 : 1), reflux; then: methylsulfonyl chloride, NEt₃, 4-(N,N-dimethylamino)pyridine (10 mol%), CH₂Cl₂, rt, 10–30%; (d) LiOH, THF : H₂O : EtOH (2 : 1 : 1), rt, 73–94%; (e) 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU),⁵⁸ⁱPr₂NEt,⁵⁹ MeCN : CH₂Cl₂ (1 : 1), rt, 46–76%; (f) Cs₂CO₃ (2.5 equiv.), alkyl halide (2.2 equiv.), DMF, rt, 9–90%. See Table 2 for structures of 16a–f and 17a–b.