Completion of the Set: Synthesis of the (6,X')-Flubromazepam Positional Isomers as Standards for Forensic Analysis.

Mounting concern among forensic examiners regarding the emergence of positional isomers as technically legal alternatives to scheduled benzodiazepines has encouraged the preemptive synthesis of analogues as standards. Recently, flubromazepam was identified by the Drug Enforcement Administration for future scheduling, and subsequently, 9 of the 12 possible flubromazepam isomers were synthesized. However, the three (6,X')-isomers proved inaccessible via that approach. Herein, through a redesigned synthetic approach, the remaining three isomers were obtained, thus completing the set and enabling future forensic analysis.

Calcium-Catalyzed Formal [5 + 2] Cycloadditions of Alkylidene ß-Ketoesters with Olefins: Chemodivergent Synthesis of Highly Functionalized Cyclohepta[b]indole Derivatives.

The calcium-catalyzed, formal [5 + 2] cycloaddition of indolyl alkylidene ß-ketoesters with mono- and disubstituted aryl olefins to form cyclohepta[b]indole derivatives has been established. Unanticipated chemodivergence with phenyl vinyl sulfide/ether revealed a double [5 + 2] cycloaddition cascade providing ethano-bridged cyclohepta[b]indoles. Overall, the method's highlights include: (1) use of a green, calcium-based catalyst (2.5 mol % loading); (2) reaction times under 1 h; (3) mild reaction conditions; (4) substrate-derived chemodivergence; (5) functional group tolerance; and (6) examples of derivatization.