June 2023

Cyclobutenes are highly strained ring systems of considerable synthetic interest that can be accessed via cycloaddition reactions between alkenes and alkynes. However, their traditional preparation relies on photochemical [2+2] cycloadditions that exploit low-wavelength UV radiation emitted from inefficient medium-pressure Hg lamps. This paper reports on the development of a modern approach using a high-power LED set-up emitting at the boundary of UV-A and visible light in conjunction with a continuous-flow reactor. The resulting flow process renders a series of cyclobutenes from maleimides and various commercial alkynes. This provides a more energy-efficient approach that is readily scalable to access multigram quantities of cyclobutenes in high chemical yields and short residence times. The value of these products is exemplified by flow-based hydrogenations yielding highly substituted cyclobutanes which represent sought after building blocks in modern medicinal chemistry programs.

A convenient enantiocontrolled synthesis of allenes (R1R2C=C=CHR3, R1 = aryl/alkyl, R2, R3 = alkyl) is described based on carbenoid eliminative cross-coupling (CEXC) between geometrically pure higher-order α-(methylthio)vinylcuprates, generated in situ by carbocupration of thioalkynes (then activation by addition of n-BuLi), and enantioenriched α-(carbamoyloxy)alkylboronates (15 examples, 30–78% yield, 15–95% ee). The stereochemical fidelity of this CEXC process is substrate dependent, a phenomenon tentatively attributed to a putative organocopper-mediated allene racemization pathway.