Smyth, MeganMeganSmythMoody, Thomas S.Thomas S.MoodyWharry, ScottScottWharryBaumann, MarcusMarcusBaumann2023-05-102023-05-102023 Thiem2023-05-04Accounts and Rapid Communications in Chemical Synthesis (Synlett)0936-5214http://hdl.handle.net/10197/24414Cyclobutenes 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.enPhotochemistryCycloadditionCyclobuteneLight emitting diode (LED)Flow chemistryJournal Article243528529010.1055/a-2086-06302023-05-0819/IFA/742020/FFP-P/8712https://creativecommons.org/licenses/by/3.0/ie/