Synthesis of highly polarized [3]dendralenes and their Diels–Alder reactions

Abstract

The diene-transmissive Diels–Alder (DTDA) reactions of dendralenes are emerging as a powerful synthetic tool. To date, these processes have been studied with non-polarized or mildly polarized species. We now present an expedient synthesis of strongly electron-deficient [3]dendralenes and demonstrate, for the first time, their DTDA reactions with electron-poor dienophiles. While the combination of two electron-poor partners is believed to be generally disfavored, DTDA reactions reported herein proceed at 100 °C with high yields and stereoselectivities. DFT calculations show that this electronically disfavored process is encouraged by a steric effect of the vinylic moiety within the dendralene core, driving the diene segment into the s-cis conformation, thereby lowering the activation energy by 2–3 kcal mol⁻¹. While the free energy barrier is typically lower for the second cycloaddition, the two barriers become similar for dendralenes with a cyclic enone fragment, which allows a controlled stepwise addition of two different dienophiles.