Nitrogen hetereocycles are the most important class of compounds in both pharmaceutical and agrochemical industries. Particularly, tetrahydroquinoline(THQ) ring system is one of the most commonly found structural motif in a wide variety of biologically active natural products and pharmaceutical relevant therapeutic agents. Therefore, it is not surprising that intensive synthetic efforts have been devoted to the construction of these frameworks over the past few decades. Herein, we describe a formal [4+2] cycloaddition reaction between ethynyl benzoxazinanone and silyloxyfuran catalysed by a chiral copper-Pybox complex. The base additive of N-methyl morpholine was found to be beneficial to both the yield and stereoselectivity of the reaction. A series of THQs bearing three continuous chiral centers and one terminal alkyne function were obtained in high yields with excellent drs and ee's in most cases. The utility of this methodology was demonstrated by 1 mmol scale synthesis, removal of the the protecting group on the nitrogen of cyclized products, and derivetizations of the terminal alkyne functionality of cyclized products. Further work is currently underway to better understand the specific role of tertiary amine additive in this copper-based catalysis system.

Asymmetric catalyzed cycloaddition via copper-allenylidene process for preparation of tetrahydroquinolines fused with <i>γ</i>-lactone moiety

255th National Meeting (2018)

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Asymmetric catalyzed cycloaddition via copper-allenylidene process for preparation of tetrahydroquinolines fused with γ-lactone moiety