Radical cyclization reactions are recognized as a powerful tool for the synthesis of natural products and bioactive organic compounds. These reactions often proceed with high stereoselectivity and functional group tolerance that could not be accomplished by other polar reactions. Various radical cyclizations in connection with concomitant functionalization such as oxidation, azidation, and cyanation have been developed; however, comprehensive radical cyclizations including C–B bond formation have not been reported. Organoboron compounds are versatile intermediates for synthetic organic chemistry because the boryl group can be converted to various functionalities through stereoselective oxidation, amination, and carbon–carbon bond formation. We reported a copper(I)-catalyzed boryl substitution in 2012. Our mechanistic study suggested that the reaction should proceed through a radical reaction pathway. In this work, we developed the first stereoselective borylative radical cyclization: borylation of alkyl halides bearing allyl ether moiety successfully provide the product containing saturated heterocyclic moiety. The copper(I)-catalyzed reaction of the alkyl halides with an allylic ether structure potentially competes with allylic boryl substitution. Therefore, we first conducted the investigation for the controlling chemoselectivity between the radical cyclization and the allylic substitution under the borylation conditions. After the screening of the ligand, we found that the reactions using PCy3, (2-hydroxyphenyl)diphenylphosphine (L1) or bathophenanthroline gave the borylative radical cyclization reaction products in high yield with excellent selectivity. In contrast to this, the reaction using Xantphos ligand exclusively provided the allylic boryl substitution product. The reaction could also be applied to a borylative Ueno-Stoke cyclization of α-haloacetals. The borylation products containing an acetal moiety were obtained in good yield with high stereoselectivity. Furthermore, the borylation products could be transformed to various organic compounds through oxidation, amination, and C–C bond forming reaction.

Stereoselective borylative radical cyclization with copper(I) catalyst

253rd National Meeting (2017)

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