Boryl-Dictated Site-Selective Intermolecular Allylic and Propargylic C-H Amination

For internal alkenes possessing two or more sets of electronically and sterically similar allylic protons, the site-selectivity for allylic C-H functionalization is fundamentally challenging. Previously, the negative inductive effect from an electronegative atom has been demonstrated to be effective for several inspiring regioselective C-H functionalization reactions. Yet, the use of an electropositive atom for a similar purpose remains to be developed. alpha-Aminoboronic acids and their derivatives have found widespread applications. Their current syntheses rely heavily on functional group manipulations. Herein we report a boryl-directed intermolecular C-H amination of allyl N-methyliminodiacetyl boronates (B(MIDA)s) and propargylic B(MIDA)s to give alpha-amino boronates with an exceptionally high level of site-selectivities (up to 300:1). A wide variety of highly functionalized secondary and tertiary alpha-amino boronates are formed in generally good to excellent yields, thanks to the mildness the reaction conditions. The unsaturated double and triple bonds within the product leave room for further decorations. Mechanistic studies reveal that the key stabilization effect of the B(MIDA) moiety on its adjacent developing positive charge is responsible for the high site-selectivity and that a closed transition state might be involved, as the reaction is fully stereoretentive. An activation effect B(MIDA) is also found.

Automated summary

This study reports a boryl-directed intermolecular C-H amination of internal alkenes, resulting in highly functionalized alpha-amino boronates with exceptional site-selectivity. The reaction conditions are mild, and the reaction is fully stereoretentive, allowing for further decorations on the unsaturated bonds within the product.