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

Abstract

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. α-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 α-amino boronates with an exceptionally high level of site-selectivities (up to 300:1). A wide variety of highly functionalized secondary and tertiary α-amino boronates are formed in generally good to excellent yields, thanks to the mildness of 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 of B­(MIDA) is also found.

Recent advances in the synthesis and reactivity of MIDA boronates

“…81 The Wang group also reported a boryl-dictated site-selective intermolecular allylic and propargylic C–H amination to afford α-amino boryl compounds in good yield and high regioselectivity (Scheme 12(c)). 82 Again, the stabilization of the adjacent positive charge by the B(MIDA) group is the key for the stereoselective ene reaction followed by a 2,3-sigmatropic shift to access α-amino MIDA-boron compounds. Recently, the Yudin group reported Lewis acid-promoted Boyer–Schmidt–Aube lactam ring expansions using azidomethyl MIDA boronate and cyclic ketones to afford diverse constrained α-amido-MIDA-boron compounds in good yields (Scheme 12(d)).…”

beta-Silicon Effect Enables Metal-Free Site-Selective Intermolecular Allylic C−H Amination

“…[23][24][25][26][27] We have recently developed a site-selective allylic C-H functionalization reaction guided by electron-donating B(MIDA) (N-methyliminodiacetyl boronate) moiety. 28 The capability of B(MIDA) to stabilize the developing positive charges at β position was proposed to be key for both reactivity and regio-selectivity. 29,30 This method was based on Sharpless's pioneering work in 1976 on metal-free allylic C-H amination of simple alkenes using stoichiometric in situ generated diimidoselenium reagent, [31][32] and more recently Michael's catalytic version using simple sulfonamides as nitrogen sources in combination of a hypervalent iodine oxidant.…”

Catalyst-Enabled Stereodivergence in Photochemical Atom Transfer Radical Addition (ATRA) of α-Iodoboronic Esters to Alkynes

“…We have a keen interest in synthesizing and applying allylboron molecules. − The recent advancements in boron-stabilized alkyl radicals ,− have inspired us to explore the potential of α-boryl radicals in synthesizing allylborons through a unique C–C bond formation approach. Recently, several metal-catalyzed , or photochemical , cross-coupling reactions have elegantly demonstrated this strategy using α-haloboronic esters as borylmethyl reagents, where the halogen acts solely as the leaving group.…”