Chemoselective oxidation of aryl organoboron systems enabled by boronic acid-selective phase transfer

Abstract

Chemoselective boronate formation and phase transfer allows chemoselective Brown oxidation of boronic acids in the presence of boronic esters.

Chemoselective Suzuki–Miyaura Cross‐Coupling via Kinetic Transmetallation

“…The BPin species were not observed to undergo phase transfer, consistent with previous studies. 19,21 In addition, under optimum (low H2O) conditions, diol equilibration (B, Scheme 4) was inhibited, maintaining ~95% integrity of the initial system -16.4:1 B(OH)2:BPin after 10 min. However, under biphasic conditions, equilibration was much more significant (2:1 B(OH)2:BPin within 10 min).…”

“…(2) Introduction of a bulk basic aqueous phase promotes phase transfer of boronic acid from the organic phase to the aqueous as its cognate boronate. 19 Assuming a largely organic phase bound Pd catalyst, 15,20 this lowers the concentration of boronic acid available for transmetallation in the organic phase, instead requiring a contrathermodynamic transfer of boronic acid boronate from the aqueous phase to the organic, 15,20 and thereby negatively impacting both reaction efficiency and selectivity. Spectroscopic investigations supported these hypotheses -the key solution events are shown in Scheme 4.…”

Chemoselective Suzuki–Miyaura Cross‐Coupling via Kinetic Transmetallation

“…However,under identical reaction conditions in acompetitive system notable chemoselectivity was recorded (Scheme 2b). [18,19] Competitive coupling of the in situ generated BPinderived boronic acid erodes selectivity and thus must be controlled in order to exploit any natural kinetic advantage (see below). 9:1s electivity exhibited in this nonoptimized system.…”

“…Importantly,i n order to rule out any effects of the p-Me substituent, the corresponding experiment using Ph-B(OH) 2 and p-tol-BPin was conducted, affording comparable results (95:5 3:5). [19] Assuming alargely organic phase bound Pd catalyst, [15,20] this lowers the concentration of boronic acid available for transmetallation in the organic phase,i nstead requiring ac ontra-thermodynamic transfer of boronic acid boronate from the aqueous phase to the organic, [15,20] and thereby negatively impacting both reaction efficiency and selectivity.S pectroscopic investigations supported these hypotheses,t he key solution events are shown in Scheme 4. [20] 1) Equilibration increased as H 2 Oi ncreased, thereby reducing selectivity due to the formation of acompeting boronic acid from the BPin component (see Scheme 3).…”

“…[19,21] In addition, under optimum (low H 2 O) conditions,d iol equilibration (B,S cheme 4) was inhibited, maintaining ca. In contrast, in ah ighly biphasic medium (50/50 1,4-dioxane/ H 2 O), boronic acid phase transfer was observed to begin immediately (< 5min).…”