Deoxygenative Haloboration and Enantioselective Chloroboration of Carbonyls

Abstract

Deoxygenative difunctionalization of carbonyls affords a straightforward and effective route to construct geminal dual functionalized motifs. However, the research in this field is very challenging due to the strong bond dissociation energies of the C−O double bond or the subsequently formed C−O bond. Herein, we report a highly efficient deoxygenative haloboration of aldehydes to generate secondary α-haloboronates. Meanwhile, the difficult-to-obtain tertiary α-haloboronates can be also readily prepared via the same strategy with ketones. Furthermore, enantioselective chloroboration of carbonyls was successfully achieved to give chiral secondary or tertiary α-chloroboronates, the important intermediates to access enantioenrich multisubstituted stereocenters. These versatile products can be surprisingly attained through this simple and mild process with remarkable substrate scope expansion and functional group tolerance. Additionally, these reactions can proceed well on large scales, giving more practical values in the application.

Recent Advances in the Preparation and Asymmetric Transformation of α-Haloboron Compounds

“…To this end, very recently, we reported a very convenient and modular method to construct -haloboronates or chiral -chloroboronates via a deoxygenative difunctionalization of carbonyls (DODC) strategy. 23 We found that for the aldehyde (44-a), after the copper-catalyzed borylation, the in-situ formed intermediate can be easily converted into -chloroboronate product (46-a) in 90% yield by simple reaction with TMSCl With these conditions, a diverse set of aldehydes bearing various functional groups, even for those that are sensitive to strong bases or organometallic reagents, can be compatible, thus providing a protocol to synthesize complex skeletons (Scheme 15). Meanwhile, -bromo-and -iodoboronates can be conveniently accessed just by replacing the nucleophile TMSCl with TMSBr or TMSI.…”

Construction of α-Halogenated Boronic Esters via Visible Light-Induced C–H Bromination

“…4, 133.2, 130.6, 128.9, 128.1, 121.7, 84.6, 29.6, 24.73, 24.65; 11 4,4,5,5-tetramethyl-1,3,2dioxaborolane (11). Colorless oil; yield 83%, 29.9 mg; 1 H NMR (600 MHz, CDCl 3 ) δ 7.98 (s, 1H), 7.82−7.78 (m, 4H), 7.47−7.45 (m, 2H), 2.25 (s, 3H), 1.32 (s, 12H); 13 C{ 1 H} NMR (150 MHz, CDCl 3 ) δ 141.0, 132. 9,132.5,128.3,127.8,127.4,127.0,126.2,126.1,125.0,84.7,29.1,24.44,24.38;11 B NMR (193 2-(1-Bromo-1-phenylpropyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane (12).…”

Recent advances in the chemistry of α-oxylboronate reagents

“…Recently, halides (Cl, Br, and I) were used as nucleophiles in the transformation of the C–O bond in tertiary α-OBpin boronates to construct a series of α-haloboronates by the Xu group (Scheme 21). 37 With ketones as substrates, the difficult-to-obtain tertiary α-haloboronates could be readily obtained. Furthermore, chiral secondary or tertiary α-chloroboronates could be obtained successfully via enantioselective chloroboration of carbonyls, and the enantioselectivities and yields of the products obtained from aldehydes were excellent compared to those obtained from ketones.…”