Oxidative Difunctionalization of Alkenyl MIDA Boronates: A Versatile Platform for Halogenated and Trifluoromethylated α‐Boryl Ketones

Abstract

The synthesis of halogenated and trifluoromethylated a-boryl ketones via ao ne-pot oxidative difunctionalization of alkenyl MIDAb oronates is reported. These novel densely functionalizedorganoborons bearing synthetically and functionally valuable carbonyl, halogen/CF 3 and boronate moieties within the same molecule are synthetically challenging for the chemist, but have great synthetic potential, as demonstrated by their applications in as traightforwards ynthesis of borylated furans.The generality of this reaction was extensively investigated. This reaction is attractive since the starting materials,alkenyl MIDAboronates,a re easily accessible.Organoborons are among the most frequently used compounds in organic synthesis and organometallic chemistry, [1] with uses in other fields such as medicine and materials science, [2] enabling diverse and useful chemical transformations,w ith some of the most well-known and important examples being the Suzuki-Miyaura [3] and Chan-Evans-Lam [4] couplings,t he Petasis reaction [5] ,a nd the Hayashi-Miyaura conjugate addition. [6] Despite their importance,t he preparation of organoborons is not trivial in organic synthesis and this is particularly true for multi-functionalized organoborons consisting of sensitive functional groups. [1, 2] With regards to enolizable carbonyls that can generate boron enolates,t here is ar apid equilibrium between the O-and Cbound forms,with the latter being much less thermodynamically stable because of the stronger OÀBb onds over CÀB bonds. [7] Hence,t he formation of C-boron enolates (a-boryl carbonyls) provides ag reater challenge to the synthetic chemist. [8] However,t hey have potentially good synthetic value because they are kinetically amphoteric,m eaning that they contain an ucleophilic site adjacent to an electrophilic center (the nucleophilic boronate and the electrophilic carbonyl) and hence exhibit multiple modes of reactivity. [9]

Stereoselective Direct Chlorination of Alkenyl MIDA Boronates: Divergent Synthesis of E and Z α‐Chloroalkenyl Boronates

“…[10] Theu se of sp 3 -B MIDAb oronates, [11] which are typically bench-top and chromatographically stable solids, [12] circumvents potential C-to-O 1,3-boryl migration, and was the key to successful synthesis.T his result suggests the possibility of assembling a-haloalkenyl boronates through the direct halogenation of the corresponding alkenyl MIDA boronates.I ft his could be successfully conducted, the resulting a-haloalkenyl MIDAb oronates,w ith the boron presented in its protected form, might serve as ideal synthons for chemoselective iterative coupling reactions. [10] Theu se of sp 3 -B MIDAb oronates, [11] which are typically bench-top and chromatographically stable solids, [12] circumvents potential C-to-O 1,3-boryl migration, and was the key to successful synthesis.T his result suggests the possibility of assembling a-haloalkenyl boronates through the direct halogenation of the corresponding alkenyl MIDA boronates.I ft his could be successfully conducted, the resulting a-haloalkenyl MIDAb oronates,w ith the boron presented in its protected form, might serve as ideal synthons for chemoselective iterative coupling reactions.…”

“…We have recently developed an oxidative difunctionalziation of alkenyl N-methyliminodiacetyl (MIDA) boronates for the synthesis of halogenated and trifluoromethylated a-boryl ketones. [10] Theu se of sp 3 -B MIDAb oronates, [11] which are typically bench-top and chromatographically stable solids, [12] circumvents potential C-to-O 1,3-boryl migration, and was the key to successful synthesis.T his result suggests the possibility of assembling a-haloalkenyl boronates through the direct halogenation of the corresponding alkenyl MIDA boronates.I ft his could be successfully conducted, the resulting a-haloalkenyl MIDAb oronates,w ith the boron presented in its protected form, might serve as ideal synthons for chemoselective iterative coupling reactions. [13] To realize such ap rocess,h owever,t he following potential challenges must be addressed.…”

Recent advances in the synthesis and reactivity of MIDA boronates

“…38 b Next, in 2016, Wang and his co-workers reported the oxidative functionalization of alkenyl MIDA boronates to access halogenated and trifluoromethylated α-boryl ketones (Scheme 3(b)-iii). 39 It was observed that the reaction goes through the radical cation intermediate, which was generated by the oxidation of the alkene via the SET process. Later, in 2018, the Yudin group explored the Wacker oxidation of alkenyl MIDA boronates which afforded α-boryl ketones in high yield (Scheme 3(b)-iii).…”