gem‐Difluorination of Alkenyl N‐methyliminodiacetyl Boronates: Synthesis of α‐ and β‐Difluorinated Alkylborons

Abstract

Organofluorine compounds are widely used in pharmaceutical, agrochemical, and materials sciences.T he syntheses and applications of fluorinated organoborons facilitate the rapid and modular assemblies of fluorine-containing molecules because of the versatility of C À Bb onds in diverse chemical transformations.R eported herein is am igratory geminal difluorination of aryl-substituted alkenyl N-methyliminodiacetyl (MIDA) boronates using commercially available Py·HF as the fluorine source and hyperiodine as the oxidant. The protocol offers facile access to a-a nd bdifluorinated alkylboron compounds,b oth of which have previously been challenging to prepare.M ild reaction conditions,b road substrate scope,g ood functional-group tolerance,and moderate to good yields were observed. The utility of these products is demonstrated by further transformations of the CÀBbond into other valuable functional groups.Scheme 5. Mechanistic studies and proposed mechanism.

Synthesis of β-Difluoroalkyl Azides via Elusive 1,2-Azide Migration

“…We first sought to establish conditions for the gem-difluorination and 1,2-azide migration reaction by using vinyl azide 1aa as a model substrate (Table 1). Subjection of 1aa to oxidative fluorination conditions employed for gem-difluorination and 1,2-aryl migration of styrenes 36 (pyridine,HF as fluorine source, bis(acetoxy)iodobenzene (PIDA) as oxidant in CH 2 Cl 2 at 25 C) afforded the 1,2-azide migration product 2aa in excellent yield (entry 1). An oxidant was essential (entry 2), whereas other potential fluorine sources (e.g., AgF, 43 CsF, 44 Et 3 N,HF 45 ) led to no reaction (entries 3-5).…”

“…39 However, with the exception of isolated examples involving benzyl ether (OBn) and sulfonamide (NHTs) groups, 40 these rearrangements proceed almost exclusively via arene migration. Under similar oxidative fluorination conditions (pyridine,HF and hypervalent iodine), 36 we report herein a conceptually novel 1,2-azide migration, which enable the efficient synthesis of a wide range of gem-difluorinated alkyl azides (Figure 1C). The migratory preference can be tuned through electronic effects, enabling a product switch in the reactions of a-aryl vinyl azides (i.e., azide migration versus arene migration).…”

“…via a gem-difluorination and 1,2-azide migration (Figure 1C). The related gem-difluorination and 1,2-aryl migration of styrenes, recently been described by Jacobsen 32,33 and others, [34][35][36][37][38] provides an efficient and powerful means to access the gem-difluoroalkyl motif, a useful bioisostere of common polar functional groups. 39 However, with the exception of isolated examples involving benzyl ether (OBn) and sulfonamide (NHTs) groups, 40 these rearrangements proceed almost exclusively via arene migration.…”

Regio- and stereoselective synthesis of tetra- and triarylethenes by N-methylimidodiacetyl boron-directed palladium-catalysed three-component coupling

“…Importantly, this moiety, as a protected form of boronic acid, is transformable to other functional groups under a one-pot deprotection/coupling reaction condition. Advances from us, and others have demonstrated that MIDA boron functionalized unsaturated systems (including alkenes [33][34][35][36][37][38][39][40][41][42] and alkynes [43][44][45][46][47][48][49][50] ) are intriguing synthons for boron-retentive transformations [51][52][53] . Specifically, Yudin and Dudding 54 , and Gueŕinot and Cossy 55 , have independently observed the unique electronic directing effect of MIDA boron in palladium-catalysed Heck reactions and Wacker oxidations of alkenyl MIDA boronates, respectively (Fig.…”

Fluorocyclization of Vinyl Azides for the Formation of 3‐Azido Heterocycles

“…To test the proposed strategy, we began our investigation by studying the oxyfluorination reaction of 1 d (Table 1). After intensive examination, we found that the desired 3‐azido heterocycle 2 d was obtained in 98% yield when using iodobenzene diacetate (PIDA, 1.5 equiv) as oxidant and pyridine ⋅ HF complex (Py ⋅ HF, 2.0 equiv) as fluorine source in dichloromethane (DCM) at 0 °C (entry 1) [13] . Replacing PIDA with iodosobenzene bis(trifluoroacetate) (PIFA) or iodosylbenzene (PhIO) resulted in lower yields (entries 2, 3).…”