A Convergent, Stereoselective Route to Trisubstituted Alkenyl Boronates

Abstract

A modular, stereoselective route to trisubstituted (Z)-alkenyl (MIDA)boronates is described, consisting in the radical addition-fragmentation of dithiocarbonates to 2-(MIDA)boronyl-3-(2'-fluoro-pyridyl-6'-oxy)-alkenes. The bulky (MIDA)boronate ensures a highly stereoselective fragmentation that is enhanced by the poor stabilization of the radical adjacent to the tetravalent boron atom. The vinyl boronate precursors are prepared from propargyl alcohols by copper-catalyzed regioselective hydroborylation of their fluoropyridoxy derivatives, with the fluoropyridine acting as an internal directing group.The importance of organoboron compounds to organic synthesis, medicinal chemistry, and material sciences is overwhelming. 1 Indeed, the Suzuki-Miyaura cross-coupling ranks in the top five reactions used by medicinal chemists in drug discovery and development. 2 The stability, low toxicity, and versatile reactivity of organoboronates are considerable advantages that make them almost ideal synthetic intermediates.

Synthesis of (Z)-alkenyl boronates via a copper(i)-catalyzed linear-selective alkylboration of terminal allenes

“…It should be noted that the types of alkenyl boronates investigated here are inaccessible via other transition-metal-catalyzed proto- and hydroboration reactions of alkyne substrates, although multi-step procedures have been reported. 6–12 Regardless, the sec -alkyl iodide iodocyclohexane is not suitable for this reaction (<5%). 17 e…”

“…7,8 The recent development of alternative synthetic methods has expanded the variety of accessible alkenyl boronates; however, the diversity of aliphatic ( Z )-alkenyl boronates remains limited. 9–12 Here, we planned to synthesize alkenyl boronates via a copper( i )-catalyzed three-component coupling between terminal allenes, alkyl halides, and a diboron reagent, i.e. , an intermolecular alkylboration of allenes (Scheme 1c).…”

“…7,8 The recent development of alternative synthetic methods has expanded the variety of accessible alkenyl boronates; however, the diversity of aliphatic (Z)-alkenyl boronates remains limited. [9][10][11][12] Here, we planned to synthesize alkenyl boronates via a copper(I)-catalyzed threecomponent coupling between terminal allenes, alkyl halides, and a diboron reagent, i.e., an intermolecular alkylboration of allenes (Scheme 1c). 13 With control over the regio-, stereo-, and chemoselectivity, nucleophilic borylation of the allene moiety and subsequent alkylation can be expected to furnish (Z)-alkenyl boronates that bear two different alkyl groups.…”

Boron-Promoted Deprotonative Conjugate Addition: Geminal Diborons as Soft Pronucleophiles and Acyl Anion Equivalents

“…To investigate the utility of the diboryl conjugate addition–oxidation approach in enabling access to rare 1,4-dicarbonyls, we became interested in developing a synthetic route to γ-keto acylborons (Scheme ). The unique chemical reactivity and applications of acylborons in organic synthesis and bioconjugation have inspired several creative synthetic methods. , While the α-keto and β-keto acylborons can be prepared using several approaches, methods to access γ-keto acylborons are scarce . Inspired by our recently developed route to MIDA acylborons, , the geminal diboron motif in the conjugate addition product 3z (Scheme ) was successfully transformed into unsymmetrical diboron 6 .…”

Recent advances in the synthesis and reactivity of MIDA boronates

“…Besides, this reactivity was further utilized by the Zard group in the synthesis of trisubstituted alkenyls. 75 Then, in 2017, the Woz ´niak group disclosed a methodology for the alkylation of unsaturated MIDA boronates that uses Ru(bpy) 3 Cl 2 as the photoredox-catalyst. The reaction proceeds through the atom transfer radical addition (ATRA) pathway using various perfluoroalkyliodides (Scheme 11(b)).…”