Aliphatic α‐Boryl‐α‐bromoketones: Synthesis and Reactivity

Abstract

A protocol for the preparation of α‐boryl‐α‐bromoketones from alkenyl MIDA boronates was developed and applied to functionalized aliphatic derivatives. The reaction sequence included regioselective hydroxybromination of olefin moiety, followed by oxidation of alcohol group with Dess–Martin periodinane. The target trifunctional boronate‐containing derivatives were obtained in up to 94 % yield over two steps starting from alkenyl MIDA boronates. In some cases, functional groups present in the substrate participated in the bromohydroxylation step via intramolecular nucleophilic attack at the bromonium cation leading to cyclic products. Additionally, the reactivity of aliphatic α‐boryl‐α‐bromoketones was illustrated by nucleophilic substitution at the α‐C atom and heterocyclization reactions.

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

“…11 Excellent conversion, high chemoselectivities (with dechlorinated byproducts in the range of 3-19%), and enantioselectivities of up to 94% enantiomeric excess (ee) values were achieved. In addition, the reaction with (1-bromo)-1-alkenyl)boronic esters (14) was also studied (Scheme 5B). 12 However, the special starting materials and the high hydrogen pressure bring the method some limitations for the application.…”

“…In 2020, Grygorenko and co-workers further expanded the product scope from aryl ketones to aliphatic ketones (20) through regioselective bromohydroxylation (19) followed by oxidation of the alcohol group with Dess-Martin periodinane (Scheme 7). 14 At around the same time, the Wang group also studied this halohydroxylation, including chloro-, bromo-and iodohydroxylation with the alkenyl MIDA boronates as the starting material (Scheme 8A). 15 Interestingly, a syn-addition process was detected using Cl + or Br + as the halogen source (22-a, 22-b), while trans-addition products were obtained when I + was employed (22-c).…”

Recent advances in the synthesis and reactivity of MIDA boronates

“…40 In 2020, the Grygorenko group also developed another synthetic protocol to synthesize a-brominated a-boryl ketones from alkenyl MIDA boronates (Scheme 3(b)-iv, v). 41 Here, the alkenyl MIDA boronate was subjected to bromination using NBS in THF/H 2 O (2 : 1) and furnished a-bromo b-hydroxy MIDA boronate as a single regioisomer. Further oxidation of the alcohol moiety using DMP (Dess-Martin Periodinane) in anhydrous CH 3 CN resulted in the formation of a-brominated a-boryl ketones.…”

Formyl MIDA Boronate: C1 Building Block Enables Straightforward Access to α‐Functionalized Organoboron Derivatives

“…[1,2] Over the last decade,l ots of efforts were put into synthesis of a-a nd b-functionalized boronates which were shown to be excellent building blocks for modular construction of heterocyclic compounds (Scheme 1A). [3][4][5][6][7][8][9][10][11][12] Among the mentioned boron-containing structural motifs, acylboron derivatives (Scheme 1B)a re known to be an emerging class of compounds with strong potential for novel synthetic applications. [13] Thef irst characterized acylboranes contained either adiamine ligand coordinated to the B-atom (type a) [14][15][16] or an N-heterocyclic carbene (type b).…”

“…Apart from elaboration of synthetic methods which utilize C−B bond transformation, development of new organoboron reagents which allow to achieve greater structural diversity of the target compounds presents another important objective . Over the last decade, lots of efforts were put into synthesis of α‐ and β‐functionalized boronates which were shown to be excellent building blocks for modular construction of heterocyclic compounds (Scheme A) …”