Synthesis of Aminoboronic Acid Derivatives from Amines and Amphoteric Boryl Carbonyl Compounds

Abstract

Herein, we demonstrate the use of α‐boryl aldehydes and acyl boronates in the synthesis of aminoboronic acid derivatives. This work highlights the untapped potential of boron‐substituted iminium ions and offers insights into the behavior of N‐methyliminodiacetyl (MIDA) boronates during condensation and tautomerization processes. The preparative value of this contribution lies in the demonstration that various amines, including linear and cyclic peptides, can be readily conjugated with boron‐containing fragments. A mild deprotection of amino MIDA‐boronates enables access to α‐ and β‐aminoboronic acids in high chemical yields. This simple process should be applicable to the synthesis of a wide range of bioactive molecules as well as precursors for cross‐coupling reactions.

Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors

“…1 . Our recent studies of borylated iminium ions 21 opens doors to run a wide range of multicomponent reactions with potential to expand the accessibility of heteroatom-rich organoboron compounds. Condensation of α-boryl aldehydes 1a – g with primary amines led to borylated iminium ions 2a – g (Fig.…”

“…2a ). Under reductive conditions, we were able to access β-amino(MIDA)boronates 3 containing the BCH 2 CH 2 N connectivity (Supplementary Methods) 21 , which have been shown to play important roles in catalysis 33 . Building on this observation, we were curious to evaluate the behavior of borylated iminium ions in multicomponent reactions.…”

“…6a ). We prepared an analogue lacking the nitrile group – 11a – using our previously reported reductive amination protocol 21 (Supplementary Methods). We also synthesized the control without boron 11b using the same method in Fig.…”

“…Inspired by the impact of β-amino acids and β-peptides on contemporary science 17 , 18 , we questioned the potential significance of homology in aminoboronic scaffolds and turned to amphoteric boron-containing compounds as the enabling building blocks. The goal of our work was to build upon facile α-aminoboronic acid synthesis 19 , 20 and the recently demonstrated stability of β-aminoboronic acids 21 .…”

Recent Advances in the Synthesis of Acylboranes and Their Widening Applicability

“…9b However, this venue remained unexplored until 2016, when Yudin et al performed reductive amination of acyl MIDA-boronates to provide aminoboronic acid derivatives. 25 They were able to prove the formation of the imine intermediate through NMR experiments, but could not isolate it due to C–N migration of the boryl moiety. In 2018, the Bode group made a significant contribution to the field of acylborane chemistry by reacting KATs with amines to yield a new class of compounds, namely trifluoroborate-iminiums (TIMs) ( Scheme 8 , entry 1a).…”