Synthesis of Fluorinated Aminoalkylboronic Acids from Amphoteric α‐Boryl Aldehydes. Issue 30 (22nd June 2021)

• Record Type: Journal Article
• Authors: Soor, Harjeet S.; Diaz, Diego B.; Burton, Katherine I.; Yudin, Andrei K.
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 30(2021)
• Page Start: 16366
• Page End: 16371
• Publication Date: 2021-06-22
• Subjects: aminoalkylboronic acids -- electrophilic fluorination -- fluorine-containing boronic acids -- α-boryl aldehydes; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202104133
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Our ongoing search for underdeveloped functional group combinations has brought to light α‐fluorinated aminoalkylboronic acids, a new class of molecules featuring the B‐CF linkage. These compounds can now be generated from secondary amines and α‐boryl aldehydes through electrophilic fluorination of boryl enamines or enamides. Fluorinated β‐aminoalkylboronic acids show no signs of degradation under ambient conditions. We present evidence for the involvement of chair‐like motifs, favored over the acyclic forms by up to 1.7±0.1 kcal mol −1 in water and held together by an amine‐boronate hydrogen bond. Fluorinated β‐aminoalkylboronic acids are stable over a wide pH range and are characterized by a p K a of 3.4, which is the lowest of any alkylboronic acid. Abstract : Despite the prevalence of boron‐based therapeutics and inhibitors there is a dearth of methods to modulate oxidative stability of boronic acids. The introduction of fluorine atoms is known to increase oxidative stability of organic molecules, but fluoroalkyl groups connected to boron are unstable. Here we show that fluorinated aminoalkylboronic acids are stable within a wide range of pH values, along with evidence of cyclic and linear conformers at basic pH.