Synthesis of Fluorinated Aminoalkylboronic Acids from Amphoteric α-Boryl Aldehydes

Our ongoing search for underdeveloped functional group combinations has brought to light alpha-fluorinated aminoalkylboronic acids, a new class of molecules featuring the B-CF linkage. These compounds can now be generated from secondary amines and alpha-boryl aldehydes through electrophilic fluorination of boryl enamines or enamides. Fluorinated beta-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 beta-aminoalkylboronic acids are stable over a wide pH range and are characterized by a pK(a) of 3.4, which is the lowest of any alkylboronic acid.