Amino and Amido Substituents

The first amino substituted boronic esters were tertiary amines derived from dibutyl (iodomethyl)boronate and secondary amines [58]. Mysteriously, ammonia did not yield the simple (aminomethyl)boronic ester, but ilure of a reaction does not prove anything. Subsequent rechecking with primary, secondary, and tertiary amines as reactants showed that primary amines with dibutyl (iodomethyl)boronate did not yield isolable primary (aminomethyl)boronic esters [59]. The tertiary amines and quaternary ammonium salts derived from secondary and tertiary amines were stable and easily isolable. 

In an unrecorded experiment, D. Majumdar observed that lithio-2,2,6,6-tetram-ethylpiperidide displaced chloride ion from an (a-chloroalkyl)boronic ester, albeit in mediocre yield. It was then recognized that lithiohexamethyldisilazane, LiN(SiMe3)2, should provide the requisite primary amino substituent in protected form. This expectation proved correct, and desilylation to the (a-aminoalkyl)boronic acid proved 

An application that takes advantage of the deboronation is described in Section 8.3.8. 

The free amino boronic acid CH3CH(NH2)B(OH)2, an alanine analog, survives for a few hours after its N-silylated-O-isopropyl protected form contacts water. It is an inhibitor of Bacillus stearothermophilus alanine racemase and Salmonella typhimurium D-alanine D-alanine ligase [66]. 

Once the stability problem with (a-aminoalkyl)boronic esters was understood, several research groups began searching for possible pharmaceutical applications. These studies are covered in Chapter 13. 

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