A-aminoboronic esters

Compound 51 was found to be unstable and difficult to purify, as described in the literature [93—95]. Therefore, 51 was not isolated, but was instead converted to the stable pinacol 1-acetamido-l-hexylboronate derivative 52. However, the acylated derivative 52 could not be purified by column chromatography as it was destroyed on silica gel and partially decomposed on alumina. Fortunately, we found that it dissolves in basic aqueous solution (pH > 11) and can then be extracted into diethyl ether when the pH of the aqueous layer is 5—6. Finally, pure 52 was obtained by repeated washing with weak acids and bases. It should be mentioned here that exposure to a strongly acidic solution, which also dissolves compound 51, results in its decomposition. Compared with other routes, the present two-step method involves mild reaction conditions (THF, ambient temperature) and a simple work-up procedure. It should prove very useful in providing an alternative access to a-aminoboronic esters, an important class of inhibitors of serine proteases. 

Scheme1.2 Application of the Matteson asymmetric homologation to the synthesis of chiral a-aminoboronic esters.

In general, the diboration of alkenes with [Pt(dba)2] required 50 while the use of [Pt(NBE)2] or [Pt(COD)2] (NBE = norbomene, COD = 1,5-cyclooctadiene) as precursors could diborate alkenes at room temperature." The reactions proceed smoothly to give 1,2-diborylaIkanes in high yield, and the catalysts were compatible with common functional groups. Further developments in the area by Baker showed that [Pt(COD)Cl2] could efficiently activate B2cat2 and promote the diboration of terminal alkenes, vinylarenes, alkynes, and aldimines (Scheme 9). The last example was a great advance because it represented the first direct approach toward a-aminoboronate esters. 

Mann G, John KD, Baker RT. Platinum catalyzed diboration using a commercially available catalyst diboration of aldimines to a-aminoboronate esters. Org Lett. 

Peptide a-oxo acids, a-oxo esters, and a-oxoamides are also potent inhibitors of cysteine and serine proteases. Oxidation of peptide a-substituted carboxylic acid derivatives provides a general route to these compounds (Section 15.1.5). Peptide hydroxamic acids have been shown to be inhibitors of metalloproteinase and some have been reported to have antibiotic, anticarcinogenic, and antiviral activities. Peptide hydroxamic adds may be prepared by solution and solid-phase methods using a variety of resins (Section 15.1.6). a-Aminoboronic acids may be prepared by several routes and are reported to be inhibitors of aminopepti-dases. Procedures have been developed for their incorporation into peptides (Section 15.1.7). 

This worked well [(2,6-(i-Pr)rPh]N=CHPh and (2,6-MerPh)N=CHPh gave 94 and 79% diboration, respectively, but significantly limited the molecular diversity of the resulting alpha-aminoboronate esters. Our third strategy arose from an observation that an ortho-methoxyphenyl substituent on the imine nitrogen yielded no diboration product. We presumed this was due to a substrate directing effect, and use of this substituent on the imine carbon then allowed us to diborate a number of N-alkylaldimines in good yield (Equation 7). 

Thus formed, organometallics are trapped with tiialkyl borates to produce whether the desired arylboronic [149-151,153] or diarylboronic esters [152], depending on the reaction conditions discussed above. The diarylboronic acids have also been successfully used in the Pd(PPh3)4-catalysed SM reactions with aryl triflates, under the standard conditions [152]. Beside trialkyl borates, A,A-dimethylaminoboron bromide has been trapped with organolithiums to give an unstable bis-aminoboronate 349, which, upon esterification with pinacol, gave the 1,4-phenylene-bis-pinacolato boronate (266) in 21% overall yield [154], Scheme 50. 

FIGURE 12. Coordinative linear polymers based on boronate ester formation result from (a) ditopic coordination of pyridyl boronic acids to bis-diol functionalized porphyrins and (b) through coordinative interactions between rhodoximes and 3-aminoboronic acid. 

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