| Abstract
| - Boronic acid-containing molecules are employed in a broad range of biological, medicinal, andsynthetic applications. These compounds, however, tend to be difficult to handle by solution-phasemethods. Herein, this problem is addressed with the development of the first general solid-phaseapproach for the derivatization of functionalized boronic acids. This approach is based on the useof a diethanolamine resin anchor that facilitates boronic acid immobilization by avoiding the needfor exhaustive removal of water in the esterification process. The immobilization of a wide varietyof boronic acids onto N,N-diethanolaminomethyl polystyrene (DEAM-PS, 1) can be performed withinminutes by simple stirring in anhydrous solvents at room temperature. Evidence for the formationof a bicyclic diethanolamine boronate with putative N−B coordination was shown by 1H NMRanalysis of DEAM-PS-supported p-tolylboronic acid. The hydrolytic cleavage of the same modelboronic acid from the DEAM-PS resin was studied by UV spectroscopy. Hydrolysis and attachmentwere shown to occur under a rapidly attained equilibrium, and a large excess of water (>32 equiv)is required to effect a practically quantitative release of boronic acids from DEAM-PS. Despitetheir relative sensitivity to water and alcohols, DEAM-PS-bound arylboronic acids functionalizedwith a formyl, a bromomethyl, a carboxyl, or an amino group can be transformed in good to excellentyields into a wide variety of amines, amides, anilides, and ureas, respectively. Ugi multicomponentreactions on DEAM-PS-supported aminobenzeneboronic acids, derivatization of multifunctionalarylboronic acids, and sequential reactions can also be carried out efficiently. These new DEAM-PS-supported arylboronic acids can be employed directly into resin-to-resin transfer reactions(RRTR). This type of multiresin process helps eliminate time-consuming cleavage and transferoperations, thereby considerably simplifying the outlook of combinatorial library synthesis bymanual or automated means. This concept was illustrated by a set of optimized procedures for theSuzuki cross-coupling and the borono-Mannich reactions.
|
