Diethanolamine boronic esters

In the Suzuki strategy 138 was treated with trityl chloride to afford amine 139 in 84% yield (Scheme 4.29) (Todo et al., 2000). Metal-halogen exchange of 5-bromoisoindoline 139 was achieved using w-butyl lithium at — 65°C to deliver an intermediate organolithium species that was trapped with triisopropylborate to afford the boronic acid upon work-up. Further treatment of the boronic acid with diethanolamine gave diethanolamine boronic ester 140 (Hayashi et al., 2002). Presumably, the diethanolamine boronic ester was formed for stability reasons, as a given diethanolamine boronic ester tends to be less... 

The SM reactions are eompatible with the solid-phase synthesis what is applied in the combinatorial chemistry [95,97]. The arylboronic acids can be immobilized on the polystyrene eontaining diethanolamine-moieties by forming boronate esters XXV. A wide variety of thus bounded arylboronic acids bearing a bromomethyl, carboxylic, amino or aldehyde-group have been converted by N- or O-alkylation, amidation, reductive alkylation and some other reactions, to amines, esters, amides, ureas, etc [96]. The resulting arylboronic acid can be regenerated from the resin by simple... 

Scheme 7 Cleavage of Pinacol Esters of Boronic Acids by Exchange with Diethanolamine...

Pinanediol esters cannot be readily displaced by treating with diethanolamine. A convenient method of removing either pinanediol esters or pinacol esters for boronic acids that are insoluble in ethers and are readily soluble in water has been developed. 34 The boronic acid ester, e.g. 21, is incubated with a hydrophobic boronic acid such as phenylboronic acid 34 in a rapidly stirred mixture of water and ether (Scheme 8). After 3 hours, the phases are separated and the aqueous phase is concentrated to give the free boronic acid 22. In this case the reaction is driven to completion by the greater solubility of the free boronic acid in the aqueous phase and the greater solubility of the pinacol ester of phenylboronate in the ether phase. This procedure has also been used to remove the pinanediol ester from Ac-D-Phe-Pro-boroArg-pinanediol 34 (see Section 15.1.7.5). 

Cyclic boric acid esters derived from triethanolamine (Figure 9.11) or diethanolamine can be stabilized toward hydrolysis by an intramolecular, boron-nitrogen coordination bonding. The blockage of the empty-orbital on the boron atom can alleviate hydrolysis. This effect has been used to prepare... 

Pyridine 2-boronic acid is rather unstable (unlike the 3- and 4-isomers) and can only be isolated as esters, iV-substituted diethanolamine esters being the most stable. A possible rationale for this instability may be the parallel with the mechanism for the ready decarboxylation of pyridine 2-carboxylic acid via a transient ylide intermediate (8.11). 

Mild methods were known in some other specific instances. The (R,J )-2,3-butane-diol ester of (l-chloro-2-methylpropyl)boronic acid with diethanolamine yielded the crystalline diethanolamine ester [13]. DICHED (a-benzyloxyalkyl)boronates have been cleaved with TAPS buffer [a water-soluble gem-tris(hydroxymethyl) compound] and excess base [74]. However, these methods were inefficient and not general. 

A and n.m.r. study of redistribution phenomena of fluorine and chlorine monofunctional three- and four-co-ordinated boron centres has appeared. and C n.m.r. have been used to study the stereodynamics of enantiomerization in bis(di-isopropylamine)aminoboranes, to study 1,3,2-diazaboracycloalkanes and phenylborane derivatives, and to study three reversible exchange processes in diphenylboronic acid diethanolamine ester. A variety of spectral data (m.s., i.r., and C, and n.m.r.) have been used to investigate the molecular structure of (l-imidazolyl)diorganylboranes. Crystal structures have been published for the following molecules 4-methyl-2-phenyl-(3/f)-l, 3,5,2-oxadiazaboroline, hydrazinium tetraethynylborate... 

Like borinic adds, boronic acids are weak adds and are readily charao-terized as cyclic derivatives such as diethanolamine esters (3.26) pyridine adducts of their anhydrides (3.27) or as benzodiazaboroles (3.28). 

The preparation of functionalized aryl boronic reagents can be achieved by directed metallation followed by a transmetallation of aryllithiums with organoboron compounds. Thus, Caron and Hawkins have described a directed ortho-metalla-tion of aryl neopentyl esters such as 1 for the synthesis of substituted ortho-horo-nyl neopentyl benzoates using lithium diisopropylamide (LDA) as the base and B(OiPr)3 as an in situ trap [3]. The crude boronic acids obtained by acidic hydrolysis were subsequently treated with ethanolamine and converted to stable diethanolamine complexes such as 2. This methodology allows the preparation of a new class of boronic acids with ortho-carbonyl substituents and other functionalities... 

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