Boronic ester reversibility

The preorganisation approach (b) involves formation of strong reversible covalent arrangements (boronate esters, imines, ketals) of the monomers... 

Severin and coworkers reported (146) the reaction of tris(2-aminoethyl)amine and 4-formylphenylboronic acid with penta-erythritol to give, via multicomponent assembly, the boronic acid based macrobicyclic cage 35 (Fig. 25). The cage has the form of an ellipsoid with a diameter of 20.5 A and binds two Cud) ions in a fashion similar to the smaller tren-based cryptands. The reversible formation of boronic esters has also been employed to build other hollow structures such as nanotubes (147) and porous covalent organic frameworks (148,149). 

Covalent polymers with reversible properties arising from dynamic covalent bonds such as disulfide exchange reaction [47 9], transesterification [50,51], transetherification [52], and boronate ester formation [53] were reported without respect to DCC. These studies should involve DCLs in... 

As a conseqnence of their superior stability, many types of allylic boronates can be isolated and purified. It should be noted that most pinacol allylic boronic esters and other bnlky esters are stable to hydrolysis and can be conveniently pnrified by chromatography on silica gel. A potential pitfall of all allylic boron componnds is their stereochemical integrity, and snbstituted allylic boranes are known to nndergo reversible borotropic rearrangements at temperatures above —45° (see Eq. 12, M = Eor this reason, allylic boranes are nor-... 

S)-Glycerol-l-rf results if the order of introduction of hydrogen and deuterium on C-1 is reversed. Thus, the common intermediate 1 with the lithio derivative of deuterated dibromomethane forms the deuterated broino boronic ester 4. It is not necessary to use more than one molar equivalent of dibromomethane-t/2. With an unlabeled hydride source such as lithium tricthylborohydride, 4 yields the (lS, 2/ )-l-deutero boronic ester 5, which is deboronated and deprotected to (l/f,25,)-giycerol-l-d . Labeled glycerol has been made in batches of 0.3 - 0.8 g by this route. 

Boronic acids can be reversibly esterified with resin-bound diols (Figure 3.15). The resulting boronic esters are stable under the standard conditions of amide bond formation, but can be cleaved by treatment with water under acidic or neutral conditions to yield boronic acids. Treatment of the resin-bound boronic esters with alcohols yields the corresponding boronic esters [197]. Resin-bound boronic esters are suitable intermediates for the Suzuki reaction [198], Treatment with H202 leads to the formation of alcohols (Entry 8, Table 3.36), while treatment of resin-bound aryl boronates with silver ammonium nitrate leads to the conversion of the C-B bond into a C-H bond (Entry 14, Table 3.46). 

Attachment of the alkene monomers to the template (Fig. 6.5), which must be reversible - readily formed and readily broken - to permit removal of the template after polymerisation, can generally be accomplished in two ways covalently or non-covalently. While the latter interactions (ionic, hydrophobic, n-n, hydrogen bonding) can easily be reversed, there is less scope for reversible covalent linkages. One of these is the formation of boronic esters - from boronic acid units of the monomers and OH groups of sugar templates. 

Fig. 9 (a) Reversible synthesis of a bisiminoboronate-guanosine derivative from guanosine and a bisiminoboronic acid, (b) Dynamic polymeric networks based on reversible boroxine formation, (c) Formation of a macrocycle in a [4 + 4 + 2] condensation via simultaneous reversible formation of imine bonds and boronic esters... 

Boronic acids (5a) were among the first examples of low-molecular-weight, reversible inhibitors of serine proteinases [151, 152]. Significant inhibition was initially demonstrated against a-chymotrypsin. Unlike the carbonyl-derived reversible inhibitors, which require a polypeptide or peptide-like chain, activity was found with simple alkylboronic acids (e.g. the value for PhCH2CH2B(OH)2 with a-chymotrypsin was = 40 //M) [153], Weak inhibition of elastase (PPE) was first reported for a series of arylboronic acids, for example, (10-1) [123]. Some of the boron-based inhibitors Figure 2.5) were tested as either the difluoroboranes (5b) or as the pinacol boronate esters (5c). These modifications were employed because they were more readily synthesized and/or purified than the boronic acids. For both of these derivatives inhibition was shown to be due to in situ hydrolysis to the parent boronic acid (5a) [154, 155]. 

In fact, one boronic acid can reversibly form a boronate ester with two OH groups (one diol group), and one diboronic acid can immobilize two suitably positioned diol units to form a saccharide-containing macrocycle. Selectivity can be achieved by controlling the relative spatial position of the two boronic acids in relation to the cis-diol moieties on the saccharide. A given monosaccharide possesses at least two binding sites that differ from other monosaccharides. 

The boronic acid 20 reported by Shinkai is a rare example of an enantiopme chiral redox-active receptor." It was found to bind linear and cyclic sugars in aqueous solution at neutral pH due to the reversible reaction between the boronic acid moiety of the protonated ferrocene receptor and the sugar to form a boronate ester. Electrochemical studies revealed that complexation imparted cathodic (ca. - 50 mV) shifts in the Fc /Fc redox couple. Interestingly, moderate enantioselectivity was observed in that (+ ) — 1 bound the linear saccharide D-sorbitol more strongly than L-sorbitol (ATd/AIl = 1-4). However, differences in the electrochemical response to the binding of these enantiomers by 20 were not apparent. 

In the covalent approach (Figure 2), a polymerizable derivative of the template is obtained by linking the template with a vinyl functional monomer via a strong reversible covalent bond (e.g., boronate esters, Schiff bases, or ketal). The derivatized print molecule is then radical copolymerized with an excess amount of a cross-linking agent, using either thermal or photochemical radical initiation. Reaction conditions are... 

Kobayashi investigated a self-assembled boronic ester cavitand capsule for photochemical reaction of 2,6-diacetoxyanthracene. Tsuda found a self-assembled helical anthracene nanofiber in a vortex. Chou examined rotational behaviors and fluorescence energy transfer of N-l- and N-2-anthryl succinimide derivatives. " Reversible photoinduced twisting of molecular crystal microribbons via [4 - - 4] photocycloaddition of 9-anthra-cenecarboxylic acid. Reversible single walled carbon nanotubes of 1,3-bis(9-anthracenylmethyl)imidazolium chloride was examined as a functionalized anthracene salts.Karatsu reported the intramolecular photodimerization of 9-substituted anthracene derivatives (253) tethered by oligosilanes giving [4 + 4] and [2 - - 4]cycloadducts (254), (255), and (256). ... 

In comparison to abundant examples of noncovalent supramolecular assemblies,relatively few structures have been built with strong covalent bonds. This is due to the fact that normal covalent bonds are not easily broken and reformed. One can manipulate the temperature and conditions so that the formation of stable imines, esters, disulfides, hydrazones, and boronate esters is reversible. Some examples of these covalent self-assembled systems include disulfide hosts and covalent organic frameworks. ... 

Boronic ester formation is an alternative process suitable for dynamic covalent chemistry. Nishimura and Kobayashi made use of the reversible condensation between an aryl-boronic acid and catechol in the development of dynamic hemicarcerand 42. Heating a 2 4 mixture of a tetra-boronic acid cavitand and biscatechol 43 resulted in the quantitative formation of 42. Again, the high efficiency is a result of the proper choice of the building blocks. Biscatechol 43, which in its lowest energy conformation is a perfect 120° ditopic bis-l,2-diol unit, is complementary to the orientation of the boronic acids in the cavitand building block to yield 42 with little or no strain. 

Scheme 1 The rapid and reversible formation of a cyclic boronate ester between a boronic acid and 1.2-diol.

The primary interaction of a boronic acid with a diol is covalent and involves the reversible and rapid formation of a cyclic boronate ester. An array of hydroxyl groups presented by saccharides provides an ideal architecture for these interactions and has led to the development of boronic acid-based sensors for saccharides (Scheme 1). 

Boronic acids can be used to sense diols, such as sugars, as well as amino acids. The binding mechanism is shown in Figure 7. Boronic acid reacts with 1,2- or 1,3- diols to produce stable 5- or 6-membered cyclic boronate esters. The removal of resultant water can make the reversible reaction go forward. This covalent but reversible interaction between boronic acid and c -diols provides a sensing tool for saccharides, which are difficult to detect in aqueous solutions. 

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