Direct synthesis of B-allyl and B-allenyldiisopinocampheylborane reagents using allyl or propargyl halides and indium metal under Barbier-type conditions.

We report the first one-pot process for the asymmetric addition of allyl, methallyl, and propargyl groups to aldehydes and ketones using B-chlorodiisopinocampheylborane ((d)DIP-Cl) and indium metal. Under Barbier-type conditions, indium metal was used to generate allyl- and allenylindium intermediates, and subsequent reaction with (d)DIP-Cl successfully promoted the transfer of these groups to boron forming the corresponding chiral borane reagents. The newly formed borane reagents were reacted with aldehydes and ketones to produce the corresponding alcohol products in high yields and up to excellent enantioselectivity (98% ee). This method produced excellent enantioenriched secondary homoallylic alcohols from the allylation and methallylation of benzaldehyde. Using this method, the methallylation and cinnamylation of ketones afforded the highest enantioselectivities, while the propargylation of both aldehydes and ketones provided low enantiomeric excesses. In addition, this procedure provided the first synthesis of B-allenyldiisopinocampheylborane, which was characterized by (1)H and (11)B NMR spectroscopy. This is the first example of the direct synthesis of allylboranes that contained substitutions from the corresponding allyl bromide and indium, thereby expanding the utility of the DIP-Cl reagent. Hence, a general and straightforward route to these chiral organoborane reagents in one-pot has been developed along with the asymmetric Barbier-type allylation and propargylation of aldehyde and ketone substrates using these chiral organoborane reagents in subsequent coupling reactions.

Indium-mediated asymmetric Barbier-type propargylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents.

We report a simple, efficient, and general method for the indium-mediated enantioselective propargylation of aromatic and aliphatic aldehydes under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 90%) and enantiomeric excess (up to 95%). The extension of this methodology to ketones demonstrated the need for electrophilic ketones more reactive than acetophenone as the reaction would not proceed with just acetophenone. Using the Lewis acid indium triflate [In(OTf)(3)] induced regioselective formation of the corresponding homoallenic alcohol product from acetophenone. However, this methodology demonstrated excellent chemoselectivity in formation of only the corresponding secondary homopropargylic alcohol product in the presence of a ketone functionality. Investigation of the organoindium intermediates under our reaction conditions shows the formation of allenylindium species, and we suggest that these species contain an indium(III) center. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.

Indium-mediated asymmetric barbier-type allylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents.

We report a simple, efficient, and general method for the indium-mediated enantioselective allylation of aromatic and aliphatic aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 99%) and enantiomeric excess (up to 93%). Our method is able to tolerate various functional groups, such as esters, nitriles, and phenols. Additionally, more substituted allyl bromides, such as crotyl and cinnamyl bromide, can be used providing moderate enantioselectivity (72% and 56%, respectively) and excellent diastereoselectivity when employing cinnamyl bromide (>95/5 anti/syn). However, the distereoselectivity when using crotyl bromide was poor and other functionalized allyl bromides under our method afforded low enantioselectivities for the alcohol products. In these types of indium-mediated additions, solvent plays a major role in determining the nature of the organoindium intermediate and we observed the susceptibility of some allylindium intermediates to hydrolysis in protic solvents. Under our reaction conditions using a polar aprotic solvent, we suggest that an allylindium(III) species is the active allylating intermediate. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.

Exploring the use of APTS as a fluorescent reporter dye for continuous glucose sensing.

The anionic fluorescent dye, aminopyrene trisulfonic acid (APTS), was synthesized and used in a solution-based two-component glucose-sensing system comprising the dye and a boronic acid-appended viologen. The fluorescence of the dye was quenched in the presence of the viologen and the fluorescence restored upon glucose addition. An important feature of this fluorophore is that it can be covalently bonded to a polymer through the amine group without a significant effect on optical properties. Two APTS derivatives, functionalized with polymerizable groups, were synthesized and immobilized in hydroxyethyl methacrylate (HEMA)-based hydrogels. The latter were used to continuously monitor glucose. The fluorescence signal modulation, signal stability, reversibility, reproducibility, and pH sensitivity of the hydrogels were evaluated. The APTS dyes described herein are insensitive to pH changes within the physiological range, both in solution and when immobilized in a hydrogel. When APTS is used in conjunction with boronic acid-appended viologens to sense glucose, the system displays some pH sensitivity because of the presence of the boronic acid.

Boronic acid-based bipyridinium salts as tunable receptors for monosaccharides and alpha-hydroxycarboxylates.

Several novel diboronic acid-substituted bipyridinium salts were prepared and, using a fluorescent reporter dye, were tested for their ability to selectively bind various monosaccharides and alpha-hydroxycarboxylates in an aqueous medium. The fluorescence sensing mechanism relies on the formation of a ground-state charge-transfer complex between the dye and bipyridinium. An X-ray crystal structure of this complex is described herein. Glucose selectivity over fructose and galactose was achieved by designing the bipyridinium-based receptors to be capable of attaining a 1:1 receptor/substrate stoichiometry via cooperative diboronic acid binding.