UC Santa Cruz
OBSERVATIONS IN REACTIVITY BETWEEN BH CONTAINING COMPOUNDS AND ORGANOMETALLIC REAGENTS: SYNTHESIS OF BORONIC ACIDS, BORONIC ESTERS, AND MAGNESIUM HYDRIDES
- Author(s): Clary, Jacob William
- Advisor(s): Singaram, Bakthan
- et al.
Diisopropylaminoborane (BH2-N(iPr)2) is prepared by reacting lithium diisopropylaminoborohydride (iPr-LAB) with trimethylsilyl chloride (TMSCl). Aliphatic, aromatic, and heteroaromatic (diisopropylamino)boranes are readily synthesized at ambient temperature (0 °C) in 1h by the reaction of Grignard reagents with (BH2-N(iPr)2). Two contending reaction pathways have tentatively been identified. In one pathway, bromomagnesium hydride (HMgBr) acts as the leaving group from the initially formed bromomagnesium organo(diisopropylamino)borohydride, affording the product organodiisopropylaminoborane (RBH-N(iPr)2). The increased sterics and the diminished Lewis acidity of (RBH-N(iPr)2) prevents it from further reacting with Grignard reagents. In the second pathway, the product may be formed by a hydride transfer from bromomagnesium organo(diisopropylamino)borohydride to the starting material (BH2-N(iPr)2). It was found that only 1.2 equivalents of (BH2-N(iPr)2) was required for greater than 95% conversion to the organo(diisopropylamino)borane. During the mechanistic investigation, bromomagnesium diisopropylaminoborohydride was identified as a byproduct and was subsequently synthesized from diisopropylamine borane and methylmagnisum chloride. This borylation reaction can be carried out under Barbier conditions, where (BH2-N(iPr)2) traps the in situ formed Grignard reagent from the corresponding organic halide and magnesium metal. Simple acid hydrolysis of the product organo(diisopropylamino)borane leads to the corresponding boronic acid in good to excellent yield.
Grignard reagents (aliphatic, aromatic, heteroaromatic, vinyl or allylic) react with one equivalent of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane, (pinacolborane, PinBH) at ambient temperature in tetrahydrofuran (THF) to afford the corresponding pinacol boronates. Initially formed dialkoxy alkylborohydride intermediate quickly eliminates hydridomagnesium bromide (HMgBr) and affords the product boronic ester in very good yield. Hydridomagnesium bromide (HMgBr), in turn disproportionates to a 1:1 mixture of magnesium hydride (MgH2) and magnesium bromide (MgBr2) on addition of pentane to the reaction mixture. DFT calculations (Gaussian09) at the B3LYP/6-31G(d) level of theory show that disproportionation of HMgBr to MgH2 and MgBr2 is viable in the coordinating ethereal solvents. This reaction also can be carried out under Barbier conditions where the neat PinBH is added to the flask prior to the in situ formation of Grignard reagent from the corresponding organic halide and magnesium metal. Pinacol boronic ester synthesis under Barbier conditions does not give Wurtz coupling side products from reactive halides, such as benzylic and allylic halides. The reaction between PinBH and various Grignard reagents is an efficient, mild and general method for the synthesis of pinacol boronates.