Gary B. Fisher

Synthesis and characterization of lithium aminoborohydrides: A new class of powerful reducing agents

Abstract Lithium aminoborohydrides (LiABH 3 ), obtained by the reaction of n-BuLi with amine-boranes, are powerful reducing agents, comparable to lithium aluminum hydride, yet selective in their reducing properties. LiABH 3 s reduce esters, lactones, and anhydrides to the corresponding alcohols, while carboxylic acids are not reduced. Test reductions show that LiABH 3 s also reduce a wide range of functional groups, including amides, epoxides, oximes, nitriles, and halides.

Lithium aminoborohydrides 16. Synthesis and reactions of monomeric and dimeric aminoboranes.

Aminoboranes are synthesized in situ from the reaction of the corresponding lithium aminoborohydrides (LABs) with methyl iodide, trimethylsilylchloride (TMS-Cl), or benzyl chloride under ambient conditions. In hexanes, the reaction using methyl iodide produces aminoborane and methane, whereas in tetrahydro-furan (THF) this reaction produces amine-boranes (R1R2HN:BH3) as the major product. The reaction of iPr-LAB with TMS-Cl or benzyl chloride yields exclusively diisopropylaminoborane [BH2-N(iPr)2] in THF as well as in hexanes at 25 degrees C. Diisopropylaminoborane and dicyclohexylaminoborane exist as monomers due to the steric requirement of the alkyl group. All other aminoboranes studied are not sterically hindered enough to be monomers in solution, but instead exist as a mixture of monomers and dimers. The dimers are four-membered rings formed through boron-nitrogen coordination. In general aminoboranes are not hydroborating reagents. However, monomeric aminoboranes, such as BH2-N(iPr)2, can reduce nitriles in the presence of catalytic amounts of LiBH4. This BH2-N(iPr)2/LiBH4 reducing system also re-duces ketones, aldehydes, and esters. Diisopropylaminoborane, synthesized from iPr-LAB, can be converted into boronic acids by a palladium-catalyzed reaction with aryl bromides. Aminoboranes derived from heterocyclic amines, such as pyrrole, pyrazole, and imidazole, can be prepared by the direct reaction of borane/tetrahydrofuran (BH3:THF) with these heterocyclic amines. It has been reported that pyrazole-derived aminoborane forms a six-membered dimer through boron-nitrogen coordination, where as, pyrrolylborane forms a dimer through boron-hydrogen coordination. Pyrrolylborane monohydroborates both alkenes and alkynes at ambient temperatures. Hydroboration of styrene with pyrrolylborane followed by hydrolysis gives the corresponding boronic acid, 2-phenylethylboronic acid, in 40% yield. Similarly phenylacetylene is mono-hydroborated by pyrrolylborane, to give E-2-phenylethenylboronic acid in 50% yield.

Aminoborohydrides. 8. A facile reduction of aliphatic and benzylic azides to the corresponding amines in high yield and purity using lithium N,N-dimethylaminoborohydride

Abstract Lithium N,N-dimethylaminoborohydride (LiMe2NBH3) reduced both 3α-azidocholest-5-ene and 3β-azidocholest-5-ene in air to give the corresponding 3α-aminocholest-5-ene and 3β-aminocholest-5-ene in 98% isolated yields. Aliphatic and benzylic azides were also reduced with LiMe2NBH3 to give the corresponding amines in isolated yields ranging from 85 to 98%. The reductions were complete in 1–3 hours and required only a simple acid-base extraction to isolate the desired amines.

Aminoborohydrides. 3. A facile reduction of tertiary amides to the corresponding amines and alcohols in high purity using lithium aminoborohydrides. Sterically controlled selective CN or CO bond cleavage

Abstract Lithium aminoborohydrides (LiABH 3 ), obtained by the reaction of n-BuLi with amine-boranes, are powerful reducing agents for the reduction of tertiary amides to the corresponding amines or alcohols. Lithium pyrrolidinoborohydride (LiPyrrBH 3 ) and lithium diisopropylaminoborohydride (LiH 3 BN(i-Pr) 2 ) reduce both aliphatic and aromatic tertiary amides to give either the corresponding alcohol or amine, depending on the steric requirement of the tertiary amide and the LiABH 3 used. The yields of amines and alcohols from this procedure range from very good to essentially quantitative.

Boranes in synthesis. 2. Asymmetric synthesis of β-amino alcohols. A facile conversion of 2-amino acetophenones to the corresponding β-amino alcohols in high enantiomeric purity

The asymmetric reduction of 2-amino acetophenones with Ipc2BH or Ipc2BCl at −78°C, yields the corresponding β-amino alcohols in good to excellent yields. Although only modest (12–45% ee) enantiomeric excesses were obtained with Ipc2BH, 75–99% enantiomeric excesses were obtained when Ipc2BCl was used as the asymmetric reducing agent.

Aminoborohydrides. 9. Selective reductions of aldehydes, ketones, esters, and epoxides in the presence of a nitrile using Lithium N,N-dialkylaminoborohydrides

Abstract A series of competitive reductions of several functional groups was carried out in the presence of aromatic and aliphatic nitriles using Lithium N,N-dimethylaminoborohydride (LiMe 2 NBH 3 ) or Lithium Pyrrolidinoborohydride (LiPyrrBH 3 ) as the reducing agents. Both LiMe 2 NBH 3 and LiPyrrBH 3 cleanly and quantitatively reduced aldehydes, ketones, esters, and epoxides in the presence of the nitriles to give the corresponding reduction products in yields ranging from 85 to 98%. In no case was the nitrile reduced: no products arising from the reduction of nitriles were detected by GC analysis. Two difunctional nitriles were also reduced to give complete reduction of the more active functional group with no reduction of the nitrile.

A Facile New Synthesis of Aldehyde Enamines in High Yield and High Purity

Abstract Aldehyde enamines were synthesized in excellent yield and purity by reacting an aldehyde with 2 equivalents of a secondary amine in cyclohexane in the presence of 1.5 equivalents of CaH2. Distilled yields ranged from 65%-92%.

Boranes in synthesis. 3. Conversion of the morpholine and pyrrolidine enamines of symmetrical dialkylketones to the corresponding threo-β-amino alcohols via hydroboration/oxidation

Abstract The hydroboration of the morpholine and pyrrolidine enamines of symmetrical dialkylketones with BMS followed by methanolysis and oxidation with basic hydrogen peroxide gave the corresponding threo-β-amino alcohols in moderate yields.