Lithium aminoborohydride

Lithium aminoborohydrides, which are readily obtained by reaction of n-BuLi with amine-boranes327,328, are excellent reagents for the reduction of imines to their corresponding secondary amines (equation 80)329. If the substrate possesses chirality, then there is considerable diastereoselectivity in this reaction (up to 90%). 

A review describing the major advances in the field of asymmetric reduction of achiral ketones using borohydrides, exemplified by oxazaborolidines and /9-chlorodiisopino- camphenylborane, has appeared. Use of sodium borohydride in combination with chiral Lewis acids has been discussed.298 The usefulness of sodium triacetoxyboro-hydride in the reductive amination of aldehydes and ketones has been reviewed. The wide scope of the reagent, its diverse and numerous applications, and high tolerance for many functional groups have been discussed.299 The preparation, properties, and synthetic application of lithium aminoborohydrides (LABs) have been reviewed. 

Fluoropyridines undergo amination in good yield on treatment with lithium aminoborohydride reagents in THF at 65 °C <2003OL3867>. As an example, reaction with 1.1 equiv of lithium piperidinyl borohydride in THF at 65 °C gives 2-piperidinylpyridine in 99% yield (Equation 104). 2-Chloropyridine can also be used as a substrate in the presence of excess borohydride. 

Lithium aminoborohydride has proven to be a mild reagent to generate 2-dialkylaminopyridines from 2-fluoropyridine. This reaction is generally applicable to the introduction of unhindered secondary amines <03OL3867>. 

Lithium aminoborohydrides are obtained by the reaction of -BuLi with amine-boranes [FF2, FH5, NT2]. They can be generated in situ as THF solutions or as solids when formed in diethylether or hexane (n-BuLi must then be used in sub-stoichiometric amounts). They are stable under dry air and are slowly decomposed by water [NT2] or methanol so that workup of the reactions mixtures can be carried out with 3M HCl. They reduce alkyl halides (Section 2.1), epoxides (Section 2.3), aldehydes, and ketones (Section 3.2.1) (in the latter case with an interesting stereoselectivity [HFl]), and esters to primary alcohols (Section 3.2.5). a,(3-Unsaturated aldehydes, ketones, and esters are reduced to allyl alcohols (Section 3.2.9) [FF2, FS2]. Depending on the bulkiness of the amines associated with the reagent and to the substrate, tertiary amides give amines or alcohols (Section 3.2.8) [FFl, FF2]. Amines are also formed from imines (Section 3.3.1) [FB1 ] and from azides (Section 5.2) [AFl]. However, carboxylic acids remain untouched. 

These can be easily prepared by reaction of di- or trialkylboranes with lithium aminoborohydrides [HAl], The properties of two types of reagents have been explored Li(n-Bu)BH3 [KM2] and the boratabicyclononane Li 9-BBN-H 1.3 (on page 11) [BMl, KBIJ. No special features have been pointed out in relation to other reducing agents. 

Lithium aminoborohydrides.1 The reagent 1 is a typical member of a number of lithium aminoborohydrides, prepared by reaction of BuLi with amine borancs in quantitative yields. These reagents can be stored at 25" under N2 for at least six months they are not pyrophoric. They are comparable to LiAIH4 as rcductants. Thus 1 reduces carbonyl compounds (including esters) in high yield. lactones and anhydrides are reduced, but carboxylic acids are not reduced. In addition 1 reduces amides, epoxides, oximes, nitriles, and even halides. 

Lithium aminoborohydrides in reduction of N-alkyllactams and synthesis of 2-dialkylaminopyridines 05AA61. 

Lithium Aminoborohydrides Reagents with Multiple Personalities... 

This chapter describes newly discovered reactions and synthetic utilities of lithium aminoborohydrides (LABs) including (1) the reduction of nitriles to amines, (2) the direct synthesis of amine-borane complexes from LABs and benzylic or alkyl halides (nitrogen transfer), and (3) the tandem nitrogen transfer/reduction of halogen-substituted benzonit-riles to give the corresponding aminobenzylamines. 

Several years ago, we reported the synthesis and synthetic utility of lithium aminoborohydrides (LABs) a new class of powerful, safe, and highly selective reducing agents (2, 3). These reagents performed many of the transformations for which lithium aluminum hydride is usually used. Thus, the following reduction reactions were carried out with LABs aldehydes and ketones to alcohols, esters to alcohols, oc,P>unsaturated ketones to allylic alcohols, a,P-unsaturated esters to allylic alcohols, alkyl halides to hydro-carbons, azides to amines, and epoxides to alcohols. These reduction reactions are summarized in Figure 3. 

Figure i. Summary of the reduction reactions of lithium aminoborohydrides, (Reproducedfrom reference 2. Copyright 1994 American Chemical Society,)... 

In the last entry of Table I, it is noted that the reduction had to be done with lithium aminoborohydride (LiH3BNH2). Myers further expanded the utility of this reagent with additional examples of the reduction of alkylated pseudoephedrine amides to chiral alcohols of high ee (Table II), and the reduction of iV,iV-disubstituted dodecanecarboxamides and 1-adamantanecarbox-amides to the corresponding alcohols, respectively (Table III) (5). 

Table III. Reduction of Amides with Lithium Aminoborohydride...

Since the initial discovery of lithium aminoborohydrides (LABs) in 1994, these reagents have found increasing use in organic synthesis. With the discovery of the broader personalities of these reagents described in this paper, we have opened a whole new frontier of LAB chemistry which is only beginning to be explored. 

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