Aminoborohydrides. 6. Diastereoselective reduction of the carbon-nitrogen double bond in chiral imines using lithium diethylaminoborohydride and lithium diisopropylaminoborohydride
✍ Scribed by Joseph C. Fuller; Christopher M. Belisle; Christian T. Goralski; Bakthan Singaram
- Book ID
- 104214725
- Publisher
- Elsevier Science
- Year
- 1994
- Tongue
- French
- Weight
- 312 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
Lithium aminoborohydrides (LAB). obtained by the reaction of n-B&i with amine-boranes, readily reduce imines to the correspovldng second&-y amines. Lithium diethyiaminoborohydride [Li(Et)zNBHj] and
lithium diisopmpyianmw~~dride [Li(i-Pr)flBHJ] reduce chiral aliphatic and aromatic hnines, dprivedfrom a-methylbenzylumines, to give the corresponding enantiomerically enriched secondary amines. The yielak of secondary amines from this procedure range from very good w essentially quantitative. The diastereomeric inakion in the reduction of the carbon-nitrogen double bond with Li(Et)zNBHj and Li(i-Pr)2NBH3 ranged from moderate to very good The reduction of imines is very important in organic chemistry2 and has been stwJied intensively, especkdly in connection with the syntheses of alkaloids3 and amino acids4 The use of chiral amines as chiral auxiliarie&7 and chiral building blocks* has extensive applications in modem synthetic chemistry. The most common procedure for the synthesis of chiral amines involves the hydrogenation of prochiral schiff bases." While this method requires the use of a separate chiral auxiharypC the mom s nccessfnl route has been to hydrogenate or reduce chiral imines synthesized from the corresponding prochiral ketone and a chirrd amine.to However, these methods suffer from the need of having to use a large excess of hydride, high temperatures over extended periods of time, and the need to rigorously exclude air and water during the reduction. 9e-f Alternatively, enantiomericaJly pure primary and secondary amines can be synthesized from chiral organoboranes. 11 Herein, we report the synthesis of enantiomericaJly enriched secondary amines via the reduction of chiral imines with Iithinm aminoborohydrides (LAB) to give asymmetric induction as high as 92%. Recently,lZ we disclosed a new class of reducing agents now known as LAB reagents, comparable in reduction potential to lithium aluminum hydride. LAB reagents arc stable to air, are non-pyrophoric, and are thermally stable. LAB reagents can be prepared readily in large scale and in essentially quantitative yield from n-BuLi and any amine-borane complex.12 We were interested in reducing the imines derived from (s)_(-)-a-methylbenzylamine and ketones, such as 2octanone, pinacolone, cyclohexanone, acetophenone. 2'-acetonapthone and 2-acetylpyridii. These chhal imines were synthesized by the reported procednm tot and purified by distiRation prior to reduction with LAB. The reductions were carried out by mixing the reactants at 0 "c for 1 h under nitrogen, followed by quenching at 0 T. Our results are summarized in Table 1, and only the major diastereomers are shown. The reduction of chh-al imines with either lithium diethylaminoborohyd [Li(Et)@BHs] or lithium diisopropylaminoborohyfide &i(i-Pr)2NBH3] to the corresponding enantiomerically enriched secondary amines is quite general.l3 Additionally. Li(Et)zNBH3 efficiently reduced the imine derived from pinacolone and (S)-(-)-a-methylbenzylamine. to the corresponding optically active secondary amine in 92 46 de (eq. 1).