Eapine-Borane

The enantioselective reduction of 3-butyn-2-one (7) is achieved in 82 % ee by use of the Eapine-Borane 22.9 Application of the commercial available Alpine Borane leads to a lower enantio-selectivity (77 % ee). The mechanism of this reduction is explained in Chapter 13. 

Brown and coworkers [1] have found that NB-Enantrane is effective only for the reduction of a,(3-acetylenic ketones. The reduction of other ketones is too slow to be of any practical use. The retarded rate is attributed to the steric bulk at the 2 position since no internal coordination has been detected by "B NMR (6 86 ppm) [2]. On the other hand, Alpine-Borane has proven to be versatile reagent for the asymmetric reduction of variety of ketones. Consequently, two reagents B-(iso-2-ethylapopinocampheyl)-9-borabicyclo[3.3.1]nonane (Eapine-Borane) and B-(iso-2- -propylapopinocampheyl)-9-BBN (Prapine-Borane) having increasing steric requirement at the 2 position, are prepared by the hydroboration [3] of 2-ethyl- and 2-n-propylapopinene. 

The reagent Eapine-Borane, prepared (Eq. 26.15) from (-)-2-ethylapopinene by hydroboration with 9-BBN have been studied for its reaction with representative ketones and is found to react at faster rate than NB-Enantrane, but at slightly slower rate than Alpine-Borane (Table 26.15) [1]. 

Table 26.15 Reaction of Eapine-Borane with representative ketones at 25 °C [ 1 ]...

The high asymmetric induction achieved with Eapine-Borane for the a,p-acetylenic ketones and a-ketoesters led an examination of the reduction of a series of a,p-acetylenic ketones (Eq. 26.16) and a-ketoesters (Eq. 26.17), and the comparative reduction data of Eapine-Borane with Alpine-Borane are summarized in Tables 26.16 and 26.17. It should be mentioned that Eapine-Borane offers no advantage for the reduction of aromatic a-ketoesters. Thus, Eapine-Borane is an efficient reagent for the chiral reduction of a,(3-acetylenic ketones (Table 26.16) [1] and of alkyl a-ketoesters (Table 26.17) [1], of appreciable steric difference between the two groups on both sides of the carbonyl group. 

Prapine-Borane is prepared neat from (-)-2- -propylapopinene by hydrobo-ration with solid 9-BBN, using the same procedure as used for the preparation of Alpine-Borane and Eapine-Borane. (-)-2- -Propylapopinene is prepared in 84% yield from nopyltosylate by treatment with dimethylcuparate, prepared in situ [5] from methyllithium and cuprous iodide (Scheme 26.4). 

The rate of reduction of representative a,(3-acetylenic ketones with Prapine-Borane is slightly slower than Eapine-Borane but with improved chiral induction (Eq. 26.18 Table 26.18) [1]. 

Ketone Reagent equiv Reaction time (h) With Prapine-Borane With Eapine-Borane With Alpine-Borane... 

However, unlike Eapine-Borane and Alpine-Borane Prapine-Borane fails to provide improved asymmetric induction in the reduction of a-keto esters (Table 26.19) [1]. 

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