9-O-(1,2;5,6-Di-O-isopropylidene-a-D-glucofuranosyl)-9-boratabicyclo[3.3.1]nonane, Potassium Salt

[101696-41-7]  · C20H34BKO6  · 9-O-(1,2;5,6-Di-O-isopropylidene-a-D-glucofuranosyl)-9-boratabicyclo[3.3.1]nonane, Potassium Salt  · (MW 420.40)

(chiral borohydride reagent for enantioselective reduction of ketones1)

Alternate Names: K-glucoride; K 9-O-DIPGF-9-BBNH.

Solubility: usually prepared and stored in THF solution.1

Analysis of Reagent Purity: 11B NMR (d 1.33, br s) and strong absorption at 2038 cm-1 in the IR spectrum (B-H str); stoichiometric ratio of K:B:H as 1:1:1 by analysis.1

Preparative Method: 9-BBN, by reaction with the chiral alcohol 1,2;5,6-di-O-isopropylidene-a-D-glucofuranose (DPGF) (both commercially available), is transformed into the borinic ester 9-O-DIPGF-9-BBN which, by treatment with a modest excess (1.1-1.5 equiv) of potassium hydride, is completely transformed within 2 h into K-glucoride.1

Handling, Storage, and Precautions: K-glucoride is relatively stable toward disproportionation at rt, especially when the THF solution is stored over excess potassium hydride under a positive pressure of nitrogen.1

Enantioselective and Diastereoselective Reduction of Carbonyl Compounds.

K-Glucoride is the first example of a well-defined chiral borohydride reagent containing a monosaccharide as chiral auxiliary;2 moreover, it has only one hydride per reagent molecule.1a K-Glucoride allows the reduction of various ketones1a-c to the corresponding alcohols in THF, even at -78 °C; it was first used for hindered alkyl phenyl ketones (like pivalophenone)1a and it gave considerably higher enantioselectivity than Noyori's BINAL-H reagent (see Lithium Aluminum Hydride-2,2-Dihydroxy-1,1-binaphthyl).1a Reduction of unhindered aliphatic ketones (like 2-butanone) with the same reagent gave only very low optical yields; for such compounds the lithium hydrido-9-BBN-nopol benzyl ether adduct (NB-Enantride™)1a is much more favorable. On the other hand, the reduction of pinacolone, which is relatively hindered, gave a reasonable enantioselectivity (70%), while NB-Enantride gave only 2%. A significant effect of reaction temperature on optical induction was demonstrated for propiophenone,1c with ee's varying from 92% at -78 °C to 76% at 0 °C. It is noteworthy that the alcohols obtained were always enriched in the (R) enantiomer.

Prochiral ketones bearing various functionalities near the carbonyl group can be reduced by K-glucoride; for example very good optical yields can be obtained in the reduction of a-keto esters3a to the corresponding a-hydroxy esters. The ee's obtained are always close to 100%, even with relatively hindered derivatives. Moreover, all of the a-hydroxy esters obtained were enriched in the (S) enantiomer. In contrast, B-isopinocampheyl-9-borabicyclo[3.3.1]nonane (Alpine-borane®)3a usually gave lower optical yields and very slow reactions with relatively hindered compounds; in this case the absolute configuration of product depends on the starting a-keto ester. While a-hydroxy esters can be obtained with high ee by reduction with K-glucoride, the same procedure gave only poor results in the asymmetric reduction of b-keto esters.3a

Secondary or tertiary b-amino alcohols can be obtained by reduction of a-amino ketones with K-glucoride;3b best results were obtained starting from aromatic a-amino ketones (44-73% ee), while aliphatic amino ketones gave only low enantioselectivity (9-33% ee). Interestingly, the amino alcohols obtained are enriched in the (S) enantiomer and the enantioselectivity increases with the bulkiness of the substituents on the amino group.

a,b-Alkynic ketones can be reduced to the corresponding (R)-alkanols with K-glucoride;3c ee's are good with compounds bearing an internal triple bond (61-87%), while they drop with terminal alkynes (in this case the (S) configuration is preferred). K-glucoride can also be used for the diastereoselective reduction of chiral racemic cyclic and bicyclic ketones to give the less stable alcohol with excellent diastereoselectivity.1c

Other Reductions.

There is an example of a reduction (resolution) of racemic 1,2-epoxyalkanes to give the corresponding (R)-2-alkanols with moderate ee (up to 43.3%).4

The enantioselective synthesis of optically active secondary amines via asymmetric reduction of prochiral ketimines was studied by screening various chiral hydrides.5a,b In this case, K-glucoride gave only disappointing results and was inferior to other reagents. Better results were obtained in the asymmetric reduction of prochiral N-diphenylphosphinylimines to chiral N-(diphenylphosphinyl)amines (eq 1),5c which can then be readily converted into optically active primary amines. For this reaction the stereochemical course depends dramatically on the relative bulkiness of the groups R1 and R2. The reaction conditions for reduction of C=N double bonds are the same as used for ketones, but the high reactivity of diphenylphosphinylimines dramatically reduces the reaction time.

Finally, K-glucoride can also be used for the enantioselective reduction with moderate ee (52%) of 1-substituted 2-methylisoquinolinium salts, which are employed in the preparation of 1-substituted 2-methyltetrahydroisoquinoline alkaloids.5d

1. (a) Brown, H. C.; Park, W. S.; Cho, B. T. JOC 1986, 51, 1934. (b) Brown, H. C.; Park, W. S.; Cho, B. T.; Ramachandran, P. V. JOC 1987, 52, 5406. (c) Brown, H. C.; Cho, B. T.; Park, W. S. JOC 1988, 53, 1231.
2. Kunz, H.; Rück, K. AG(E) 1993, 32, 336.
3. (a) Brown, H. C.; Cho, B. T.; Park, W. S. JOC 1986, 51, 3396. (b) Cho, B. T.; Chun, Y. S. TA 1992, 3, 341; (c) Cho, B. T.; Park, W. S. Bull. Korean Chem. Soc. 1987, 8, 257.
4. Cha, J. S.; Lee, K. W.; Yoon, M. S.; Lee, J. C.; Yoon, N. M. H 1988, 27, 1713.
5. (a) Cho, B. T.; Chun, Y. S. TA 1992, 3, 1583. (b) Cho, B. T.; Chun, Y. S. TA 1992, 3, 337. (c) Hutchins, R. O.; Abdel-Magid, A.; Stercho, Y. P.; Wambsgans, A. JOC 1987, 52, 702. (d) Cho, B. T.; Han, C. K. Bull. Korean Chem. Soc. 1991, 12, 565.

Luca Banfi, Enrica Narisano, & Renata Riva

Università di Genova, Italy

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