Preparative Biorganic Chemistry Part 10 Asymmetric Reduction of Bicyclo[2.2.2]Octane-2,6-Diones with Baker's Yeast

Asymmetric Reduction of Ketones with Catecholborane Using 2,6-BODOL Complexes of Titanium(IV) as Catalysts

“…[11] However, since we found that the compound was acid sensitive we give here the NMR data in benzene solution: 1 (AE)-endo-6-Hydroxy-bicyclo[2.2.2]octane-2-one: The synthetic sequence was adopted from the literature. [29] The first step, the synthesis of 3-allyl cyclohexanone, was performed according to the literature [30] from 2-cyclohexenone (3.0 g, 31 mmol), TiCl 4 (3.7 mL, 33 mmol), and allyltrimethylsilane (5.0 mL, 32 mmol), with the exception that after the addition of water (200 mL) the mixture was filtered through Celite to remove the thick precipitate of titanium oxide. In the second step, the crude product from above (4 g) was diluted with MeOH (100 mL) and cooled to À 76 8C, and O 3 was bubbled through the stirred solution until it turned blue-violet.…”

Bicyclo[2.2.2]octane-derived chiral ligands—synthesis and application of BODOLs in the asymmetric reduction of acetophenone with catecholborane

“…In the new protocol, BODOLs 3a-l were synthesized by the addition of the corresponding Grignard reagent to hydroxyketone 1 [25][26][27] in ether solution without prior protection ( Table 1). The reaction was performed at 25°C using the organomagnesium In the synthesis of the substituted BODOLs, 1 equiv of the reagent was added upon which a precipitate was formed, which dissolved after the addition of another 1.5 equiv.…”

Asymmetric baker’s yeast reductions of bridgehead-substituted bicyclo[2.2.2]octane-2,6-dione derivatives followed by conversion into catalytically active BODOLs for the diethylzinc addition to benzaldehyde

“…Inspired by this and the continuous need for novel chiral building blocks led us to examine 9 as a substrate for asymmetric reduction with baker's yeast. To the best of our knowledge, 4-substituted bicyclo [2.2.2]octanes-2,6-diones apart from 2 29 have not been investigated as substrates for baker's yeast reduction.…”

“…27,28 Moreover, they have served well as substrates in biotransformations resulting in optically active compounds, pioneered by Mori et al who in 1990 reported the highly enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione derivatives 1-4 using baker's yeast (Scheme 1). 29,30 Several examples exist where optically active hydroxy bicyclo [2.2.2]octanones serve as important chiral building blocks in the synthesis of bioactive natural products. 9,[31][32][33] The development of bicyclo [2.2.2]octane derivatives, to be used as ligands 17,18,20,23,24,[34][35][36][37][38] and scaffolds in natural product mimetics, 39,40 is an ongoing project in our laboratories.…”