2- Octanone reduction

Hydrophobic ILs have been considered as a solvent for biocatalytic reactions. It was shown that the reaction of 2-octanone reduction to 2-octanol catalysed by alcohol dehydrogenase is faster when IL BMIM (Cp3S02)2N is present in comparison to organic solvent applied so far (Eckstein et al., 2004). Additional beneficial effects of ILs is reduction of the toxicity towards the cell and possibility of their application in whole-cell biocatalysis (Weuster-Botz, 2007 Pfruender et al,. 2004). This advantageous effect comes from excellent solvent properties of ILs extracting either products or reaction substrates. 

Octonol is an intermediate for the production of several optically active pharmaceuticals, such as steroids and vitamins. The asymmetric reduction of 2-octanone to (5)-2-octonol by baker s yeast was inhibited severely by substrate and product concentration of 10 him and 6 mM respectively. Whole-cell biotransformation of 2-octanone in a water-ra-dodecane biphasic system yielded a high product concentration of 106him with 89% ee in 96h [37],... 

Li, Y.-N., Shi, X.-A., Zong, M.-H. et al. (2007) Asymmetric reduction of 2-octanone in water/organic solvent biphasic system with baker s yeast FD-12. Enzyme and Microbial Technology, 40, 1305-1311. 

BINAL-H reagents 45 are not effective in the enantioselective reduction of dialkyl ketones.53 For example, reaction of benzyl methyl ketone with (S)-45 gives (S )-l-phenyl-2-propanol in only 13% ee (71% yield). Reaction of 2-octanone with (R)-45 produces (S )-2-octanol in 24% ee (67% yield).53 This drop of ee values in the reaction may be explained by the lower energy difference between the favored transition state 48 and unfavored transition state 49 caused by the lack of the above-mentioned n-n repulsion between the reductant and the substrate dialkyl ketone. 

In the asymmetric reduction of ketones, stereodifferentiation has been explained in terms of the steric recognition of two substituents on the prochiral carbon by chirally modified reducing agents40. Enantiomeric excesses for the reduction of dialkyl ketones, therefore, are low because of the little differences in the bulkiness of the two alkyl groups40. In the reduction of ketoxime ethers, however, the prochiral carbon atom does not play a central role for the stereoselectivity, and dialkyl ketoxime ethers are reduced in the same enantiomeric excess as are aryl alkyl ketoxime ethers. Reduction of the oxime benzyl ethers of (E)- and (Z)-2-octanone with borane in THF and the chiral auxiliary (1 R,2S) 26 gave (S)- and (R)-2-aminooctane in 80 and 79% ee, respectively39. 

Thienothiophenes, like thiophenes and benzo[h]thiophenes, easily undergo reductive desulfurization with Raney nickel. The method was fvst applied in this series by Challenger et to determine the structures of 2-acetylthieno[3,2-h]thiophene and 2-acetylthieno[2,3-hl-thiophene the former gave 2-octanone (229), and the latter 5-methyl-heptan-2-ol (230) [Eqs. (75) and (76)]. 

Enantioselective reduction of simple aliphatic ketones is one of the most challenging of the currently unresolved problems in this field. The Rh/4 complex catalyzed the hydrosilylation of 2-butanone with diphenylsilane at 0 °C, which after hydrolysis gave (S)-2-butanol in 56% ee (Scheme 3) [17]. 2-Octanone and 4-phenyl-2-butanone were reduced with diphenylsilane in the presence of the cationic Rh/EtTRAP-H at -50 °C and gave optical yields of 77% and 81%, respectively [12], The cationic Rh/(R,R)-t-Bu-MiniPHOS was also effective for the reduction of 4-phenyl-2-butanone with 1-naphthylphenylsilane at -20 °C, affording the R product in 80% ee [13]. 3-Methyl-2-butanone was reduced using the Rh/4 complex with 76% optical yield [17]. Hydrosilylation of cyclohexyl methyl ketone with the Rh/(R,S)-2 complex followed by hydrolysis afforded the R alcohol in 87% ee [8]. Highly enantioselective hydrosilylation of pinacolone with diphenylsilane at -20 °C was achieved by means of the Rh/4 complex and yielded the desired R product in 95% ee [17]. 

Alkyl aryl ketimines were reduced with up to 99% ee (Scheme 8) [24]. The high enantioselectivity was not affected by the E Z ratio of the imines. For example, a 1.8 1 E Z mixture of the N-propylimine of 4 -methoxy-3-methyIbuty-rophenone was converted to the desired product in 97% optical yield. Hydrosilylation of the N-propylimine of cyclohexyl methyl ketone with a substrate to Ti molar ratio of 2,000 1 was completed to give the product in 98% ee [24]. N-Benzylimine of 2-octanone, a simple aliphatic ketimine, was reduced with 69% optical yield. The reduction of W-benzyl-l-indanimine gave the corresponding amine in 92% ee (Scheme 9) [24]. 

Asymmetric reduction of prochiral ketones. Chiral metal hydrides previously investigated have been effective only for asymmetric reduction of aromatic or a,p-ucclylenic ketones. This new reagent unexpectedly reduces straight-chain aliphatic ketones such as 2-bulanonc and 2-octanone to the corresponding (S)-alcohols in 76%... 

Yadav, S., Banerjee, S., Maji, D., and Lahiri, S. (2007) Synthesis ofbicyclo[3.2.1] octanones via ketyl radical promoted rearrangements under reductive PET... 

Ti complexes prepared from Ti[OCH(CH3)2]4 and one equivalent of chiral diol catalyzed the reduction of ketones with catecholborane [44], Scheme 5 shows a recent example utilizing anisyl-BODOL (7) as a chiral auxiliary [45], Several aromatic ketones and 2-acetylcyclohexanone were reduced with an optical yield of up to 98%. Reduction of 2-octanone, a simple aliphatic ketone, gave the corresponding alcohol in 87% ee. 

In addition to this, that an interesting novel emulsion membrane reactor concept overcomes the difficulties of the large solvent volume otherwise required for the reduction of poorly soluble ketones [30]. 2-Octanone was reduced by a carbonyl reductase from Candida parapsilosis to (S)-2-octanol with > 99.5 % ee and total turnover number of 124 - the 9-fold value of that obtained in a classical enzyme reactor. 

Chiral 4-substituted Pybox derivatives (1) were synthesized as chiral adjuvants to study remote electronic effects of the substituents in the asymmetric hydrosilylation. The 4-Cl-Pybox-(5,5)-ip-Rh catalyst afforded the highest result (80% ee (5)) for the reduction of 2-octanone to 2-octanol in 88% yield. 

Recently, the preparation of the chiral biphenyl (6) and its use as a modifying agent with LAH has been reported." A complex of LAH-(6)-EtOH (1 1 1) at —78°C gives the best enantiose-lectivities in the reduction of prochiral ketones. Similar to Noyori s reagent, use of the LAH complex with (S)-(6) leads to the (S)-alcohol. Enantioselectivity is usually high for aromatic ketones (acetophenone 97% ee, 93% yield). This reagent reduces 2-octanone in higher enantioselectivity (76% ee) than 3-heptanone (36% ee). 

Alcohols 3-8, obtained by the reduction of the corresponding ketones with equimolar amounts of BMS and are obtained with high ees (ee values given are obtained using 0.1 equiv of (R)-1). Enantioselectivity is excellent (often similar or only slightly lower than those reported in the CBS reduction) for aromatic and hindered methyl ketones, (e.g. 3-5) and is also good for linear and a-monobranched enones (e.g. 7 and 8), but lower for linear methyl ketones like 2-octanone (6). In should be noted that in the reduction of unsaturated ketones, the time of addition is critical (the optimum being around 15-20 min) in order to avoid concomitant olefin hydroboration. In sharp contrast to the CBS process, the use of catecholborane (instead of BMS) or alternative solvents proved to be detrimental. 

Becker, D. P., Flynn, D. L. Studies of the solid-phase Pauson-Khand reaction selective in-situ enone reduction to 3-azabicyclo[3.3.0]octanones. Tetrahedron Lett. 1993, 34, 2087-2090. 

Sesquiterpenes of the patchouli family were made by a synthetic sequence involving construction of tricyclo[3.2.1.0 ]octanone 25 by vinylphosphonium bicycloannulation of substituted cy-clohexenone. Lithium/ammonia reduction, with in situ methylation, gave 1,3,3-trimethyl-6-(1 -methylvinyl)bicyclo[2.2.2]octan-2-one (26) as the cleavage product, which was then converted to patchouli alcohol by further synthetic transformations. ... 

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