Reduction of Cyclohexanone with

The axial and equatorial transition structures for reduction of cyclohexanone [6] with AIH3 (3-2IG ) (Fig. 6-15) show incipient Hnu-C bond distances of 1.891 and 1.889 A. These are somewhat shorter than for LiH reduction (2.057 and 2.028 A) [28, 51], indicative of a later transition state for AIH3. 

In each transition state, the bonds which are antiperiplanar to the forming Hnu-C bond are elongated, axial C-Hs for axial attack, and C-C bonds for equatorial (Fig. 6-1). This effect has also been noted in calculations of the Diels-Alder transition states [39, 40]. Using the calculated length of the adjacent axial C-H bond of cyclohexanone (1.087 A) as a reference, a further lengthening [58] to 1.091 A (0.37%) in the axial transition state occurs, with no extension of the C -C/j bond. 

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Figure 8.11 Reduction of cyclohexanone with alcohol dehydrogenase and rhodium complex using electric power [7b].

Table 12. Rate of Equatorial Alcohol in the Reduction of Cyclohexanones with Aliphatic Grignard Reagents154-160...

An accepted pathway for the reduction of cyclohexanone with borane (B2H6) in oxacyclopentane (THF) is presented in Scheme 9.16. As shown there, it is presumed that, initially, the borane THF complex is converted to a carbonyl group borane complex (i.e., C=0 BH3) and that hydride donation from the complexed borane to the carbon of the carbonyl leads to a monoalkoxyborane. 

Scheme 9.17. A representation of the reduction of cyclohexanone with lithium aluminum hydride (LiAlH4) in ether and the hydrolysis of the aluminum alkoxide product to produce cyclohexanol.

Sn(II)] [M(III)] ratio M(III) = RhCb SHzO, IrClj SHzO, or HsIrCU on the rate and stereoselectivity of the M(III) + SnCl2 2H20 -catalyzed reduction of cyclohexanones with propan-2-ol has been reported. ... 

Complex 54 displayed a high activity in the reduction of cyclohexanone with a TOF value of 6000 h (Figure 13.7)." Tetrahydropyridoimidazolin-2-yli-dene-containing 55 was also evaluated for TH of acetophenone and cyclohexanone in z-PrOH/KOH. ° Cationic triazol-5-ylidene complexes 56 were found highly active for the TH of C=0 and C=C functions as well as for reductive amination of aldehydes. 

We recently reported that Cu/Si02 is an effective catalyst for the hydrogenation of cyclohexanones under very mild experimental conditions. Thus, a series of cyclohexanones with different substituents, including 3-oxo-steroids, could be reduced under 1 atm of H2 at 40-90°C, with excellent selectivity (5). The catalyst is non-toxic and reusable. This prompted us to investigate the reduction of cyclohexanones over a series of supported copper catalysts under hydrogen transfer (h.t.) conditions (2-propanol, N2, 83 °C) and to compare the results with those obtained under catalytic hydrogenation (n-heptane, 1 atm H2, 40-90°C) conditions. Here we report the results obtained in the hydrogenation of 4-tert-butyl-cyclohexanone, a molecule whose reduction,... 

Tributyltin hydride reduction of carbonyl compounds. The reduction of carbonyl compounds with metal hydrides can also proceed via an electron-transfer activation in analogy to the metal hydride insertion into TCNE.188 Such a notion is further supported by the following observations (a) the reaction rates are enhanced by light as well as heat 189 (b) the rate of the reduction depends strongly on the reduction potentials of ketones. For example, trifluoroacetophenone ( re<1 = —1.38 V versus SCE) is quantitatively reduced by Bu3SnH in propionitrile within 5 min, whereas the reduction of cyclohexanone (Erea — 2.4 V versus SCE) to cyclohexanol (under identical... 

Under certain conditions, the trifluoroacetic acid catalyzed reduction of ketones can result in reductive esterification to form the trifluoroacetate of the alcohol. These reactions are usually accompanied by the formation of side products, which can include the alcohol, alkenes resulting from dehydration, ethers, and methylene compounds from over-reduction.68,70,207,208,313,386 These mixtures may be converted into alcohol products if hydrolysis is employed as part of the reaction workup. An example is the reduction of cyclohexanone to cyclohexanol in 74% yield when treated with a two-fold excess of both trifluoroacetic acid and triethylsilane for 24 hours at 55° and followed by hydrolytic workup (Eq. 205).203... 

The organosilane reduction of ketones in the presence of alcohols provides an excellent route to unsymmetrical ethers. The reaction of cyclohexanone with ethanol and Et3SiH/TFA gives cyclohexyl ethyl ether in good yield.327,328 The... 

The first example of this type of transformation was reported in 1974 [76]. Three catalysts were investigated, namely [Co2(CO)8], [Co(CO)g/PBu ], and [Rh6(CO)i6]. The [Co OJg/PBu ] catalyst showed activity for reductive animation using ammonia and aromatic amines. The [Rh6(CO)16] catalyst could be used for reductive animation using the more basic aliphatic amines that were found to poison the cobalt catalyst. This early report pointed out that the successful reductive animation of iso-butanal (Me2CCHO) with piperidine involves selective enamine hydrogenation, that reductive animation of cyclohexanone with isopropylamine probably involves imine hydrogenation, and that reductive amination of benzaldehyde with piperidine would presumably involve the reduction of a carbinolamine. 

The two-phase reduction of cyclohexanones by sodium dithionite in the presence of a stoichiometric amount of Adogen gave higher yields of the cyclohexanols than those obtained by the standard procedure using sodium dithionite in a water dioxane system (Table 11.9). A marked improvement in yield was also observed with the reduction of sterically hindered 2,6-dimethylcyclohexanone and there was a greater degree of stereoselectivity, which was comparable to that noted for the corresponding reduction with the borohydride ion [4]. 

In the presence of excess ketone, a slower equilibration occurred leading to ris-3,3,5-trimethyIcyclohexanol (cis-6) almost exclusively (148). It was shown that aluminum 3,3,5-trimethylcyclohexyl alcoholate could be oxidized by the addition of cyclohexanone with corresponding reduction of the latter. These processes occur by a similar MPV oxidation-reduction mechanism, shown in a general form in Scheme 18. 

Another approach to (R)-(-)-phoracantholide I (245) used a ring enlargement of cyclohexanone (255) which had been alkylated with chiral synthon 256 (Scheme 14) [206]. Thus, compound 257 was prepared in 35% yield on a 7-g scale by alkylation of cyclohexanone with chiral 256. Cyclization with Am-berlyst A-15 provided enol ether 258 that was directly submitted to ruthenium tetroxide oxidation to give oxolactone 259 in a 47% yield. Reduction of the latter with catecholborane via its tosylhydrazone afforded (R)-(-)-phoracan-tholide I (245) in 31% yield. 

Yeast alcohol dehydrogenase (YADH), catalysis of reduction by NADH of acetone formate dehydrogenase (FDH), oxidation by NAD of formate horse-liver alcohol dehydrogenase (HLAD), catalysis of reduction by NADH of cyclohexanone With label in NADH, the secondary KIE is 1.38 for reduction of acetone (YADH) with label in NAD, the secondary KIE is 1.22 for oxidation of formate (FDH) with label in NADH, the secondary KIE is 1.50 for reduction of cyclohexanone (HLAD). The exalted secondary isotope effects were suggested to originate in reaction-coordinate motion of the secondary center. 

Reduction of cyclohexanone oxime with lithium aluminum hydride in tetra-hydrofuran gave cyclohexylamine in 71% yield [809], and reduction of ketoximes with sodium in methanol and liquid ammonia [945] or in boiling ethanol [946] afforded alkyl amines, usually in good to high yields. Stannous chloride in hydrochloric acid at 60° reduced the dioxime of 9,10-phenanthra-... 

From the readily available benzotriazole derivative 76, Katritzky and Harris (90T987) prepared a diastereomeric mixture of the /3-amino ketone 77 with the lithium enolate of cyclohexanone. In the reduction of 77 with lithium aluminium hydride, a reductive cyclization took place, resulting in the two diastereomeric oxazinones 78 in a ratio of 5 2. This cyclization can be regarded as a variation of the chloroformate cyclization under alkaline conditions. 

Preparative scale reduction of cyclohexanone affords principally the tail-to-tail hydrodimer 23 and some of the hcad-to-tail isomer 24 [93]. The proportions vary with pH, and no head-to-head pinacol has been isolated. Both meso- and ( )-forms... 

This method of preparing alcohols is an adaptation of an oxymercuration procedure of Sand and Genssler2 and reduction methods of Henbest and Nicholls.3 Other methods for preparing 1-methylcyclohexanol are oxymercuration followed by reduction in tetrahydrofuran-water 4 reaction of cyclohexanone with... 

You can also catalytically reduce aldehydes and ketones to produce 1° and 2° alcohols. Reduction conditions are very similar to those used to reduce alkene double bonds. If a molecule possesses both a double bond and an aldehyde or ketone functional group, reduction of the aldehyde or ketone group is best carried out using sodium borohydride. The reduction of cyclohexanone by hydrogen gas with a platinum catalyst produces cyclohexanol in good yield. 

The catalytic effect of DMP+ can be best demonstrated with an example. Consider the reduction of cyclohexanone 16). This substrate does not exhibit a polarographic wave, nor a CV reduction peak (Fig. la and 2a). On the other hand, DMP+ shows... 

In contrast, sterically undemanding hydride donors such as NaBH4 or LiAlH4 reduce 4-fert-butylcyclohexanone preferentially through an axial attack. This produces mainly the cyclohexanol with the equatorial OH group (Figure 8.8, middle and bottom reactions). This difference results from the fact that there is also a stereoelec-tronic effect which influences the diastereoselectivity of the reduction of cyclohexanones. 

Propose a mechanism for both parts of the Wolff-Kishner reduction of cyclohexanone the formation of the hydrazone, then the base-catalyzed reduction with evolution of nitrogen gas. 

Fig. 32 Reduction of cyclohexanone catalyzed by HLADH with simultaneous hydrogenase-driven regeneration of NADH in an organic-aqueous two-phase system...

Several organic solvents were investigated with regard to stability and activity of HLADH as well as their influence on the hydrogenase-driven reaction. Hydrophobic solvents such as heptane or toluene proved to be the most suitable solvents for the coupled enzyme-system. Furthermore, it became apparent that nonimmobilized cells, permeabilized with cetyl-trimethylammonium bromide, showed the best results for NADH regeneration. After optimization the conversion in heptane with 10% water yields 99% cyclohexanol by reduction of cyclohexanone. 

Especially worth mentioning in a green context is the use of mesoporous materials and zeolites, as stable and recyclable catalysts for MPV reductions. High activity was obtained by using zeolite-beta catalysts. Beta zeolites have a large pore three-dimensional structure with pores of size 7.6 x 6.4 A2 which makes them suitable for a large range of substrates. Al, Ti- and Sn-beta zeolite have all been used as catalysts for the selective reduction of cyclohexanones [40-42]. The... 

Cieplak ° countered the Anh explanation with an alternative orbital model. He noted that reductions of cyclohexanones and other additions at carbonyls occasionally resulted in the major product coming from the Eelkin-Anh minor TS. Arguing that since the incipient bond was electron deflcient—a partial bond lacks the full two-electron occupation—it is donation of density from the Oc2-l into the Oc-nuc oi ital that will stabilize the TS (Scheme 6.3). Support for the Cieplak model was provided by experimental results for nucleophilic addition to... 

Tetraalkyl- and tetraatyl-ethylene glycols (pinacols) are made by reduction of ketones with active metals such as sodium, magnesium, and aluminum. The reaction is only fair for aliphatic and alicyclic ketones. Acetone, methyl ethyl ketone, cyclopentanone, and cyclohexanone all give less than 0% yields of pinacols. Mixtures of ketones are reduced to unsymmetrical pinacols. An active zinc-copper couple has been employed in the reduction of several simple olefinic aldehydes to dieodiols, e.g., crotonaldehyde to dipropenyl glycol,... 

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