Cycloheptanone reduction

Hydrazones treated with alkalis decompose to nitrogen and hydrocarbons [845, 923] Woljf-Kizhner reduction) (p. 34), and p-toluenesulfonylhydra-zones are reduced to hydrocarbons by lithium aluminum hydride [812], sodium borohydride [785] or sodium cyanoborohydride [813]. Titanium trichloride hy-drogenolyzes the nitrogen-nitrogen bond in phenylhydrazones and forms amines and ketimines which are hydrolyzed to the parent ketones. Thus 2,4-dinitrophenylhydrazone of cycloheptanone afforded cycloheptanone in 90% yield [202]. 

The direct reduction itself may be suppressed by adding the tributyltin hydride slowly over several hours, thus keeping its concentration as low as possible. In this case, however, consecutive rearrangements sometimes lead to different products.1,2 Stereochemistry may be a decisive factor for the outcome of the rearrangement.1-1 4 For example, in the bicyclo[3.2.0]hept-2-en-6-one series, the exo-derivative exo-1 underwent ring enlargement to a cycloheptanone 2, while the e c/o-diastereomer enclo-1 reacted at the C —C double bond to form a tricyclic isomer 3.1-2... 

The cyclotrimerisation of dimethylcyclopropene is effected by Wilkinson s catalyst RhCl(PPh3)3 to provide a rhodacycloheptane derivative 111 which has been structurally characterised (Fig. 35). The metallacycle is cleaved upon treatment with carbon monoxide to provide both cyclohexane (reductive eliminations) and cycloheptanone (CO insertion) products (Scheme 34).120... 

While this methodology could be extended to more-substituted cyclooctene oxides (Scheme 56, Equation 12), examination of cycloheptene oxide (Scheme 56, Equation 13) revealed the need for considerably longer reaction times, leading to reduced yields due to competing carbenoid-insertion pathways (cycloheptanone formation and reductive alkylation) <2002AGE2376, 2003OBC4293>. 

In hydrogenolyses with HAICU, the dimethyl acetals of cyclobutanone and cyclohexanone are cleaved more slowly than that of 3-pentanone, while those of cyclopentanone and cycloheptanone are cleaved more rapidly (Table 1), as would be expected for a carbonium ion process. The differences in rate are small, suggesting that carbonium ion character is not strongly developed in the transition state. With the dimethyl acetal of 4-t-butylcyclohexanone, the hydride addition step occurs with strongly predominating axial addition when HAlCh is used Zn(BH4)2 with TMS-Cl, and TMS-H with TMSO-Tf are less selective (Table 2). Equatorial attack predominates, however, in the reduction of the ketone itself with TBDMS-H and TBDMS-OTf. ... 

The symmetrical diols derived from cyclopentanone and cyclohexanone can similarly be converted to ring-expanded ketones in good yield. The diols from reductive coupling of cycloheptanone and cy-clooctanone give mainly the corresponding dienes in aqueous acid, especially when heated, but Chris-tol found that pinacol rearrangement is strongly favored even for these materials when cold concentrated sulfuric acid is used as the solvent. 

Cycloheptanone oxime can be converted into the amine in good yield by high-pressure hydrogenation of the oxime with Raney nickel and ammonia, but Freifelder " found that the reaction is so strongly exothermal that on a large scale it may get out of hand. He then found that the hydrogenation can be accomplished smoothly by low-pressure hydrogenation in the presence of rhodium-alumina. The temperature was allowed to rise spontaneously to 60° and kept there until reduction... 

CHg linkage. Hydrogenation of this compound yields, however, a hydrocarbon CuHaa, IR-data of which are very similar to but not identical with the curve of i-butylcycloheptane, obtained by synthesis (84) from 4-i-butylcyclohexanone by ring enlargement with diazomethane, followed by Kishner-Wolf reduction of the i-butyl-cycloheptanone. 

A prediction of the reduction of the conformationallv flexible cycloheptanones is difficult. Thermodynamically controlled Meerwein-Ponndorf-Verley conditions (30 h reflux) reduce 2-methylcycloheptanone, yielding a mixture of cis- and trcws-2-methylcycloheptanols [d.r. (cisi trans) 27 73]174... 

The asymmetric synthesis of 2-substituted cycloheptanamines (R = CII3, Et, / -Pr, C6H5, Bn) from racemic cycloheptanones by means of reductive amination has also been described27. Again, the optically active auxiliary (S )- or (/ )-a-phenylethylamine was used as the source of chiral information. 

Reduction, Tropolones are fairly resistant to reducing agents. Catalytic hydrogenation in the presence of Raney nickel or Adams catalyst provides a variety of products including cycloheptanone, cycloheptanol and cycloheptane-1,2-diol derivatives. 

Reduction. Tropone is very readily hydrogenated to cycloheptanone in the presence of a palladium catalyst. It is reduced by... 

The stereochemistry of reduction by dialkylboranes of ketones, including 2-methyl-cycloheptanone and 2-methylcyclo-octanone, has been surveyed. Invariably the dialkylboranes approach the ketone from the less hindered side to give the less stable alcohol product. The stereochemistry of reduction of 2-ethoxycarbonylcyclo-alkanones to 2-hydroxycycloalkane carboxylates with sodium borohydride and hydrogen-Raney nickel, have been compared. ... 

Under slightly different conditions, using 1,3-propanedithiol, acyloins and acyloin acetates lead to the formation of 1,3-dithianes where hydrogen has replaced the hydroxyl or acetoxyl groups . Hydrolysis to the ketone provides a method of converting acyloins to ketones and desulphurization allows conversion of acyloins to hydrocarbons (equation 10). Reduction of l,l-dimethyl-5-hydroxysila-4-cycloheptanone gave l,l-dimethylsila-4-cycloheptanone by this method (equation 11) . A similar reaction is believed to be involved in the action of D-proline reductase . ... 

A proposed mechanism for the formation of cycloheptanone 228 is illustrated in (Scheme 102). The reaction is believed to proceed through precoordination of the metal to the double bond of the allene that is proximal to the cyclobutane. Insertion and C—C bond cleavage leads to metallacycle P-II. CO insertion gives either intermediate P-III or P-IV, and reductive elimination provides the [6-1-1] cycloadduct 228. 

Bromocycloheptanone is reduced to cycloheptanone by titanocene dichloride and magnesium. Vinyl acetates, including 1- and 2-acetoxycyclohepta-1,3-dienes, have been prepared from vinyl bromides using copper(i) acetate. a-Formylcyclo-heptanone reacts with 2,2-dimethyl-3-dimethylamino-2ff-azirine to give adduct (320). Electrochemical reduction of some seven-membered cyclic P-diketones has been studied polarographically/ ... 

Acyl radicals, produced by fragmentation of acyl selenides, such as 16, derived from 2,3-0-isopropylidene-L-eryrAro-furanose, undergo 6-exo and 7-endo cyclisation leading to cyclohexanones and cycloheptanones respectively. Selenide 16, incorporating an alkynyl chain extension, leads to bicycle 17 (as a mixture of four diastereomers) via a 7-endo-S-exo tandem cyclization (Scheme 5). Reductive cyclization of aldehyde 18 (prepared from D-glucose), which proceeds formally via a Sm-complexed alkoxy-stabilized radical, has been exploited in a... 

A soln. of 4 kg. cycloheptanone in methanol treated with hydroxylamine hydrochloride, stirred 1 hr. at 80°, then aq. NaOH added during 4 hrs. at the same temp., refluxed 1-2 hrs., the resulting crude oxime (Y 86%) dried, dissolved in methanol, and hydrogenated with 5%-rhodium-on-alumina at 0.75-1 atm. whereby the temp, rises gradually to 60° and is maintained there until reduction is complete -> cycloheptylamine. Overall Y 80%. M. Freifelder, W. D. Smart, and G. R. Stone, J. Org. Ghem. 27, 2209 (1962). 

Photochemical Reactions. Photolysis of (49) gives a low yield of 4-methylene-cycloheptanone and photolysis of (50a) and its cis-isomer in the presence of a reducing solvent gives (50b) the mechanism of the latter reaction has been studied by deuterium-labelling. The reducing solvent is needed even though a net reduction has not occurred. 

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