Cycloalkanones, reduction

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Reduction, carboxyl groups, 56,83 Reduction of a,0-unsaturated p-toluene-sulfonyl-hydrazones to alkenes, 59,42 Reductive alkylation, 56,52 Reductive cleavage, 56, 101 Resolution of amines, 55,80, 83 Rexyn 201,55,4 Rhodium(III) oxide, 57, 1 Ring contraction, 56, 107 Ring expansion of cycloalkanones to cycloalkenones, 59, 113... 

Barton put forward the following ideas on the reduction of alkyl cycloalkanones on the basis of conformation. 

Pyridinophanes (96) can be constructed from bis-(/3-chlorovinyl ketonic) intermediates upon treatment with ammonia. Wolff-Kishner reduction of (96) gives the parent (3,5)pyridinophane (68HCA2027). Some /3-aminovinyl carbonyls have been condensed with cycloalkanones in the presence of triethylamine and piperidinium acetate to give the (2,3)pyridinophane series (97) (70TL3291). 

In a similar fashion, reductive alkylation of benzene, toluene, and xylenes with ben-zaldehyde, aromatic methyl ketones, and cycloalkanones can be induced by InCl3 in the presence of Me2SiClH 429... 

Reduction of N-benzylimines.2 Borch reduction of imines (4, 450) to amines is not stereoselective, although reduction to equatorial amines is somewhat favored. Reductions with 1 and a number of dialkylcyanqborohydrides are much more stereoselective. Thus substituted cycloalkanone imines are reduced mainly to axial amines. However, highest selectivities are obtained with lithium tri-sec-butylborohy-dride (4, 312). 

Cycloalkenyllithiums.3 Alkenyllithiums are usually prepared by reductive lithiation of trisylhydrazones of ketones with butyllithium, but this method fails with the hydrazones of cyclic ketones. However, the cycloalkenyl sulfides, prepared by reaction of cyclic ketones with thiophenol, can be reductively lithiated with LDBB at -78°. This lithiation fails in the case of cyclopentenyl sulfides, but is useful in the case of the vinyl sulfides obtained from 6-, 7-, and 8-membered cycloalkanones. 

Cyclic Ketone Alcohols or Cycloalkanones They are prepd by condensation of the corresponding cyclic ketones with formaldehyde in the presence of alkali. They are converted by reduction into cyclic alcohols. Friederich (Ref 1) found that cyclic ketone alcohols (such as tetramethylol-cyclopentanone, tetramethylolcyclohexanone octamethylolcyclohexanedione) and cyclic alcohols (such as tetramethylolcyclopentanol, tertramethylolcyclohexanol, octamethylolcyclo-hexanediol) on nitration yield expl products. 

The stereochemical outcomes of the reductions of cyclic imino derivatives often display surprisingly great differences from those obtained with cycloalkanones and, in fact, attenuations or even reversals in stereoselectivity are common. ... 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

Allenyl-substituted cycloalkanones have also been studied the one-electron reduction of these resulted in 5-exo-trig or 5-endo-trig cyclizations (depending on the relative position of the allene group) [95]. The reductive cyclization of ketones in the presence of acrylate side-chains have been investigated the reductant was magnesium metal in methanol [96]. 

The cyclohexenone (212) is photochemically reactive in methanol and affords the bicyclic derivative (213) by a 1,2-phenyl migration in a di-m-methane rearrangement. This is accompanied by and the cyclohexenone (214) presumably formed by a reduction-elimination pathway. Change of solvent to benzene afforded only bicyclic compound (213).t three enones (215) undergo photo-rearrangement to the two products (216) and (217). The reaction appears to be solvent independent in that the same rearrangement products are obtained in benzene, t-butanol, or acetonitrile. The first compound (215, R=CF ) does behave differently in t-butanol and acetonitrile in that the rearrangement is accompanied by the cycloalkanone (218). ... 

GABA-related cycloaliphatic amino acids have also been prepared by reductive amination of the corresponding cycloalkanones in 60-80% yield and with 94-100% ee31. 

The reduction of iV-diphenylphosphinyl imines of substituted cycloalkanones with lithium tri-sw-butylborohydride (L-Selectride) provides highly diastereoselective conversions to protected axial primary amines in 83-96% yield17. The reduction of cyclohexylidene diphenylphos-phinyl imines with sodium borohydride is less diastereoselective17. 

The configuration of the asymmetric carbon in the a-position, with respect to the carbonyl group, is S whereas in the corresponding cycloalkanones it is R (see Section 2.5.1.3.2.1.). In this context it is interesting to note that the reduction of ot,/J-unsaturated ethyl ketones with B. sulfurescens also produces saturated ketones with R configuration49. 

The 4-(chloromethyl)isoxazole 13, which is readily accessible from 3,5-dimethyloxazole, serves as a C4-building-block in annulations to cycloalkanones (isoxazole annelation according to Stork). The primary step is alkylation leading to product 14, a masked triketone. On hydrogenation, the isoxazole ring is reductively opened and cyclization via the enaminone 15 leads to the enamine 16. On treatment with sodium hydroxide, this is converted into the bicycloenone 17 by hydrolysis, acid fission of the y dicarbonyl system and an intramolecular aldol condensation (analogous to a Robinson annu-lation) ... 

Aramendia, MA Borau, V Jimenez, C Marinas, JM Ruiz, JR Urbano, FJ. Meerwein-Ponndorf-Verley reduction of cycloalkanones over magnesium-aluminum oxide. Journal of the Chemical Society Perkin Transactions, 2002 2, 1122-1125. 

MgAl-LDO is also an acUve catalyst for the Meerwein-Ponndorf-Verley reduction of cycloalkanones and substituted cyclohexanones, with the conversion ovct... 

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