Cycloalkanones, methyl

CYCLOALKANONES Methyl methylthiomethyl sulfoxide. Diborane. Silver perchlorate. Sodium cyclopentadivinyldicarbonylferrate. 

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-... 

When the cyclic enone is unsubstituted, but the resulting enolate is quenched with an electrophile under conditions of kinetic control the irons adduct is formed exclusively303. Particularly successful is the sequential Michael addition/enolate alkylation in diastereoselective routes to frans-a,/j-difunctionalized cycloalkanones and lactones304-308. The key steps in the synthesis of methyl ( + )-jasmonate (3)309-310 (syn/anti diastereoselection) and (-)-khushimone (4) (syn/anti and induced diastereoselection) illustrate this sequence311 (see also Section D. 1.1.1.3.). 

Trimethylsilylketene and acyl isocyanates generate 4-trimethylsiloxy-l,3-oxazin-6-ones 12 in situ, which smoothly react with the enamines of cycloalkanones to give bicyclic 2-pyridones 13 <96TL(37)4977>. The heterocycles 12 also undergo the Diels-Alder reaction with dimethyl acetylenedicarboxylate or methyl propiolate to furnish substituted 2-pyridones <96TL(37)4973>. 

The addition of a Ni-catalyst to an alkyne as 6/4-47 and a cyclic enone as 6/4-46 in the presence of the chiral ligand 6/4-49 followed by a methyl transfer using Me2Zn led to 3-substituted cycloalkanones as 6/4-48 in good to medium yield, with an ee-... 

Of the many substituted and functionalized alkenes that have been combined with diazo dipoles to give A -pyrazolines or products derived from them (i.e., A -pyrazolines, pyrazoles, cyclopropanes), only a selection will be mentioned. These include ot-alkylidene-cycloalkanones (62), -flavanones, -thioflavanones, -chroma-nones, and thiochromanones (63,64) a-arylidene-indanones and -indolones (65) diarylideneacetones (66) l-benzopyran-2(77)-ones (coumarins) (67,68) 4-nitro-1,2-oxazoles (69) 2-alkylidene-2-cyanoacetates (70) dimethyl 2,3-dicyanofuma-rate (71) tetracyanoethylene (72) tetraethyl ethylenetetracarboxylate (72) 1,4-quinones (35,73-75) 2-X-l,l,l-trifluoro-2-propene [X = Br, (76), SPh, SOPh, S02Ph (77)] nitroalkenes (78) including sugar nitroalkenes (79) 1-diethoxyphos-phoryl-1-alkenyl-sulfoxides (80) methyl 2-(acetylamino)cinnamate and -acrylate... 

Asymmetric deprotonation of monocyclic cycloalkanones is not restricted to cyclohexanones. Thus, deprotonation of 3-phenylcyclobutanone with lithium bis[(S)-l-phenylethyl]amide in THF at — 100 °C in the presence of chlorotriethylsilane affords (—)-(/ )-3-pheny 1-1 -(triethylsi-lyloxy)-l-cyclobutene with 92% ee in 70% yield59d. Interestingly, with lithium (/ )-2,2-dimethyl-A-[( / )-2-(4-methyl-l-piperazinyl)-l-phenylethyl]propylamidc in THF/HMPA an ee value of only 47 % for the enol ether is recorded. 

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... 

Chiral 2,2-disubstituted cycloalkanones.1 The imine 2 prepared from racemic 2-methylcyclohexanone and (S)-( - )-l, reacts with methyl vinyl ketone to form an adduct that is hydrolyzed to the (R)-( + )-diketone 3 in 91% ee with recovery of 1 in almost quantitative yield. The reaction is described as a deracemizing alkylation. ... 

These products are stable when stored at 50°, can be poured at temps below 100°, and have high deton velocities. The expls can be used alone, mixed with one another, or mixed with other expls (Ref 2). Kincaid McGill (Ref 4) found that the polynitrate esters of poly(hydroxy-methyl) cycloalkanones and of poly(hydroxy-methyl) cycloalkanols are capable of plasticizing NC. They describe a flashless, nonhygio-scopic propint (NGu, NC plasticizer) which is reported superior to proplnts plasticized with a volatile HE. Derivatives of cycloalkanone which have therapeutic value were prepd by Ritzer (Ref 6)... 

The reactions of thiourea and guanidine with cycloalkanones are carried out in the same manner [101]. But it is worthwhile noting that muticomponent reactions of urea-like compounds with ketones, containing an activated methyl or methyle-negroup, often do not stop after the formation of a pyrimidine ring. In fact numerous derived condensation processes can lead to more complicated polycyclic compounds, which are especially typical for the reaction of cycloalkanones [101]. 

Aryl tellurium trichlorides condense with methyl ketones, cycloalkanones, methoxy-benzene, dimethylaminobenzene, and 1,3-dihydroxybenzene to produce unsymmetrical diorgano tellurium dichlorides under mild conditions. 

At the same time the conversion of 11/54 — 11/59 (Scheme II/9) was published, an alternative way was found, which is summarized in Scheme II/9. The lithium derivative of (phenylthio)methyl phenyl sulfone adds nearly quantitative into ketones, in the presence of diethylaluminium chloride. The rearrangement (e.g. 11/61—> 11/62) proceeds smoothly on treatment of the tertiary alcohol, 11/61, with an approximately sixfold excess of diethylaluminium chloride [46]. An alternate reagent, the lithium salt of methoxy methyl phenyl sulfone, in a similar reaction yielded, enlarged a-methoxy cycloalkanones. The latter reaction sequence is restricted to the expansion of four- and five-membered rings [46]. 

In a free radical ring expansion reaction discovered quite recently [24] [25], a methyl or ethyl cycloalkanone-2-carboxylate was first alkylated with methylene-dibromide [24] or bromomethylphenylselenide [25], Scheme VII/11. 

A large number of catalysts have been shown to be active in the oxidation of cycloalkanones to lactones using only hydrogen peroxide as the oxidant. Methyl-trioxorhenium (MTO) is moderately active in the oxidation of linear ketones [242] or higher cycloalkanones [243] but it is particularly active in the oxidation of cyclobutanone derivatives (Fig. 4.82), which are oxidized faster with MTO than with other existing methods [244]. 

The acid-catalyzed reaction of enol silyl ethers of cyclic ketones with optically active methyl 4-methylphenylsulfinate has been reported as a very efficient method for the synthesis of chiral a-sulfinyl cycloalkanones 212. Boron trifluoride-diethyl ether, titanium tetrachloride and tin(IV) chloride may all be used as catalysts, however, the reproducibility of this procedure has recently been questioned71. 

Dibutyltin bis(triflate), Bu2Sn(OTf)2, is a mild Lewis acid which catalyzes clean Michael addition of enol silyl ethers [148]. The new catalyst enables use of various labile acceptors such as methyl vinyl ketone and 2-cyclopentenone which do not undergo smooth reaction with conventional Lewis acids. A variety of enol silyl ethers are also employable and thus 2-(trimethylsiloxy)propene, the simplest of this class of compounds, can be used. The adducts of enol silyl ethers of cycloalkanones with vinyl ketones are readily cyclized to give the desired annulated enones free of isomers. Consequently, a practical version of the Robinson annulation has been realized. 

Olefination of aldehydes with the a-fluoroalkylphosphine oxide (54) provides a highly stereoselective route to the (Z)-fluoroalkenes (55) (Scheme 9).31 A similar reaction with the corresponding phosphonate gave a 1 1 mixture of ( )- and (Z)-alkenes. A new one-pot synthesis of 2-(diphenylphosphinoyl)cycloalkanes (56) by the reaction of cycloalkanone enolates with chlorodiphenylphosphine followed by oxidation has been reported (Scheme 10).32 Attempts to synthesise sarkomycin methyl ester (58) via reaction of the anion of phosphine oxide (57) with formaldehyde were unsuccessful as were similar reactions with other aldehydes, although the corresponding phosphonate anion does undergo olefination reactions. An X-ray structural analysis of (57) is reported. 

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