Ketones, with Cyclic

These reactions give as intermediates the substitution products 258 that undergo spontaneous cyclization in good yields. Most of the examples studied involve carbanions derived from ketones. With cyclic ketones, such as cyclohexanone320, the yields are lower. 

Oxidative Cleavage of l,2-Diols7 1,2-Diols are cleaved by Mn02 to aldehydes or ketones. With cyclic 1,2-diols, the reaction leads to dialdehydes or diketones (eqs 33 and 34) and the course of the reaction depends on the configuration of the starting material (eqs 34 and 35). ... 

Oxidative olefination. The first example of oxidative olefina-tion was reported by Yi and Lee. ° Since then many examples of olefination reactions have been reported. In Lee s system the active complex [RuH(CO)(PCy3)(C6H6)]BF4 was used to catalyse the inter-molecular dehydrative coupling reaction of aromatic ketones with cyclic alkenes to give a 1 1 mixture of two alkene isomers. Both cyclopentene and cyclohexene were found to be suitable substrates, but other sterically demanding alkenes such as cyclooctene and methylcyclo-pentene afforded the coupling products in poor yields. 

The Diels-Alder reaction of cyclopropenyl ketones with cyclic dienes and 2,3-dimethylbutadiene yielded substituted tricyclo[3.2.2.0 " ]non-6-ones in high yields (90%). The inter- and intra-molecular Diels-Alder reactions of 2-halocycloalkenones with dienes formed [4,2,0]octenones. The 2-bromocycloalkenones are highly reactive and endo-sdective. ... 

Reaction of cyclic ketones with diazoraethane leads to ring enlargement. Thus cyctohexanone (I) (1 mol) and diazomethane (1 mol) give /oheptanone (II) in about 60 per cent, yield together with a little epoxide (III) as by product and some cj/cioootanone (IV) resulting from further reaction of cyctoheptanone with diazomethane. ... 

An interesting aspect of this reaction is the contrasting stereoselective behaviour of the dimethyisulfonium and dimethyloxosuifonium methylides in reactions with cyclic ketones (E.J. Corey, 1963 B, 1965 A C.E. Cook, 1968). The small, reactive dimethyisulfonium ylide prefers axial attack, but with the larger, less reactive oxosulfonium ylide only the thermodynamically favored equatorial addition is observed. 

With cyclic ketones, the a-cleavage can also be followed by intramolecular bydn en abstraction that leads eventually to an unsaturated ring-opened aldehyde ... 

There is some spectral evidence that acylation of enamines of cyclic ketones with acid chlorides having an a-hydrogen in the presence of triethylamine proceeds via the ketene and subsequent cycloaddition (84). The intermediate cyclobutanone is then opened to give the enamino ketone which is hydrolyzed to the 2-acyl cyclohexanone. In the case of enamines of larger cyclic ketones the alternate mode of the cyclobutanone opening predominates, with the formation of ring-expanded 1,3-diketones upon... 

The reaction of the enamines of cyclic ketones with alkyl isocyanates, acyl isocyanates, phenyl isothiocyanates, and acyl isothiocyanates has also been reported 112). The products are the corresponding carboxamides. The products from the isothiocyanates have been utilized as intermediates in the preparation of various heterocyclic compounds 113). 

The reaction of morpholine enamines of cyclic ketones with ethyl azodicarboxylate has also been demonstrated 56,136). The enamine (113) on reaction with ethyl azodicarboxylate can give the 2- or 2,6-bis(N,N di-carboxyhydrazino)cyclohexanones 199 and 200, respectively, on hydrolysis. 

From the reactions of sulfur and carbon disulfide with cyclic ketone-derived enamines (570-573) 3H-l,2-dithiole-3-thiones were obtained, whereas the addition of carbon disulfide to other enamines gave a-dithio-pyrones (574), through initial dimerization of the enamine. 

Transition metal catalysis in Baeyer-Villiger oxidation of cyclic ketones with formation of lactones 98AG(E)1198. 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

With cyclic a-halo ketones, e.g. 2-chloro cyclohexanone 6, the Favorskii rearrangement leads to a ring contraction by one carbon atom. This type of reaction has for example found application as a key step in the synthesis of cubane by Eaton and Cole for the construction of the cubic carbon skeleton ... 

With cyclic a-diazo ketones, e.g. a-diazo cyclohexanone 9, the rearrangement results in a ring contraction by one carbon " ... 

Cyclic 1,3-diacetoxy-l,3-dienes can be generated in situ from cyclic 1,3-diketones under the influence of isopropenyl acetate. The dienes then undergo Diels-Alder reactions with maleic anhydride giving as products 1-acetoxybicycloalkane dicarboxylic anhydride derivatives (10). The procedure is also successful with cyclic 1,2- and 1,4-diketones as well as cyclic a,j3-unsaturated ketones. The products, after hydrolysis to... 

Allylic nitro compounds are obtained by the reacdon of cyclic ketones with nitromethane in the presence of 1,2-diaminoethane fl mol% as catalyst. Because exa-cyclic nitroalkenes are rearranged to the fi)iifo-cyclic fi,Y-nitroalkenes, allylic nitro compounds are selecdvely produced fEq. 3.21. ... 

Treatment of a cyclic ketone with diazomethane is a method for accomplishing a ring-expansion reaction. For example, treatment of cyclohexanone with diazomethane yields cycloheptanone. Propose a mechanism. 

Alkyl A-(3-oxobuten-l-yl)-2-aminobenzyl ketones 9 (as their cyclic acetals), formed by condensation of alkyl 2-aminobenzyl ketones with 3-methoxybut-3-ene-2-one, undergo acid-catalyzed cyclization to give rare examples of A -unsubstituted 1H-1 -benzazepines 10 in high yields.81... 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

The methodology of precomplexing a cyclic ketone with MAD, followed by addition of a nucleophile, has also been successfully used for the mcthylation of 5a-cholestan-3-one (7). Thus, addition of methyllithium4 or methylmagnesium iodide57 to the steroidal ketone affords predominantly 3/ -methyl-5a-cholestan-3a-ol, whereas alkylation with melhyllithium/MAD almost exclusively affords 3a-methyl-5a-cholestan-3/J-ol via predominant axial attack of the nucleophile4. 

The reaction of the enamines of cyclohexanones with a,ft-unsaluraled sulfones gives mixtures resulting from attack of the enamine at the a- and /(-carbons of the oc,/ -unsaturated sulfone. The ratio of x- and /1-adducts is dependent upon the reaction solvent, the geometry and structure of the sulfone1 4. The diastereoselectivity of these reactions is also poor. The reaction of lithium enolates of cyclic ketones with ( )-[2-(methylsulfonyl)ethenyl]benzene, however, gives bicyclic alcohols, as single diastereomers, that result from initial -attack on the oc,/ -unsaturated sulfone5. 

HOHC[C(CH2OH)2]4CHOH, mw 356.36, can be prepd by reduction of the corresponding diene . Octamethylolcyclohexanedione, OC[C(CH2OH)2]4CO, mw 352.33, can be prepd by condensation of the corresponding cyclic ketone with aldehyde... 

Both of these compds yield expls on nitration. It is claimed that these expis have a high detonation velocity, can be pouted at temps below 100°, and are stable when stored at 50° The same investigators proposed the use of nitrates of other cyclic keto-alcohols, such as tetramethylolcyclohexanone, tetramethylolcyclo-pentanone, etc, as expls. All of these alcohols can be prepd by condensing cyclic ketones with formaldehyde in the presence of alkalies or al-... 

This reagent reacts with a,/3-unsaturated ketones to give kinetic products of exclusive 1,4-addition (2). With cyclic substrates, a strong preference for axial addition is observed, as is a susceptibility to steric hindrance. Transformation into the corresponding silylcuprate species permits conjugate addition to a wider variety of a,/3-unsaturated substrates (3,4). 

Direct treatment of TIPS enol ethers of a variety of cyclic and acyclic ketones with the strong-base combination of n-BuLi/KO-t-Bu leads to /3-ketosilanes (2) after aqueous work-up. In contrast with the earlier method, this rearrangement appears to proceed through allylic, rather than vinylic, metallation, since enol ethers lacking an allylic a-proton are unreactive. 

Indium trichloride [30] and methylrhenium trioxide [31] catalyze the aqueous Diels-Alder reaction of acrolein and acrylates with cyclic and open-chain dienes. Some examples of the cycloaddition of methyl vinyl ketone with 1,3-cyclohexadiene are reported in Scheme 6.18. MeReOs does not give satisfactory yields for acroleins and methyl vinyl ketones with substituents at the jS-position and favors the self-Diels-Alder reaction of diene. 

Non-Kolbe electrolysis of alicyclic p-hydroxy carboxylic acids offers interesting applications for the one-carbon ring extension of cyclic ketones (Eq. 35) [242c]. The starting compounds are easily available by Reformatsky reaction with cyclic ketones. Some examples are summarized in Table 13. Dimethylformamide as solvent and graphite as anode material appear to be optimal for this reaction. 

In the presence of metal catalysts such as rhodium compounds, aldehydes can add directly to alkenes to form ketones. The reaction of co-alkenyl aldehydes with rhodium catalyst leads to cyclic ketones, with high enantioselectivity if chiral ligands are employed. Aldehydes also add to vinyl esters in the presence of hyponitrites and thioglycolates. ° ... 

Both dimeric and trimeric cycloaikylidine peroxides can be synthesized by treatment of the corresponding cyclic ketones with H2O2 in acid solution. The trimeric peroxide is formed first and is subsequently converted to the dimeric compound. ... 

With alkyl aryl ketones, it is the aryl group that generally migrates to the nitrogen, except when the alkyl group is bulky. The reaction has been applied to a few aldehydes, but rarely. With aldehydes the product is usually the nitrile (16-21). Even with ketones, conversion to the nitrile is often a side reaction, especially with the type of ketone that gives 17-31. A useful variation of the Schmidt reaction treats a cyclic ketone with an alkyl azide (RN3) in the presence of TiCU, generating a... 

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