Ketones intramolecular reactions

As in the reactions with aldehydes and ketones, intramolecular reactions are easy (Scheme 39), and the reaction is selective for the formation of the product with the substituents syn on the carbon chain, whatever the geometry of the double bond in the allylsilane (Scheme 40). However, this clean stereoselectivity is not seen with the acetals of aromatic aldehydes, where the choice of Lewis acid and the nature of para substituents affect the proportion of the diastereoisomers. 

The use of oximes as nucleophiles can be quite perplexing in view of the fact that nitrogen or oxygen may react. Alkylation of hydroxylamines can therefore be a very complex process which is largely dependent on the steric factors associated with the educts. Reproducible and predictable results are obtained in intramolecular reactions between oximes and electrophilic carbon atoms. Amides, halides, nitriles, and ketones have been used as electrophiles, and various heterocycles such as quinazoline N-oxide, benzodiayepines, and isoxazoles have been obtained in excellent yields under appropriate reaction conditions. 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

No intennolecular reaction of malonate or /3-keto esters with halides has been reported, but the intramolecular reaction of /3-diketones such as 790 and malonates proceeds smoothly[652,653]. Even the simple ketone 791 can be arylated or alkenylated intramolecularly. In this reaction, slow addition of a base is important to prevent alkyne formation from the vinyl iodide by elim-ination[654]. 

In a similar manner, ketones can react with alcohols to form hemiketals. The analogous intramolecular reaction of a ketose sugar such as fructose yields a cyclic hemiketal (Figure 7.6). The five-membered ring thus formed is reminiscent of furan and is referred to as a furanose. The cyclic pyranose and fura-nose forms are the preferred structures for monosaccharides in aqueous solution. At equilibrium, the linear aldehyde or ketone structure is only a minor component of the mixture (generally much less than 1%). 

Ring formation by intramolecular reaction between an allylsilane and an aldehyde or ketone is well precedented54, 55. 

Chelation control of the intramolecular reaction between an allylsilane and an aldehyde or ketone has been carefully investigated. Excellent stereoselectivity was found for cyclization of B-oxo esters using titanium(IV) chloride as the Lewis acid, less good selectivity for cyclization of /l-diketones70. 

Lithium fefrafc/s-(3,5-ditrifluoromethyl)borate, which provides an unsolvated lithium cation in noncoordinating solvents, exhibits a several thousandfold catalysis of the reaction of cyclopentadiene and methyl vinyl ketone.37 Lithium tetrafluoroborate is also an effective catalyst and in some instances has worked when LiC104 has failed, such as in the intramolecular reaction shown below.38... 

The aldehyde or ketone group of monosaccharides can undergo an intramolecular reaction with one of its own hydroxyl groups to form a cyclic, hemiacetal, or hemiketal structure, respectively (Figure 1.26). In aqueous solutions, this cyclic structure actually predominates. The open-chain aldehyde or ketone form of monosaccharides is in equilibrium with the cyclic form, but the open structure exists less than 0.5 percent of the time in aqueous environments. It is the... 

The reaction does not tolerate simple ketones, but reactions of activated ketones, cr-diketones, or cr-keto esters with arylstannes3813 and intramolecular reactions395 are possible (Equations (40) and (41)). 

Electrophilic substitution reactions on alkynylsilanes are also known. In 1978 K. Ultimootd, M. Tanaka and coworkers by an intramolecular reaction carried out the synthesis of a macrocyclic ketone. 

The last question still open addresses the alkynyl ketones. The reaction of 64 shows an example with a potential intramolecular competition and here it is possible to isomerize the propargyl substitutent on the ketone quantitatively without changing the 1-hexynyl substituent on the other side [125] (Scheme 1.28). From the publication it is not clear whether the isomerization is really a thermal reaction or occurs during the workup of the thermolysis reaction, for example by chromatography (compare the discussion above [110]). 

Crossover experiments have been used to establish that the novel N to C acyl migration reaction of acyclic imides (69), to give o -amino ketones (70), proceeds by intramolecular reaction of the base-generated carbanion. ... 

An alternative strategy to access cross-benzoin products is to tether the two reactive parmers. This approach has the disadvantages inherent to intramolecular reactions, but it provides access to products produced by the coupling of aldehydes with ketones, hi... 

A Piperidine acts both as a nucleophile and as a base. First it combines with the pyrylium cation at C-2, forming an adduct which then ring opens, deprolonates and tautomerizes to an enamino ketone (Schema 4.3), This product cyclizes through an intramolecular reaction between the enamine unit and the carbonyl group, followed by dehydration to form the phenylpiperidine. 

Oxetanes can be formed by intramolecular reaction between a carbonyl group and an alkene, and this has been used (4.74) in making analogues of thromboxane A, (one of the compounds responsible for the control of blood clotting), albeit usually as the minor product. A special case of intramolecular reaction is seen for a,p-unsaturated carboxylic acids 14.75), where the product is an oxete that is tautomeric with a p-lactone. Oxetes may also be formed by photocycloaddition of ketones or aldehydes with alkynes the oxete normally ring-opens at room temperature to give an a,p-unsaturated carbonyl compound (4.76), but at lower temperatures its spectral... 

Certain unsaturated aldehydes may be converted to cyclic ketones by a related mechanism. The formyl group reacts with Rh(I) complexes to form an acyl-Rh hydride species, which undergoes intramolecular reaction with the olefinic linkage present in the same molecule (117a). Asymmetric induction is observed with a chiral diphosphine ligand (Scheme 53) (117b-d). Enantioselective cyclization of 4-substituted 4-pentanals into 3-substituted cyclopentanones in greater than 99% ee is achieved with a cationic BINAP-Rh complex. 

Reactivity in the elimination reaction is probably largely determined by the nature of the substituents (in addition to hydrogen) attached to the y-carbon atom. If the reaction is stepwise, one would expect faster reaction with either 2-hexanone or methoxyacetone than with 2-pentanone, because the biradical intermediates would be more stable in the former two cases. Such a conclusion follows from the similarity shown by various ketone triplets in intermolecular reactions333 to the known selectivity of attack by /-butoxy radicals in both inter-353 and intramolecular reactions.354... 

The reaction is carried out in vapour phase (250°C) using a flow system (see methods section). This procedure turned out to be essential in order to mantain the hydrogen transfer as the main reaction pathway. A batch experiment carried out in an autoclave actually showed a wide range of condensation products besides some saturated ketone [6]. Reactions of ketones over oxide catalysts can lead to a variety of products due inter alia to aldol condensation, intramolecular dehydration and intermolecular disproportionation [16]. However, the presence of a good hydrogen donor such as a secondary alcohol and vapour phase conditions favour the transfer hydrogenation as the major reaction [16,17]. In our reaction conditions, products attributable to crotonic condensations and subsequent 1,4 Michael addition [18] were observed by g.l.c.-m.s. (Table 1). 

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