Alkenes haloketones

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Phosphonothiazolylmethanes 40 react with carbonyl compounds to give the expected alkene products via Knoevenagel or Homer-Wadsworth Emmons reactions. When they are treated with oc-haloketones, pyrrolothiazoles 42 are obtained in a two stage process via the quaternary salt 41 <98PSS251>. 

In intermolecular cyclopropanations [100], it was found better to use a-bromoesters and amides as ylide precursors and a,/ -unsaturated ketones and esters as electron-deficient alkenes - rather than using a-haloketones as the ylide precursor. (For experimental details see Chapter 14.11.4). The reaction gives access to a range of 1,2-dicarbonyl-substituted cyclopropanes (see Fig. 10.5). The al-kene could have an aryl-, alkyl- or indole-substituted ketone, and a-substitution was also tolerated. Notably, Weinreb amides could be used as the ylide precursor and the product subsequently transformed into a diketocyclopropane. Both enan-... 

This reaction is similar to the attack of an alkene on a halogen, resulting in addition of the halogen across the double bond. The pi bond of an enol is more reactive toward halogens, however, because the carbocation that results is stabilized by resonance with the enol —OH group. Loss of the enol proton converts the intermediate to the product, an a-haloketone. We can stop the acid-catalyzed reaction at the monohalo (or dihalo) product because the halogen-substituted enol intermediate is less stable than the unsubstituted enol. Therefore, under acid-catalyzed conditions, each successive halogenation becomes slower. 

Substituted bicyclo[ . 1.0]alkanes may also be obtained by condensation of secondary amines with 2-haloketones. A variety of nucleophilic reactions can be carried out on the intermediate cyclopropaniminium salt 116251 (Scheme 108). Competing alkene scission and cyclopropanation occurs on reaction of enamines with pentacarbonyl-chromium carbene complexes252 (Scheme 109). N-Silylated allylamines and their derived N-silylated enamines undergo rhodium or copper catalysed cyclopropanation by methyl diazoacetate253 (Scheme 110). 

One solution is a [2,3] sigmatropic rearrangement of a sulfonium ylid. A stable allylic thiol reacts cleanly with an a-haloketone 64 to give a sulfide and hence the sulfonium salt after ethylation. Only a weak base is need to make the ylid 65 as this is also an enolate. Notice the regioselectivity here the alternative ylid would also be stabilised but only by an alkene. The [2,3] shift joins the allylic fragment to the enolate of the ketone and at the same time turns it inside out. This automatically produces the more difficult product 63 after desulfurisation with Raney nickel. We shall see alternative solutions to this problem later in the chapter.9... 

Free radicals from a-haloketones. alkenes results in coupling products. 

For the enantioselective preparations of chiral synthons, the most interesting oxidations are the hydroxylations of unactivated saturated carbons or carbon-carbon double bonds in alkene and arene systems, together with the oxidative transformations of various chemical functions. Of special interest is the enzymatic generation of enantiopure epoxides. This can be achieved by epoxidation of double bonds with cytochrome P450 mono-oxygenases, w-hydroxylases, or biotransformation with whole micro-organisms. Alternative approaches include the microbial reduction of a-haloketones, or the use of haloperoxi-dases and halohydrine epoxidases [128]. The enantioselective hydrolysis of several types of epoxides can be achieved with epoxide hydrolases (a relatively new class of enzymes). These enzymes give access to enantiopure epoxides and chiral diols by enantioselective hydrolysis of racemic epoxides or by stereoselective hydrolysis of meso-epoxides [128,129]. 

Rhodium(II)-catalyzed reactions between diazosulfones and aldehydes yielded an entry to carbonyl ylides, which underwent inter- and intra-molecular cyclization reactions with dipolarophiles, such as alkynes and alkenes, to afford tetrasubstituted furans in modest to good yields <01SL646>. The rhodium(ll) acetate catalyzed reaction of 3-diazobenzopyran-2,4(3 -dione with terminal alkynes provided a mixture of 2-substituted furo[3,2-c]coumarin and furo[2,3-f ]coumarin, presumably through a formal [3+2] cycloaddition reaction <01S735>. Furo[3,2-c]coumarins were also produced from 4-hydroxycoumarins and a-haloketones via a tandem 0-alkylation-cyclization procedure <01TL3503>... 

The Pd-catalyzed reaction of y-haloketones takes place selectively via a 6-0-endo process as shown in Scheme 14. The other possible processes, such as 6-C-endo and 4-C-exo, do not appear to detectably compete with the 6-0-endo process. This is true even in cases where the 6-C-endo process can, in principle, give benzenoid aromatic compounds. Also noteworthy is that little or no exocyclic alkene-containing products are detectable. Some representative results supporting the generalizations made above are shown in Scheme 4S ... 

A variety of other reaction conditions have been examined for acylation of alkenes by acid chlorides. With the use of Lewis acid catalysts, reaction typically occurs to give both enones and )8-haloketones. This reaction has been most synthetically useful in intramolecular reactions. The following examples are illustrative. 

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