Selenoxides reaction with ketones

Reaction with ketones. The reagent reacts with ketones in ether to introduce a C6H5SeCl2 group into the a-position. The products undergo selenoxide elimination to give a,0-enones they are reduced by thiourea to a-phenylseleno ketones. 

Selenenyl halides are relatively stable, though moisture sensitive, compounds that are generally prepared by the reactions shown in Scheme 7 and behave as electrophihc selenium species. " They react with ketones and aldehydes via their enols or enolates to afford a-seleno derivatives (e.g. (17) in equation 11). Similar a-selenenylations of /3-dicarbonyl compounds, esters, and lactones can be performed, although the latter two types of compounds require prior formation of their enolates. Moreover, the a-selenenylation of anions stabilized by nitrile, nifro, sulfone, or various types of phosphorus substituents has also been reported (equation 12). In many such cases, the selenenylation step is followed by oxidation to the selenoxide and spontaneous syn elimination to provide a convenient method for the preparation of the corresponding a ,/3-unsaturated compound (e.g. 18 in equation 11). Enones react with benzeneselenenyl chloride (PhSeCl) and pyridine to afford a-phenylselenoenones (equation 13). 

Schemes 51-54) - (xiii) a-metallovinyl selenoxides (Scheme 179) (xiv) a-metalloalkyl selenones (Schemes 55 and 56) i29,i30,i38,206 gjjjj v) a-selenometalloenolates derived from esters (Scheme 10), lactones (Scheme 38), lactams - including B-lactams (Scheme 42, a Scheme 99), and nitroalkanes (Scheme 41). Most of the organometallics listed produce the corresponding alcohols by reaction with aldehydes and ketones and further hydrolysis of the resulting alcoholates. 

P-Hydroxy selenides are conveniently prepared from epoxides by treatment with sodium phenylse-lenide (Scheme 32) and by the addition of benzeneselenenic acid and its derivatives to alkenes (Scheme 33), - -" although in some cases these reactions are not regioselective. Useful phenylseleno -etherification and -lactonization reactions have been developed which can be regioselective (equation 42 and Schemes 34 and 35). -" " Selenide- and selenoxide-stabilized carbanions have been used in addition reactions with aldehydes and ketones, - and the reduction of a-seleno ketones also provides a route to P-hydroxy selenides. ... 

The pyrolysis of selenoxides takes place at room temperature or below. In the presence of a p-hydrogen, a selenite will give an elimination reaction after oxidation to leave behind an alkene and a selenenic acid (Scheme 6.22). Oxidizing agents such as hydrogen peroxide, ozone, or m-CPBA are quite often used. This reaction type is commonly used with ketones leading to the formation of enones. 

Conjugate addition of phenyl trimethylsilyl selenide to a,/3-unsaturated aldehydes and ketones has been attained by using triphenylphosphine, zinc chloride, or trimethylsilyl trifluoro-methanesulfonate as the catalyst. Combination of this reaction with selenoxide elimination provides a one-pot procedure for a-alkoxyalkylation of a,/3-unsaturated ketones (eq 3). 

Selenides eliminate readily without a base. They are generally prepared from enolate anions by reaction with diphenyldiselenide or phenylselenyl bromide to give phenylselenides. The phenylselenides are oxidized with sodium periodate, hydrogen peroxide, or peracids to the selenoxides, which eliminate even at room temperature to afford the a,p-unsamrated ketones and esters [107]. 

Iodine-catalysed hydroperoxidation of cyclic and acyclic ketones with aqueous hydrogen peroxide in acetonitrile is an efficient and eco-friendly method for the synthesis of gem -dihydroperoxides and the reaction is conducted in a neutral medium with a readily available low-cost oxidant and catalyst.218 Aryl benzyl selenoxides, particularly benzyl 3,5-bis(trifluoromethyl)phenyl selenoxide, are excellent catalysts for the epoxidation of alkenes and Baeyer-Villiger oxidation of aldehydes and ketones with hydrogen peroxide.219 Efficient, eco-friendly, and selective oxidation of secondary alcohols is achieved with hydrogen peroxide using aqueous hydrogen bromide as a catalyst. Other peroxides such as i-butyl hydroperoxide (TBHP), sodium... 

The selenium version of this reaction offers the advantages that over-oxidation is no problem and that the elimination of the selenoxides occurs at room temperature or below so that the oxidation and elimination normally occur as a single step.23 A simple example is the preparation of another starting material 158 for a dienone-phenol rearrangement.24 The lithium enolate of spirocyclic ketone 155 reacts with PhSeCl to give 156 and oxidation with H202 gives the dienone 158 directly, with the selenoxide 157 as an intermediate. The overall yield is 83%. 

The treatment of a,p-unsaturated ketones with organocopper reagents provides another method to access specific enolates of unsymmetrical ketones. Lithium dialkylcuprates (see Section 1.2.1) are used most commonly and the resulting enolate species can be trapped with different electrophiles to give a,p-dialkylated ketones (1.27). Some problems with this approach include the potential for the intermediate enolate to isomerize and the formation of mixtures of stereoisomers of the dialkylated product. The intermediate enolate can be trapped as the silyl enol ether and then regenerated under conditions suitable for the subsequent alkylation. Reaction of the enolate with phenylselenyl bromide gives the a-phenylseleno-ketone 12, from which the p-alkyl-a,p-unsaturated ketone can be obtained by oxidation and selenoxide elimination (1.28). 

Conversion of ketones into a,(3-unsaturated ketones has been effected by bromination-dehydrobromination, although a better method involves a-phenyl-seleno ketones as intermediates. These are normally obtained by reaction of the enolate of the ketone with a phenylselenyl halide or diphenyl diselenide at low temperature. Oxidation with hydrogen peroxide, sodium periodate or other oxidant gives the selenoxide which immediately undergoes syn p-elimination to form the a, -unsaturated ketone. The process is tolerant of many functional groups, such as... 

Arylthallium bis(trifluoroacetate)s are converted by successive treatment with KF and BF3 into aryl fluorides.Thallium(iii) nitrate (TTN) readily oxidizes dialkyl sulphides and selenides to the corresponding sulphoxides or selenoxides, and 2-(alkylthio)-l-arylethanones (37) into compounds (38) in methanolic solution.In a modification of the TTN oxidative conversion of aryl alkyl ketones into arylacetic acids, enol ethers derived from the ketones are used instead of the ketones themselves. This reduces the formation of side products. Cyclic aralkyl ketones (39) may be ring-expanded and alkylated to give compounds (40) via treatment of their Wittig-derived alkenes with TTN/ an extrapolation of the basic reaction discovered previously. 

Reich has now described the ready preparation of a-lithio-selenides and -selenoxides, which smoothly condense with aldehydes and ketones. The resultant /3-hydroxy-selenides and -selenoxides can be reductively eliminated under very mild conditions to give tetrasubstituted olefins, which are not readily available from the Wittig reaction. The /3-hydroxyselenides can be converted into olefins under milder conditions than their sulphur equivalents, using methane-sulphonyl chloride in triethylamine. 

---