Lactones selenenylation

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). 

Selenenylations of ketones, esters, lactones and lactams are usually effected by the reaction of the corresponding lithium enolates with PhSeCl, PhSeBr and PhSeSePh (with the exception of ketones) at low temperature. Aldehydes have not been selenenylated in this manner. Table 4 illustrates some typical products that have been made in this way. Selenenylation has been especially useful in natural piquet synthesis for the formation of a-methylenelactones from the parent a-methyl compounds (Scheme 15 and Table 4), and has significant advantages over the more traditional methods for ef-... 

A number of lactones have been selenenylated via their enolates, which are typically generated using lithium diisopropylamide (Table 1) a well-established procedure is available13. 

The selenenylation of a lactone enolate generated in situ by copper-mediated Michael addition to an a-methylene lactone affords stereoselectively the (phenylseleno)lactone 1814. 

Generation of seleno carboxylates occurs instantaneously on treatment of selenenyl halides with carboxylic acids and, consequently, the phenylseleno-lactonization of unsaturated carboxylic acids by phenylselenenyl chloride may be formally considered as intramolecular addition of phenylselenenyl carboxylate to the C-C double bond. The reaction of 4-cyclohep-tene-l-carboxylic acid with phenylselenenyl chloride to give lactone 40 is a good example. 

To a magnetically stirred solution of 152 mg (1.0 mmol) of 4-cyclooctene-1-carboxylic acid in 5 mL of CHjdj is added 110 mg (1.1 mmol) of F,t3N and the reaction mixture is kept at r.t. for short period. The solution is then cooled to —78 C and solid 212 mg (I.I mmol) of phenylselenenyl chloride is added in one portion. The reaction mixture is stirred at that temperature until completion which is indicated hy the full dissolution of the red-orange selenenyl chloride. The pale-yellow solution is then allowed to reach r.t., concentrated and chromatographed (silica gel, CH, CI2). Removal of the solvent from the appropriate fractions gives the six-membered lactone 42A as colorless crystals yield 94% mp 67 -69 °C. 

Quite recently, Tiecco [46a, 128] reported the asymmetric version of the one-pot conversion of, y-unsaturated esters and nitriles 261 (Scheme 42) into the enantiomerically enriched allylic ethers and alcohols 276 (Scheme 45). The reactions were effected with the selenenyl sulfate produced from the camphor diselenide 26. Unfortunately, in the present case, this diselenide must be employed in stoichiometric amounts. However, it can be partially recovered at the end of the reaction. Good chemical yields and enantiomeric excesses (up to 86%) were obtained in the methoxyselenenylation-elimination reactions. Lower ee was observed when the reactions were run in ethylene glycol or in water. In the case of the hydroxyselenenylations, reaction yields were low because the addition products 275 gave rise to the lactones, which were then deselenenylated to the butenolides. These were isolated in about 30% yield. 

The preparation of a-selenoketones, esters, nitriles and related compounds can easily be performed via alkylation of the corresponding enolates or stabilized carbanions [21]. These compounds have found many synthetic applications in radical chemistry. In Eq. (9), a typical example involving a ketone is depicted [22]. The stability of a-selenoketones such as 41 is remarkable. Similar reactions with lactones have been performed. For instance, this approach has been applied to the stereoselective synthesis of oxygen-containing rings to either faces of a bicyclic structure [23]. The approach based on a-selenenylation/radical allyla-tion compares favorably with classical enolate allylation procedures, which usually leads to mixture of mono- and diallylated compounds. Furthermore, this strategy is excellent for the preparation of quaternary carbon centers [24] as shown by the conversion of 43 to 45, a key intermediate for the synthesis of fredericamycin A, [Eq. (10)] [25]. Similar reactions with sulfoxides [26] and phosphonates [27] have also been reported. 

As exemplified by Scheme 15.35, the resulting selenenylated lactones can be easily converted into the corresponding alkenes and alkanes, by selenoxide syn-elimination and reductive deselenation, respectively [89 b, c]. 

Furanes. Grieco et al. have developed a general synthesis of 2,4- and 2,3,4-substituted furanes from substituted y-lactones, as illustrated for the conversion of (1), y-decalactone, into 2-hexyl-4-benzylfurane (5). The lactone enolate of (1) is alkylated to give (2). Selenenylation of the enolate of (2) with phenylselenenyl chloride leads to (3). Selenoxide fragmentation of (3) results almost... 

Selenoalkoxylation and -lactonization using chiral areneselenenyl derivatives such as 7 and 8, the ferrocenyl diselenide 9 , and the camphor-based species (10) are efficient processes. The diselenides are activated by Br to form reactive selenenyl bromides. 

---