Enols sulfenylation

From intermediate 12, the path to periplanone B (1) is short but interesting. Enolization of 12 with lithium bis(trimethylsilyl)amide at -78 °C, followed by sulfenylation using Trost s reagent,12 affords a 16 1 mixture of regioisomeric monosulfenylated ketones favoring intermediate 17. The regioselectivity displayed in this reaction is... 

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

Asymmetric sulfenylation. In the presence of the chiral diamine (S)-l-methyl-2-(piperidinylmethyl)pyrrolidine (1), tin(II) enolates of ketones react with... 

N-Allenylazetidinone 181 rearranges to cephalosporin 182 in the presence of lithium chloride (Eq. 13.62) [70], This is a very unusual reaction that is presumed to be initiated by chloride ion-induced cleavage of the disulfide to give sulfenyl chloride 183. Thiolate attack at the allene sp carbon atom of 183 generates ester enolate 184, which cyclizes to 182. The reactivity of the allene function in 181 ensures the success of the reaction. 

Reaction of an enolate derived from piperazine-2,5-dione with an electrophilic sulfur species has been used to synthesize gliovictin and hyalo-dendrin. Thus, the enol (94) can be sulfenylated at low temperatures with sulfenyl chlorides in presence of triethylamine. A second thiomethyl group can be introduced at position 6 by reacting the enolate with dimethyldisul-fide as shown in Scheme 39. 

Ring expansion by chemistry discussed in the workbook gives 82 whose enolate is sulfenylated 83 and cyclised in acid solution with hydrolysis of the acetal to give 84 and the five-membered rings in 73 start to appear. 

Several medio are available for the intnxluction of sulfenyl groups a to carbonyl derivatives and these have been reviewed. - The most versatile procedure involves reaction of the enolate with an appropriate thiol derivative, but the preferred m od is largely dependent on the nature of the substrate employed (see below). In most instances, sulfur has been introduced in the divalent state and subsequently oxidized, although the oxidative step has been avoided by the direct introduction of sulfur at the S oxidation level. The oxidation of sulfides to sulfoxides is a trivial procedure that can be effected by a variety of reagents. Sodium metaperiodate, m-chloroperbenzoic acid and hydrogen peroxide are the most common oxidants, but r-butyl hydroperoxide, r-butyl hypochlorite, N-chlorobenzotriazole,... 

The sulfmylation of esters, - lactones, carboxylic acids, > amides and lactams may be effected by reacticm of the corresptHiding lithium enolates in THF at -78 to 0 C with dimethyl or difdie-nyl disulfides, or, less conunmily, with methyl or fdienyl sulfmyl halides. The enolates of ketones, however, are insufficioitly nucleq diilic to react with dialkyl sulfides unless HMPA is added to the re-acticm mixture, although they do react smoothly with diaryl sulfides. This difference allows the selective sulfenylation of esters in the presence of ketones (entry 5, Table 3). ... 

Because of their tendency to undergo aldol reactions, various conditions have been investigated to develop methods for the sulfenylation of aldehydes. Indirect methods involving metallation of the corresponding imines (10 Scheme 11 ) offer a preferred alternative to the low temperature direct sulfenylation described above, but better methods are still required. One possibility may Ite to exploit the rapid room temperature enolization of aldehydes observed on treatment with potassium hydride in THF. ... 

The sulfenylation of metalloimines is equally applicable to ketones, although using more reactive sulfur electrophiles it is possible to bring about reaction on the unmetallated enamine. ° Sulfenylation of ketone enol silyl ethers also proceeds well with the more reactive sulfur species. Sulfenamides and their derivatives e.g. 11) are particularly suited to the direct sulfenylation of ketones and active methylene compounds such as -diketones, -keto esters and malonates, which undergo facile reaction at room temperature (equation 5). This procedure, however, does not appear to have been exploited for the dehydrogenation of active methylene compounds icf. Section 2.2.4.1). By preparing the dianion (13)... 

Oxidation of Activated C—H Bonds Table 3 Sulfenylation of Lithium Enolates... 

Potassium enolates of aldehydes, Enolates of aldehydes are somewhat difficult to generate because of competing polymerization by base. They have been obtained recently in high yield by use of potassium hydride in THF at 0° and successfully alkylated, sulfenylated with diphenyl disulfide, and converted into o-iodo aldehydes by iodine. The last two reactions have not been observed previously. Sulfenylation of aldehydes has previously used indirectly generated lithium enolates and a reactive sulfenyl chloride. All three reactions are useful, however, for aldehydes with only one a-proton. Otherwise yields of monosubstituted aldehydes are low and largely by-products are obtained. 

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