Synthesis of Allylic Sulfides

Finally, the application of S-allylic thiocarbamates to the synthesis of allylic sulfides and thiols was investigated (Scheme 2.1.4.20). 

Scheme 2.1.4.20 Synthesis of allylic sulfides from allylic thiocarbamates.

Diorganochakogenides. A method for synthesis of allyl sulfides and selenides involves formation of allylsamarium bromide and its reaction with PhX-XPh (X=S, Se) in THF. For a similar approach to benzyl sulfides, the benzylsamarium halides are formed in the presence of BiClj. Aqueous media can be used in this latter reaction. 

Trost BM, Scanlan TS. Synthesis of allyl sulfides via a palladium mediated allylation. Tetrahedron Lett. 1986 27 4141-4144. 

Gais H, Jagusch T, Spalthoff N, Gerhards F, Frank M, Raabe G. Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles asymmetric synthesis of allylic sulfides, allylic sulfones, and allylic alcohols. Chem. Eur. J. 2003 9 4202-A221. 

Asymmetric Synthesis of Allylic Sulfones and Allylic Sulfides and Kinetic Resolution of Allylic Esters... 

The Pd-catalyzed allylic alkylation of sulfinate ions, thiols, and thiocarboxylate ions with racemic cyclic and acyclic allylic esters in the presence of bisphosphane BPA generally provides for an efficient asymmetric synthesis of allylic sulfones, sulfides, and thioesters. The Pd-catalyzed rearrangements of allylic sulfinates and allylic O-thiocarbamates, both of which proceed very efficiently in the presence of BPA, are attractive alternative ways to the asymmetric synthesis of allylic sulfones and allyUc thioesters also starting from the corresponding racemic alcohols. 

We can illustrate the synthesis of allylic alcohols from allylic sulfoxides with this synthesis of the natural product nuciferal. We mentioned this route on p. 1257 because it makes use of a heterocyclic allyl sulfide to introduce an alkyl substituent regioselectively. The allyl sulfide is oxidized to the sulfoxide, which is converted to the rearranged allylic alcohol with diethylamine as the thiophile. Nuciferal is obtained by oxidizing the allylic alcohol to an aldehyde with manganese dioxide. 

Selective reduction of allyl sulfides implies that no scrambling of the carbon-carbon double bond occurs during the process. Effectively this has proved to be the case especially when lithium in ethylamine is used, and the method has allowed the regio- and stereo-selective synthesis of a large variety of 1,5-dienes including squalene (Scheme 25, entry a), mukapolide (Scheme 25, entry b), dendrolasin (Scheme 25, entry c), the basic nucleus of crassin acetate (Scheme 25, entry d) from 7,7-dialkylallyl sulfides and allyl halides, and also of 1,5-enynes " from propargyl sulfides and allyl halides (Scheme 34, entry b). 

Cohen has used a soluble version of the Simmons-Smith reagent to promote the 3,2-rearrangement of allylic sulfides (Scheme 52). He has also applied this methodology to the synthesis of sarkomycin (225). The allylic sulfide (221), easily available via a Petrow reaction, was first alkylated and the sulfo-nium ylide was then generated by a fluoride-promoted desilylation. Rearrangement of the ylide (223) gave the homoallylic sulfide (224) which was eventually transformed into sarkomycin (Scheme 53). 

P-Alkylation. The Michael-Arbuzov reaction of chloromethyl p-tolyl sulfide with trimethyl Phosphite or triethyl phosphite yields dimethyl- or diethylphosphonylmethyl p-tolyl sulfides, which are important intermediates for the synthesis of vinyl sulfides and sulfoxides, as well as for optically active derivatives of dimethylphosphonylmethyl p-tolyl sulfoxide (eq 7). This method of preparation of the chiral p-tolylthio monosulfoxide is complementary to the reaction using dimethylphosphonyl-methyllithium and (—)-(5)-menthyl p-toluenesulfinate in which the (+)-(7 isomer is obtained in high 3ueld and high optical purity (eq 8). The lithio dimethylphosphonylmethyl p-tolyl sulfoxide reacts with aldehydes and ketones to give the corresponding vinyl sulfoxides, which can be converted into optically active allylic alcohols (eq 9). ... 

The concentration of zinc accelerator-thiolate complexes in the rubber is not the only factor determining the balance of the two reactions in NR. Both the rate of desulfuration of polysulfide crosslinks and the rate of their thermal decomposition depend upon the positions of attachment of the sulfur chains to the backbone rubber chains and the detailed structure of the hydrocarbon at the ends of the crosslinks. In the course of normal accelerated vulcanization there are three different positions of attack on the polyisoprene backbone two of these are methylene groups in the main chain (labelled d and a in 3), and the third is the side chain methyl group (labelled b in 3). Direct analysis of the distribution of the sites of attack cannot yet be made on actual rubber vulcanizates, and information has had to be obtained solely by sulfuration of the model alkene 2-methyl-2-pentene and, more recently, 2,6-dimethyl-2,6-octadiene. The former (4) models the a-methylic site but only one of the two a-methylenic sites of polyisoprene the latter (5) models all three sites, but at the present time these are not all supported by the synthesis of relevant sulfides. Because allylic rearrangements are common in subsequent reactions of the sulfurated rubber, sulfur substituents appear not only on allylic carbon atoms but on isoallylic carbon atoms. Thus, from 2-methyl-2-pentene, the groups shown in Scheme 2 are formed. 

CHMO.. has been used in the diastereoselective oxidation of different p-hydroxy sulfides to the corresponding chiral p-hydroxy sulfoxides. Chiral p-hydroxy sulfoxides represent interesting compounds used as chiral auxiliaries in asymmetric synthesis, asymmetric ligands, or as building blocks for the synthesis of cyclic sulfides, benzoxathiepines, allylic alcohols, or leukotrienes [27]. The sulfoxidation of these substrates is a kinetic resolution, in which both the sulfide and the sulfoxide can be obtained in chiral form. Oxidation of the cyclohexyl derivative (Table 6.1, entry 2) by a semipurified preparation of in the presence of the enzymatic... 

Kondo T, Morisaki Y, Uenoyama S, Wada K, Mitsudo T. First ruthenium-catalyzed allylation of thiols enables the general synthesis of allyhc sulfides. J. Am. Chem. Soc. 1999 121 8657-8658. 

The synthesis of allyl sulfonamides by imidation of allyl sulfides with chloramine-T (TsNClNa) and subsequent [2,3]-sigmatropic rearrangement has been reported (Scheme 43). ... 

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

Allylic titanates having an electrofugal leaving group, e.g., trimethylsilyl68 75 - 77, at the 3-position are powerful reagents for the highly stereoselective synthesis of 1-hetero-substituted 3-alkadienes. For the carbonyl addition of the appropriate titanated allyl sulfides ( ) or carbamates ( and ), reliable y-selectivity and anti diastereoselectivity are reported. The... 

Depending on the choice of transfer agent, mono- or di-cnd-functional polymers may be produced. Addition-fragmentation transfer agents such as functional allyl sulfides (Scheme 7.16), benzyl ethers and macromonomers have application in this context (Section 6.2.3).212 216 The synthesis of PEG-block copolymers by making use of PEO functional allyl peroxides (and other transfer agents has been described by Businelli et al. Boutevin et al. have described the telomerization of unsaturated alcohols with mercaptoethanol or dithiols to produce telechelic diols in high yield. 

Oxidative phenolic coupling. Biosynthesis of the alkaloid narwedine (3) is known to involve oxidative phenolic coupling of norbelladine derivatives (1), but the usual oxidants for such coupling in vitro convert 1(R = H) into the oxomaritidine skeleton (4) rather than 3. A new biomimetic synthesis of 3 involves the palladacycle 2, formed by reaction of 1(R = CH3) with Li2PdCl4, which is known to form complexes with allylic amines or sulfides (8,176-177). Oxidation of 2 with thallium(III) trifluoroacetate effects the desired coupling to give 3. 

Snider and colleagues have developed the sequential ene reaction/thia-[2,3]-Wittig reaction which provide appropriately functionalized product 152 at allylic position on simple alkene 150 in two steps involving intermediate 151 (equation 87) . Thia-[2,3]-Wittig rearrangement was often utilized as a key step of natural product synthesis. Masaki and colleagues have demonstrated that the potassium enolate thia-[2,3]-rearrangement of aUyl sulfide 153 to 154 is useful for the synthesis of terpenoid diol component 155 of the pheromonal secretion of the queen butterfly (equation 88) . 

In their stereorational synthesis of (+)-[10.10] 61b, they reacted the epoxide 107 with a 1 1 3-butenylmagnesium bromide-cuprous iodide complex in dimethyl-sulfide-THF at low temperature. The predominant SN2 pathway gave the (+)-( )-allyl alcohol 108 whose Sharpless asymmetric epoxidation in dichloromethane at —23 °C for 10 min provided the corresponding epoxy alcohol and recovered (+)-(R)-allyl alcohol 108 (78 % yield and 95 % optical purity). The (R)-configuration was assigned following the Sharpless model61 for allylic alcohol epoxidation. 

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