Sulfides, alkyl synthesis

Epoxide Synthesis via Sulfide Alkylation/Deprotonation Procedure [51] (p. 360)... 

The same is true for a number of other allylic sulfur compounds in which the sulfur carries a lithium-coordinating heteroatom. Coordination encourages reaction next to sulfur (you might say it makes the lithium more at home there) and means that allyl sulfide alkylations can be made quite regioselective. The importance of this is probably not evident to you, but on p. 000 you will meet a synthesis of the natural product nuciferal in which this principle is used—the key step will be the alkylation of this allylic sulfide to give an 86% yield of the product with the alkyl group next to sulfur. 

Furukawa first reported a one-pot synthesis of epoxides using a reaction system composed of alkyl sulfides, alkyl halides, and aldehydes in the presence of solid KOH in MeCN (Scheme 1) [7]. Using chiral sulfide 1 enantiomerically enriched epoxides were obtained but with only moderate enantioselectivity and yield... 

Hydrobromic acid alkyl carbonate synthesis Carbonyl sulfide alkyl group source, long-chain Coconut acid alkyl halide mfg. 

Mercaptoacetic acid stirred 4 hrs. at 60° with slightly more than 2 moles 0-benzyl-N,N -dicyclohexylisourea in abs. dioxane benzyl 2-(benzylthio)-acetate. Y 84%. F. e. s. E. Vowinkel and C. Wolff, B. 107, 496 (1974) alkyl aryl sulfides s. Synthesis 1974, 430. 

Fumkawa and coworkers realized the first enantioselective substoichiometric epoxidation reaction of aldehydes via the sulfide alkylation/deprotonation route, based on their one-pot procedure for the synthesis of oxiranes using sulfides directly rather than the preformed sulfonium salts [6]. In the presence of 50mol% sulfide 1, which was prepared in three steps starting from (-l-)-camphorsulfonic acid, a 50% yield and 47% ee were obtained in the reaction of benzaldehyde with benzyl bromide under solid-liquid two-phase conditions (solid KOH/CH3CN). A catalyst turnover (TON = 2.3) was also observed when 10mol% catalyst was used in the reaction of 4-chlorobenzaldehyde (Scheme 20.3). The 0-methylated derivative of sulfide 1 gave the trows epoxides with an opposite configuration. 

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

Many 3-substituted indoles have also been prepared with the use of a-alkyl or a-aryl-p-keto sulfides. Thus indolization of aniline 5 with 3-methylthio-2-butanone 27 furnished indolenine 28, presumably via the same mechanism discussed earlier. The indolenine 28 was relatively unstable and reduced to the indole 29 without purification. Tetrahydrocarbazole 32 was prepared in 58% overall yield. Smith et al. made excellent use of the Gassman process in the total synthesis of (-i-)-paspalicine and (+)-paspalinine. ... 

Thiophenethiols are prepared by reduction of the sulfonyl chlorides or, more conveniently, by the reaction of Grignard rea-gents or thienyllithium compounds with sulfur. They have also been obtained by cleavage or thienyl alkyl sulfides with sodium in liquid ammonia. 3-Thiophenethiol is a by-product in the commercial thiophene synthesis. Thiophenethiols have recently also been prepared by a synthesis involving Friedel-Crafts reaction of 2,4-dinitrobenzenesulfenyl chloride with thiophenes, followed by basic cleavage of the resulting sulfide. ... 

Application of radical reactions to organic synthesis has recently received much atrendon, and various important reacdons have been discovered in this field. Alkyl halides, sulfides, seleniJes, and thiocarbonyl compounds have been used as precursors to alkyl radicals. Some examples are illustrated in Scheme 7.18. ... 

Treatment of a thiol with a base, such as NaH, gives the corresponding thiolate ion (RS-), which undergoes reaction with a primary or secondary alkyl halide to give a sulfide. The reaction occurs by an Sn2 mechanism, analogous to the Williamson synthesis of ethers (Section 18.2). Thiolate anions are among... 

Scheme 23. Barton s thiohydroxamate ester chemistry synthesis of alkyl pyridyl sulfides (127).

The Aggarwal group has used chiral sulfide 7, derived from camphorsulfonyl chloride, in asymmetric epoxidation [4]. Firstly, they prefonned the salt 8 from either the bromide or the alcohol, and then formed the ylide in the presence of a range of carbonyl compounds. This process proved effective for the synthesis of aryl-aryl, aryl-heteroaryl, aryl-alkyl, and aryl-vinyl epoxides (Table 1.2, Entries 1-5). 

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]. 

Most alkylthioquinoxalines (nuclear and extranuclear) have been made by primary synthesis (see Chapter 1), by alkanethiolysis of halogenoquinoxalines (see Sections 3.2.3 and 3.4.4), or by alkylation of quinoxalinethiones (see Section 5.1.2) the formation of a diquinoxalinyl sulfide during thiolysis of a halogenoqui-noxaline has been noted in Section 3.2.3. 

In 2008, Rykowski et al. reported the synthesis of optically active 2,2 -bipyridine alkyl sulfoxides by asymmetric oxidation of their corresponding readily accessible 2,2 -bipyridine alkyl sulfides. These sulfoxides were further evaluated as ligands for the enantioselective addition of ZnEt2 to benzaldehyde, providing only low enantioselectivities of up to 14% ee (Scheme 3.34). 

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