Sulfinate esters, synthesis

With regard to the sulfmyl chlorides needed for sulfinate ester synthesis, a large number of them are readily accessible by oxidation of the corresponding disulfide according to the Young and Herrmann procedure."4 However, in the case of the more hindered ferf-butyl chloride, Netscher and Prinzbach s method gives better... 

The results of Table 22 prove unambiguously that the stereochemical outcome of sulfinate ester synthesis is highly dependent on the base used, and that we are dealing with a general stereochemical behavior in the asymmetric synthesis of sulfinate esters. 

Schneider and Simon82 prepared / -ketosulfoxides 47a and 47b by sulfinylation of the dianions of the methyl acetoacetates 48a and 48b with sulfinate ester 19 followed by decarboxylation of the intermediate products (Scheme 2). Apparently this avoids racemiz-ation experienced by others in the direct synthesis of these compounds9. /J-Ketosulfoxides are also available from the reaction of the anion derived from methyl p-tolyl sulfoxide with esters (see Section II.E). They can also be obtained, in some cases, through the hydrolysis of a-sulfinylhydrazones whose synthesis is described below. Mention has already been made of the synthesis of 2-p-tolylsulfinylcycloalkanones such as 32. 

The lithium enolate of ethyl V-methoxyacetimidate (55) was also successfully sulfmy-lated by treatment with sulfinate ester 19 (equation 19)87. Sulfoxide 56 was used in an asymmetric synthesis of some /1-hydroxy esters. 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

Alkenyl sulfoxides (42 and 43) were first prepared in optically active form by Mulvaney and Ottaviani , described in an article overlooked by most workers in the field, and a year later by Stirling and coworkers through the reaction of the appropriate vinyl Grignard reagent with sulfinate ester 19. Both groups studied the addition of nucleophiles to the carbon-carbon double bond . More recently, Posner and coworkers reported a similar synthesis of ( )-l-alkenyl sulfoxides, e.g. 44 and In the synthesis of 45,... 

Active methylene compounds may be sulfinylated by reaction of their enolate anions with sulfinate ester . This reaction has been investigated much in recent years and the compounds resulting from it have been of considerable use in asymmetric synthesis (see the chapter by Posner). Examples of the sulfinylation are given in the following paragraphs. 

The stereospecific conversion of sulfinates into sulfoxides of known chirality has been applied as a general method for determining the absolute configuration of a wide range of optically active sulfinic esters. For example, the absolute configurations of a series of alkyl alkanesulfinates obtained by asymmetric synthesis (107) or resolution via 3-cyclodextrin inclusion complexes (106) were determined by this method. 

This procedure affords a one-step synthesis of aromatic sul-finic esters from readily available starting materials. It is successful with a variety of types of aromatic sulfinic esters.6 The method is rather unattractive for aliphatic disulfides, however, because the nature of by-products formed makes rigorous purification of the sulfinic esters impracticable.8... 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

Disulfides, diselenides, and ditellurides can be oxidized by hypervalent iodine compounds quite easily. Depending on the reaction conditions disulfides can be oxidized to sulfinic esters [59] or thiosulfonic S-esters [60,61]. Diselenides can be transformed into selenosulfonates [62]. Arenetellurinic mixed anhydrides are mild oxidants and can be obtained by oxidation of the corresponding ditellurides as shown in Scheme 9 [63]. Recently it was shown that a thioacetal based linker for solid-phase synthesis can be cleaved oxidatively using [bis(trifluoro-acetoxy)iodo]benzene 4 [64]. 

A similar synthesis of enantiopure (l )-sulfinamides 123 from indane-derived toluenesulfonyl 1,2,3-oxathiazolidine-2-oxide 121 has been developed. This method includes chemoselective ring opening with inversion of configuration at the sulfur atom, using Grignard reagent at the first step and lithium amide in liquid ammonia in the second step (Scheme 17) <2002JA7880>. Intermediate stable and crystalline sulfinate esters 122 were isolated in >95% yield in diastereopure form. 

The seminal work of Solladid on the epimerization of sulfinate esters 50 and 51 in acidic medium in order to displace the equilibrium by precipitation of the less soluble isomer 51, permitting its isolation in 80-90% yield,84 constitutes a real breakthrough in the synthesis of sulfoxides (Scheme 14). 

This is the second important contribution of Kagan s group in the synthesis of chiral sulfoxides. The method was reported in 1989 for the synthesis of tert-butyl sulfoxides,90 and the full paper on the generalization of the method was published in 1991.86 The approach is based on the synthesis and use of an o.p. cyclic sulfite in the synthesis of various sulfoxides by two successive condensations of two organometallic reagents, RjM and R2M. Thus, the sulfoxides are produced in three separate steps the formation of cyclic sulfite, synthesis of sulfinate esters, and transformation of sulfinates to chiral sulfoxides. 

The reaction of 60 with an excess of alkane- or arenesulfinyl chloride affords sulfinate esters 61-(R) and 61-fSj in good yields and moderate selectivity [(4-10) 1]. The diastereomeric sulfinates were separated either by crystallization or by column chromatography. Two arene- and two alkanesulfinates were prepared optically pure by the reported method (Scheme 18). The major isomer of the methanesulfinate was used in the synthesis of o.p. (R) methyl p-tolyl sulfoxide 62 in 76% yield, while the p-toluenesulfinate was used to obtain the (S)-p-phenoxyphenyl p-tolyl sulfoxide 63 in 70% yield. 

In order to get better stereochemical control and to circumvent the use of sulfinyl chlorides in the synthesis of sulfinate esters, the reaction of chlorosulfite esters of... 

Moreover, N-sulfinyl oxazolidinones have been shown to be good intermediates for the synthesis of chiral sulfinate esters and sulfinamides with excellent ee. In all cases, the absolute configuration of the sulfoxide obtained is in agreement with the fact that nucleophilic displacement occurs with inversion of configuration at the sulfur center in the starting /V-sulfinyl oxazolidinone. 

The first parameter to optimize was the nature of the base used. While there were precedents in the literature for the change in the starting chiral alcohol, to the best of our knowledge there was no report on the effect of the base on the stereocourse of the formation of sulfmate esters. In the literature on the asymmetric synthesis of sulfinate esters, statements such as asymmetric synthesis of sulfinate esters is achieved by the reaction of sulfmyl chloride with a chiral secondary alcohol in the... 

Sulfoxides of type R R2SO and sulfinic esters such as R S(0)0R2 have been isolated as stable enantiomers and the latter are useful in synthesis. 

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