Sulfinyl compounds

Resolution of various racemic P-chiral phosphorylacetates 70 involved the same approach as was shown for sulfinylcarboxylates (Scheme 2). However, unlike the case of sulfinyl compounds, only PEE proved efficient for their P(0) analogues. 

Table 11 summarizes the relative conformation stabilities of various sulfinyl carbanions, based on the H/D exchange rates of the corresponding sulfinyl compounds 36-39. The results are in good agreement with the order of stabilities obtained from the MO calculations using the 3-21G basis set. This is remarkable, since the calculation did not take into consideration the solvent effect, despite the strong unsymmetrical solvation on the a-sulfinyl carbanion. 

The chemistry and reactions of /V-sulfinyl compounds have been summarized in two reviews appearing in the late 1960s and early 1970s.75 There is also a short article in a recent comprehensive text.76... 

Usually, N-sulfinyl compounds (59) behave as thionyl transfer reagents, similar to, but milder than, thionyl chloride. For example, o-diamines with A-sulfinylbenzeneamine (59 R = Ph) afford fused 1,2,5-thiadiazoles, as in Scheme 8a.77 The advantage of using Af-sulfinyl compounds, rather than thionyl chloride itself, is that concomitant chlorinations and oxidations are avoided. This is of particular importance in the synthesis of 2,1-benzisothia-zoles (Section V,B,6). Singerman s reagent, N-sulfinylmethanesulfonamide (60) is especially valuable 78 it was used very successfully in the synthesis of a series of benzobis(isothiazoles).79... 

There have been some reports of the use of N-sulfinyl compounds to transfer both a nitrogen and a sulfur atom. An example is the reaction of N-sulfinylcyclohexylamine (59 R = cyclohexyl) with diphenylcyclopropenone in the presence of nickel tetracarbonyl. An isothiazolinone S-oxide (62) was the product.80 Similarly, A-sulfinyl-/>-toluenesulfonamide (59 R = tosyl) and the Wittig reagent triphenylphosphonium phenylbenzoylmethylide give 1,2,3-thiadiazoline (63).8 ... 

The unsaturated sulfinyl compound 105 can be converted into the iodooxathiane 107 either directly by AModosuccinimide or via the sulfoxide 106, providing the first example of an iodonium-promoted Pummerer rearrangement <00H(52)465>. 

A different approach to the resolution of sulfoxides was recently reported by MikcJajczyk and Drabowicz (35). It takes advantage of the fact that sulfoxides as well as other sulfinyl compounds ry easily form inclusion complexes with 3-cyclodextrin. Since -cycl dextrin (the host) is chiral, its inclusion complexes with racemic guest substances are mixtures of diastereomeis that can be formed in unequal amounts. In this way a series of alkyl phenyl, alkyl p-tolyl, and alkyl benzyl sulfoxides has been resolved. However, the optical... 

All the chiral sulfinyl compounds discussed above are the derivatives of achiral sulflnic acid 94a. Another class of chiral sulfinyl compounds may be derived from achiral sulfurous acid 94b via replacement of the hydroxy groups by suitable substituents. A brief survey of such chiral sulfinyl compounds is presented next. 

NMR spectroscopy was found to be a valuable technique for differentiation between the enantiomers of optically active compounds. The principles of the methods used to distinguish between enantiomers by means of NMR have been developed and reviewed by Mis-low and Raban (217). The best results from the point of view of the determination of optical purity and absolute configuration of chiral sulfur compounds, especially of sulfinyl compounds, have been obtained with the help of chiral solvents (218). Pirkle (86) was the first to demonstrate that enantiomeric sulfoxides have nonidentical NMR spectra when dissolved in chiral alcohols having the following general formula ... 

The polarimetric method, in combination with the results of chemical correlation, made it possible to determine the optical purity of a range of chiral sulftnates (105-107), thiosulfinates (35,105), and sulfinamides (83) with the sulfur atom as a sole center of chirality. These compounds were converted by means of Grignard or alkyl-lithium reagents into sulfoxides of known specific rotations. This approach to the determination of optical purity of chiral sulfinyl compounds has at least two limitations. The first is that it cannot be applied to sterically hindered compounds [e.g., t-butyl /-butanethio-sulfinate 72 does not react with Grignard reagents]. Second, this... 

The structure of A -sulfinyl compound 39 was solved using a single crystal grown by the slow evaporation of a solution of dichloromethane (DCM) and hexane (Figure 7) <2003T4651>. The A -sulfinyl compound crystallizes with two molecules in a unit cell. This work provides additional evidence for the (Z)-preference of this dienophile used in [4-1-2] cycloaddition reactions to prepare 1,2-thiazines. 

Application of electron impact ionization mass spectrometry (EI-MS) techniques for the analysis of 1,2-thiazines has waned since the publication of CHEC-II(1996). In one recent example of this technique, bicycle 44 was ionized at 70 eV and 180°C to afford radical cation 53, 54 via loss of CO2, and W-sulfinyl compound 55 and 1,3-cyclohexa-diene radical cation 56 via a retro-[44-2] reaction in the gas phase (Scheme 5) <2002TA2407>. 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

A general overview for the formation of optically active sulfinylated compounds from menthyl (S)-4-methylbenzenesulfinate can be gained from the literature13-14-18-26. 

The Pummerer reaction of sulfinyl compounds involves the formation of an a-functionalized sulfide [244, 245] from a sulfoxide. Acetic anhydride is commonly used as the electrophile, which adds to the sulfoxide to yield a sulfonium salt, and the rearrangement occurs through successive formations of an ylide (rate-determining step) and an alkylidene sulfonium, trapped by a nucleophile, or stabilized by a proton loss with formation of a vinyl sulfide. 

Slemon and Macel [13] used several intermediates for the preparation of omeprazole. The drug was produced from the corresponding acetamide-sulfide compounds by a process of oxidation to form the amide sulfinyl compound, followed by alkaline hydrolysis to the sulfinyl carboxylate or salt, and decarboxylation. The methods are as follows ... 

A Pummerer rearrangement features in two approaches to 1,3-oxathiins. Refluxing y,8-unsaturated sulfinyl compounds (26) in xylene containing TsOH effects conversion to the 3,1-benzoxathiin (27) via a sulfonium ion intermediate (95CC1197), whilst 2-(hydroxymethyl)phenyl sulfoxides (28), readily cyclise to the benzoxathiin (95T6819). 

The action of SOCl2 on o-aminothiophenols leads to 1,2,3-benzodithiazolylium salts (4), presumably via the sulfinyl compounds (82) (65JOC2763). In an analogous reaction, the p-tosylamide of o-aminophenol is converted into the 1,2,3-benzoxathiazoline (198). 

The hetero-DielsAlder reaction of A-sulfinyl 141 (X = 0 or NR) or thionitrosoarene 144 dienophiles with dienes 142 is the main method for the formation of 3,6-dihydro-2//-l,2-thiazine 1-oxides 143 or 3,6-dihydro-2//-1,2-thiazines 145 (Scheme 73) . The mechanistic and stereochemical aspects of this reaction are covered in detail in GHEC-II . In general, thionitrosoarenes 144 are transient in nature, rather difficult to prepare, and thus have a limited role in the synthesis of 1,2-thiazines. On the other hand, A-sulfinyl compounds 141 and related sulfur diimines are more stable and are isolable species. The common method of preparation of the A-sulfinyl compounds involves treatment of an amine or amide with SOCl2 and base. 

Asymmetric [4 + 2] cycloaddition reactions of A-sulfinyl compounds and dienes have been developed <2002TA2407, 2000TL3743>. Excellent enantioselectivity is observed for the preparation of product 148 by the reaction of A-sulfinyl dienophiles 146 and acyclic diene 147 catalyzed with Cu(II) and Zn(II) complexes of Evans bis(oxazolidinone) ligands (Scheme 74) <2004JOC7198>. 

Neil E. Schore Reduction with Oiimide Daniel J. Pasto, Richard T. Taylor The Pummerer Reaction of Sulfinyl Compounds Qttonno DeLucchi, Umberto Miotti, Giorgio Modena... 

Two general classes of V-sulfinyl compounds have been employed as dienophiles. The most widely utilized type are N-sulfinyl species (115), formally monoimines of sulfur dioxide, which produce 3,6-di-hydrothiazine 1-oxides (116) (Scheme 14) upon cycloaddition. - -phe analogous bis-imines of sulfur dioxide (117) have also been used upon occasion as dienophiles to yield the 3,6-dihydrothiazine 1-imines (118). Both processes show excellent regioselectivity and are syn stereoselective with respect to the... 

As noted above, the stereochemical outcome at sulfur in these cycloadditions is not yet understood. Relatively few systems, particularly among the older examples, have been well characterized with respect to sulfur stereochemistry and thus existing data are sparse. Moreover, although N-sulfinyl compounds prefer to exist as the (Z)-isomers, it is not clear if they always undergo cycloaddition in this geometrical form. It is also known that the Diels-Alder reactions of N-sulfinyl compounds are sometimes reversible, which complicates the issue. ... 

One other example of an intramolecular -sulfinyl carbamate cycloaddition is depicted in Scheme 17. In this case, diene carbamate (133) was converted to a sulfinyl compound which cyclized to give exclusively adduct (135). It was suggested that the cycloaddition occurs via an endo boat-like iV-sulfinyl carbamate conformation (134). The alternate endo chair-like conformation (137) leading to isomeric adduct (138) is destabilized relative to (134) due to an eclipsing interaction between Ha and Hb. Adduct (135) was converted to amino sugar (136) in a few steps. 

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