Epoxides, sulfinyl

Optically active allylic alcohols can only be prepared from optically active sulfinyl epoxides when the created double bond is conjugated to an aromatic system. One example is described below29. 

The reaction of sulfinyloxirane 130 with n-C4H9Li takes place at the sulfinyl group to afford the desulfinated epoxide 133 in good yield. This reaction proceeds at — 100°C with concomitant formation of phenyl n-butyl sulfoxide 132. Thus, oxiranyllithium 131 picks up the acidic proton of the in situ formed 132 to generate the reduce epoxide 133 (equation 46) . 

Takatsuki and co-workers have recently introduced the 3, 5 -0-sulfinyl group which has the dual purpose of protection and activation in nucleoside chemistry. For example, compound 13, prepared by protection of 12 as shown in Scheme 3, underwent reaction with benzyl isocyanate followed by intramolecular displacement of the sulfmate to give the product 14 <2004TL137>. A similar approach has also been used to prepare thioglycoside epoxides <2004CAR2895>. 

Many other uses of a-sulfinyl carbanions are found in the literature, and in the recent past the trend has been to take advantage of the chirality of the sulfoxide group in asymmetric synthesis. Various ways of preparation of enantiopure sulfoxides have been devised (see Section 2.6.2) the carbanions derived from these compounds were added to carbonyl compounds, nitriles, imines or Michael acceptors to yield, ultimately, with high e.e. values, optically active alcohols, amines, ethers, epoxides, lactones, after elimination at an appropriate stage of the sulfoxide group. Such an elimination could be achieved by pyrolysis, Raney nickel or nickel boride desulfurization, reduction, or displacement of the C-S bond, as in the lactone synthesis reported by Casey [388]. 

Ferrocene is best deprotonated by r-BuLi/r-BuOK in THF at 0 °C,360 since BuLi alone will not lithiate ferrocene in the absence of TMEDA and leads to multiple lithiation in the presence of TMEDA. In the example below,216 a sulfur electrophile and a Kagan-Sharpless epoxidation lead to the enantiomerically pure sulfinyl ferrocene 398. The sulfinyl group directs stereoselective ortholithiation (see section 2.3.2.2), allowing the formation of products such as 399. Nucleophilic attack at sulfur is avoided by using triisopropylphenyllithium for this lithiation. 

Pradilla et al. have shown that simple p-tolyl vinyl sulfoxides undergo nucleophilic epoxidation with metal alkyl peroxides to give enantiopure sulfinyl oxiranes.138 This process takes place with fair to excellent diastereoselectivities. The same group recently reported the epoxidation of diastereomeric hydroxy vinyl sulfoxides, bearing an additional stereocenter adjacent to the reactive carbon-carbon double bond. Hydroxy vinyl sulfoxides 256 and 258 underwent epoxidation with lithium ferf-butyl peroxide with high anti selectivity. However, when potassium ferf-butyl peroxide was used, only hydroxy vinyl sulfoxide 256 showed anti... 

For the epoxidation of y-oxygenated vinyl sulfoxides 260 and 262, with sodium terf-butyl peroxide, an even greater reversal in stereoselectivity was observed. Epoxidation of260 gave the anti isomer 261, whereas 262 gave the syn isomer 263 (Scheme 67).139 This remarkable reversal of facial selectivity may be understood in terms of a mismatched situation and underlines that a chiral sulfinyl functionality is an extremely powerful chiral controller. 

In conjunction with work in natural products synthesis, the controlled installation of stereocenters alpha to indole C2 remains of significant interest. In their approach to Clausena alkaloids, e.g., (-)-(5R, 6S)-balasubramide, Wang and co-workers employed an intramolecular 8-CMc/o-epoxide-arene cyclization for installation of a C2-C3 8-membered lactam moiety with excellent enantioselectivity <07OL1387>. The Chen group has reported a diastereoselective reaction between 2-lithioindoles and chiral A -terf-but ane sulfinyl... 

Asymmetric induction occurs during the alkylation of ketones with the a-sulfinyl carbanion derived from optically active 1-chloroalkyl-p-tolyl sulfoxides (equation 18). The resulting chloro alcohol may be converted to an optically active epoxide under alk ine conditions and the sulfinyl group is removed with n-butyllithium. While the process benefits from high asymmetric induction in the alkylatitm reaction, it must be recognized that, when either R 91H and/or R R diasteretHnerk compounds are formed and require separation. 

Methyl chloroacetate reacts with the anion of (7 )-methyl p-tolyl sulfoxide to give the corresponding 8-chloro-p-keto sulfoxide (eq 10), which can be easily transformed into the corresponding 3-hydroxy sulfoxide which gives, in presence of a base, the optically active a-sulfinyl epoxides. As illustrated here, a-sulfinyl epoxides can be opened by cuprates, leading to chiral homoallylic alcohols. ... 

The reactions between a-metalloalkyl sulfoxides and electrophiles have been extensively studied. Although alkylations of the sodium or potassium salts of dialkyl sulfoxides are not always very efficient since a,a -dialkylated sulfoxides are often produced (or stilbene in the case of methyl-sulfinyl carbanion and benzyl bromide ), those employing the lithioalkyl aryl sulfoxides work more efficiently with alkyl or allyl halides " and with epoxides. " " Typical examples of these alkylations, allylations and hydroxyalkylations (from epoxides) are illustrated in Scheme 86. 

Sulfonyl carbanions are even more stable than sulfinyl carbanions and are consequently of greater significance in synthesis. They can be alkylated and acylated at the a-carbon atom using organolithium bases, and cyclic sulfones can be formed by intramolecular alkylation, (see Chapter 10, p. 202). Sulfonyl carbanions (73) also react with terminal epoxides, and this reaction is applicable for the synthesis of unsaturated alcohols (74) (Scheme 33). 

Nitrobenzenesulfonyl peroxy (A) or sulfinylperoxy (B) intermediates (Figure 6), generated at low temperature from 2-nitrobenzenesulfonyl- or -sulfinyl chloride with K02, serve as excellent oxidizing agents and preferentially epoxidize isolated double bonds rather than enones [Pg.138]

In spite of the CIDNP polarization pattern, we believe the sulfinyl mechanism can be dismissed. First, the SO bond in a sulfinyl radical is very strong. Using Benson s estimate for the heat of formation of the phenylsulfinyl radical (13 kcal/mol) [63] and standard values for the other relevant compounds [98], the S-0 bond energy is ca. 102 kcal/mol, whereas the C-S bond is some 35 kcal/mol weaker. Transfer of an O atom from phenylsulfinyl to a methyl radical is endothermic by 11 kcal/mol, and to epoxidize ethylene endothermic by 40 kcal/mol. (The relevance of the latter example will become clear below.) Furthermore, from the a-cleavage work discussed previously, it is clear that the expected product from reaction to an arylsulfmyl radical and a carbon radical is a sulfenic ester or disproportionation product. 

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