Sulfoxides, unsaturated

Although a,/J-unsaturated sulfoxides are easily prepared (see Section D.1.1.1.5.), they arc usually obtained as a mixture of E- and Z-isomers11 both of which may be deprotonated by... 

In this chapter the addition of carbon nucleophiles to simple a,j8-unsaturated sulfoxides, a-sulfinyl-a,/ -unsaturated ketones and a-sulfmyl-a,/ -unsaturated lactones will be discussed separately, in most cases the asymmetric induction arises from the chirality at sulfur. 

The stereochemical outcome and the diastereoselectivity of the addition of the anion of diethyl propanedioate to a,/ -unsaturated sulfoxides is dependent on the reaction solvent, the metal counterion and the geometry of the a,/ -unsaturated sulfoxide1 - 3. 

The addition of enolate anions to (E)- and (Z)-3,3,3-trifluoro-l-[(4-methylphenyl)sulfinyl]-1 -propene has been investigated (E)- and (Z)-a,/(-unsaturated sulfoxides undergo addition in the opposite stereochemical sense3,4. In general, yields and product diastereoselection are high. When the -position of the double bond of the enolate is substituted then all four diastereomer-ic products result. 

Isomeric (E)- and (Z)-a,/f-unsaturated sulfoxides undergo addition with opposite dia-stereoselectivities. 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

The Michael addition of nucleophiles to a,/J-unsaturated sulfoxides creates initially a-sulfmyl carbanions by nucleophilic attack on the /J-carbon atom. Russell and Becker157 found that treatment of a mixture of diphenylmethane and anisaldehyde with potassium t-butoxide in DMSO gave at first the condensation product 170, which upon Michael addition afforded the final product 171. 

Abbott and coworkers229 found that nucleophilic addition of amines to a, p-unsaturated sulfoxide gave asymmetrically induced adducts. For example, treatment of (R)-(—)-cis-propenyl p-tolyl sulfoxide 184 with piperidine in methanol gave a quantitative mixture of the diastereomeric adduct 185. Reduction of this mixture gave (Rs)-(Sc)-2-piperidinopropyl p-tolyl sulfide 186 in 74% optical yield, suggesting that the amines attack from the opposite side of the bulky aryl group at the transition state, as shown above (Figure 6). 

Asymmetric synthesis using a-sulfinyl carbanions and / -unsaturated sulfoxides... 

Arai Y., Koizumi T. Synthesis and Asymmetric Diels-Alder Reactions of Chiral. Alpha.,.Beta.-Unsaturated Sulfoxides Bearing a 2-Exo-Hydroxy-lO-Bornyl Group As an Efficient Ligand on the Sulfur Center Rev. Heteroat. Chem. 1992 6 202-217 Keywords allenic sulfoxide, a-sulfinylmaleate, a-sulfinylmaleimide, asymmetric synthesis, chiral unsaturated sulfoxides... 

In the presence of Znl2 in acetonitrile the saturated sulfoxide 1262 is converted by the O-trimefhylsilylketene acetal 663 into the sulfide 1263 in 55% yield and HMDSO 7 [54] whereas the unsaturated sulfoxide 1264 affords with excess O-silyl-ketene acetal 663 the bis-addition product 1265 in 45% yield [55, 56] (Scheme 8.22). 

P, y-Unsaturated sulfoxides (e.g. 3-thiene oxides) can be prepared by trapping of the in Situ-generated 349 with dienes in a Diels-Alder-type reaction (equation 127) . 

Corey and Chaykovsky found that the dimsyl anion reacts with benzophenone and benzaldehyde to afford the corresponding 9-hydroxysulfoxides 109 and 110. Thermal decomposition of these jS-hydroxysulfoxides was shown to give a, -unsaturated sulfoxides or olefins . Thus, the reaction of dimsyl anion with benzophenone at 100 °C gave 1,1-diphenylethylene, diphenylmethane, 1,1-diphenylcyclopropane and diphenylacetaldehyde, besides 1, l-diphenyl-2-methylthioethylene . 

Treatment of a-dichloromethyl phenyl sulfoxide with lithium diisopropylamide in THF gave monolithiated derivative 122, which upon further treatment with aldehyde afforded the )S-hydroxy-a-dichlorosulfoxide 123. Thermolysis of 123 gave dichloroketone 124, by extruding benzenesulfenic acid as shown below . Similarly, in the reaction of lithio-a-fluoromethyl phenyl sulfoxide and aldehyde, fluoromethyl ketone 126 was obtained, after thermolysis of the hydroxy intermediate 125. Diethylphosphorylmethyl methyl sulfoxide was shown by Miko/ajczyk and coworkers to be lithiated with n-BuLi to intermediate 127, which upon treatment with carbonyl compounds afforded the corresponding a, -unsaturated sulfoxides 128 in good yields. 

This chapter, however, does not deal with above-mentioned reactions of sulfoxides. Rather it is limited to asymmetric synthesis using a-sulfinyl carbanions and -unsaturated sulfoxides, specifically in which the stereogenic sulfoxide sulfur atom is enantiomerically pure. Therefore reactions of racemic sulfoxides are for the most part excluded from this review. For more general discussions, the reader is referred to other chapters in this volume and to other reviews on the chemistry of sulfoxides. Especially useful are the reviews by Johnson and Sharp and by Mislow in the late 1960s and by Oae and by Nudelman as well as a book by Block . A review by Cinquini, Cozzi and Montanari" through mid-1983 summarizes the chemistry and stereochemistry of optically active sulfoxides. This chapter emphasizes results reported from 1984 through mid-1986. 

IV. ADDITION OF NUCLEOPHILES TO P-UNSATURATED SULFOXIDES A. /J-Keto sulfoxides... 

Prior literature indicated that olefins substituted with chiral sulfoxides could indeed be reduced by hydride or hydrogen with modest stereoselectivity, as summarized in Scheme 5.10. Ogura et al. reported that borane reduction of the unsaturated sulfoxide 42 gave product 43 in 87 13 diastereomer ratio and D20 quench of the borane reduction mixture gave the product 43 deuterated at the a-position to the sulfoxide, consistent with the hydroboration mechanism [10a]. In another paper, Price et al. reported diastereoselective hydrogenation of gem-disubstituted olefin rac-44 to 45 with excellent diastereoselectivity using a rhodium catalyst [10b],... 

A novel, unprecedented sulfoxide-directed borane reduction of the a,P-unsaturated sulfoxide to the saturated sulfide was discovered. 

The deuterium kinetic isotope effect between BH3-THF and BD3-THF was obtained by measuring the reaction rate constants of the two reactions with the unsaturated sulfoxide (Sj-40 independently via React-IR. The k(BH3)/k(BD3) is 1.4, consistent with hydrogen transfer not being the rate-limiting step [15, 16]. 

Sodium sulfide or hydrosulfide can be used in double Michael additions thus the bridged thiopyran (11) is formed from 2,7-cyclooctadienone (12),12 and dihydrodithiin oxides (13) and related compounds are similarly produced from unsaturated sulfoxides (14).13... 

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