Sulfoxides additions

Introduction of a sulfur atom into saturated hydrocarbons leads to a considerable decrease, by an order of magnitude, in the yield of radicals [G(radicals) for hydrocarbons 420]. This was explained as due to the existence of low-lying d-orbitals at the sulfur atom. This explanation agrees with the observation that this decrease is smaller in the case of insertion of a SO group, as there are four p electrons of the S atoms which may be excited at the d-orbital for sulfide and only two p electrons in the case of sulfoxides. Additional proof is that for sulfones, where there is no available p electron, the yield of the radicals [G(radicals) = 3.7 for tetramethylene sulfone] is about the same as for hydrocarbons. 

While cuprate addition to chiral 2-acetoxy-3-butenyl aryl sulfoxides gave exclusively the (-E)-allylic sulfoxides, addition to chiral butadienyl sulfoxide provided a mixture of E- and Z-isomers with a preference for the Z-isomer68. 

In a more detailed investigation, it was found that the metallacyclobutane intermediate 4, on treatment with dimethyl sulfoxide, additionally regenerated the tetracyclic starting material in small amounts. When heating the primary complex in chloroform, 2-methylene-4-vinyl-bicyclo[3.1.0]hexane was the major decomplexation product. Reaction of the platinacyclo-butane 4 with diazomethane gave 2,4-divinylbicyclo[3.1.0]hexane and the tetracyclic starting material. ... 

Scheme 5.39. Allyl sulfoxide additions , fa 1,4-mechanism [198]. (b) Tandem 1,2-addition / 3,3-rearrangement mechanism [148] (see also ref. [199]). (c,d) Transition structures for allyl phosphine oxides [196,197]. Inset Gauche pentane interaction between lithium and the N/je methyl.

Photolysis of methyl styryl sulfoxide in alcohols provides three types of products, based on two types of chemistry [110]. One process is deoxygenation to provide 220. Both it and the starting material are subject to the addition of alcohols across the olefin. (It is worthwhile to note that conjugation to the low energy chromophore was necessary for deoxygenation.) In methanol, the two diastereomers of the alcohol/sulfoxide addition product are formed in 1 1 ratio with a total yield of 65% at complete conversion. 

Heterogeneous catalytic oxidation of sulfides in ionic liquids by anhydrous H2O2 or urea hydroperoxide with MCM-41 and related mesoporous catalysts containing Ti or Ti and Ge was studied by Hardacre and coworkers [51]. The Ti-based catalyst gave a quite selective sulfoxidation. Addition of Ge to Ti increased the rate of the oxidation but reduced the selectivity toward sulfoxide [51a]. 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Trifluoromethanesulfonic acid is miscible in all proportions with water and is soluble in many polar organic solvents such as dimethylformamide, dimethyl sulfoxide, and acetonitrile. In addition, it is soluble in alcohols, ketones, ethers, and esters, but these generally are not suitably inert solvents. The acid reacts with ethyl ether to give a colorless, Hquid oxonium complex, which on further heating gives the ethyl ester and ethylene. Reaction with ethanol gives the ester, but in addition dehydration and ether formation occurs. 

I itro-DisplacementPolymerization. The facile nucleophilic displacement of a nitro group on a phthalimide by an oxyanion has been used to prepare polyetherimides by heating bisphenoxides with bisnitrophthalimides (91). For example with 4,4 -dinitro monomers, a polymer with the Ultem backbone is prepared as follows (92). Because of the high reactivity of the nitro phthalimides, the polymerkation can be carried out at temperatures below 75°C. Relative reactivities are nitro compounds over halogens, Ai-aryl imides over A/-alkyl imides, and 3-substituents over 4-substituents. Solvents are usually dipolar aprotic Hquids such as dimethyl sulfoxide, and sometimes an aromatic Hquid is used, in addition. 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

The initiating step in these reactions is the attachment of a group to the sulfoxide oxygen to produce an activated intermediate (5). Suitable groups are proton, acyl, alkyl, or almost any of the groups that also initiate the oxidations of alcohols with DMSO (40,48). In a reaction, eg, the one between DMSO and acetic anhydride, the second step is removal of a proton from an a-carbon to give an yUde (6). Release of an acetate ion generates the sulfur-stabilized carbonium ion (7), and the addition of acetate ion to the carbonium ion (7) results in the product (eq. 15) ... 

Extraction Solvent. Dimethyl sulfoxide is immiscible with alkanes but is a good solvent for most unsaturated and polar compounds. Thus, it can be used to separate olefins from paraffins (93). It is used in the Institute Fransais du Pntrole (IFF) process for extracting aromatic hydrocarbons from refinery streams (94). It is also used in the analytical procedure for determining polynuclear hydrocarbons in food additives (qv) of petroleum origin (95). 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Isomerization of 3-cephems (27) to 2-cephems (28) takes place in the presence of organic bases (e.g. pyridine) and is most facile when the carboxyl is esterified. Normally an equilibrium mixture of 3 7 (3-cephem/2-cephem) is reached. Since the 2-cephem isomers are not active as antibacterial agents, the rearrangement proved to be an undesirable side reaction that complicated acylation of the C-7 amine under certain conditions. A method for converting such mixtures to the desired 3-cephem isomer involves oxidation with concomitant rearrangement to the 3-cephem sulfoxide followed by reduction. Additions... 

The intermediate sulfenic acid derived from a penicillin sulfoxide has been trapped by a large assortment of reagents and, in one case, the sulfenic acid itself has been isolated (74JA1609). Only some of these products will be discussed here, and the reader is referred to the cited reviews (especially B-80MI51102) for additional examples. 

Dried with Linde type 5A molecular sieves or Na2S04 and fractionally distd at reduced pressure. Alternatively, it was refluxed with, and distd from, BaO. Also purified by fractional crystn from the melt and distd from zinc dust. Converted to its phosphate (m 135°) or picrate (m 223°), which were purified by crystn and the free base recovered and distd. [Packer, Vaughn and Wong J Am Chem Soc 80 905 1958.] The procedure for purifying via the picrate comprises the addition of quinoline to picric acid dissolved in the minimum volume of 95% EtOH to yield yellow crystals which are washed with EtOH and air dried before recrystn from acetonitrile. The crystals are dissolved in dimethyl sulfoxide (previously dried over 4A molecular sieves) and passed through a basic alumina column, on which picric acid is adsorbed. The free base in the effluent is extracted with n-pentane and distd under vacuum. Traces of solvent are removed by vapour phase chromatography. [Mooman and Anton J Phys Chem 80 2243 1976.]... 

---