Sulfoxides nitrile synthesis

This procedure, which involves the addition of an anion derived from a nitrile to an unactivated acetylenic bond under rather mild conditions, is a convenient general method for the synthesis of a-vinyl-nitriles (see Table I). The reaction proceeds smoothly in either dimethyl sulfoxide or hexamethylphosphoric triamide (see p. 103 for warning) as solvent with a tetraalkylam monium salt as catalyst. The products thus prepared are obtained in yields higher2 than those obtained under conventional conditions, which generally require higher temperatures and elevated pressures.3-4... 

The oxidation of thioamides 63 with a wide variety of oxidizing agents is a well-employed method for the synthesis of 3,5-disubstituted-l,2,4-thiadiazoles 64 <1982AHC285>. However, this method is limited mainly to arylthioamides. The most common oxidizing agents tend to be halogens, hydrogen peroxide, dimethyl sulfoxide (DMSO), and nitrous acid. Yields from these reactions are variable and depend on the thioamide, oxidant, and conditions used (Equation 19). By-products such as nitriles and isothiocyanates are usually formed. 

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]. 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

The conjugate addition of heteronucleophiles to activated alkenes has been used very often in organic synthesis to prepare compounds with heteroatoms [3 to various activating functional groups, e.g. ketones, esters, nitriles, sulfones, sulfoxides and nitro groups. As in the Michael reaction, a catalytic amount of a weak base is usually used in these reactions (with amines as nucleophiles, no additional base is added). 

The preparation of a-selenoketones, esters, nitriles and related compounds can easily be performed via alkylation of the corresponding enolates or stabilized carbanions [21]. These compounds have found many synthetic applications in radical chemistry. In Eq. (9), a typical example involving a ketone is depicted [22]. The stability of a-selenoketones such as 41 is remarkable. Similar reactions with lactones have been performed. For instance, this approach has been applied to the stereoselective synthesis of oxygen-containing rings to either faces of a bicyclic structure [23]. The approach based on a-selenenylation/radical allyla-tion compares favorably with classical enolate allylation procedures, which usually leads to mixture of mono- and diallylated compounds. Furthermore, this strategy is excellent for the preparation of quaternary carbon centers [24] as shown by the conversion of 43 to 45, a key intermediate for the synthesis of fredericamycin A, [Eq. (10)] [25]. Similar reactions with sulfoxides [26] and phosphonates [27] have also been reported. 

Where solubility alone is the issue, simply changing solvent to permit all species to be dissolved allows the chemistry to proceed essentially as it would in aqueous solution were species soluble. Typical molecular organic solvents used in place of water include other protic solvents such as alcohols (e.g. ethanol), and aprotic solvents such as ketones (e.g. acetone), amides (e.g. dimethylformamide), nitriles (e.g. acetonitrile) and sulfoxides (e.g. dimethylsulfoxide). Recently, solvents termed ionic liquids, which are purely ionic material that are liquid at or near room temperature, have been employed for synthesis typically, they consist of a large organic cation and an inorganic anion (e.g. lV, lV,-butyl(methyl)-imidazolium nitrate) and their ionic nature supports dissolution of, particularly, ionic complexes. 

Enzymatic desymmetrization of substituted 1,3-propanediols has been used as key step in the synthesis of y-butyrolactones by Itoh and coworkers, Scheme (8) [54],The diols 43 were treated with lipase PS (Pseudomenas sp.) in the presence of vinyl acetate as acyl donor to afford acetates 44 in excellent chemical yields and very high enantiomeric excesses (90-98%). These monoacetates were then converted into hydroxy nitriles 46 using a three step procedure. Tosylation of the hydroxyl group of 44, followed by treatment with potassium cyanide in dimethyl sulfoxide at 80°C gave the corresponding acetates 45. The acetoxy groups of 45 were finally hydrolysed with lithium hydroxide in a... 

Other activated sulfoxides. This alkylative elimination reaction has been extended by Trost and Bridges to a one-pot synthesis of alkenes, vinyl sulfides, a, l-unsaturated sulfoxides, and a,j3-unsaturated nitriles. The sulfoxides (1-4) are converted into the anions by lithium N-isopropylcyclohexylamide or sodium hydride and are then alkylated at 20° in THE or DME elimination is then effected by raising the temperature to reflux. In some cases trimethyl phosphite is added as a scavenger for phenylsulfenic acid. Typical results are formulated in the equations. The elimination reaction is facilitated by an aryl, thioaryl, or... 

Lithiated a-amino nitriles derived from an enantiomerically pure secondary amine have been used to achieve the asymmetric synthesis of trfl 5-dibenzylbutyrolactones (scheme 10) [58]. Enantiomeric excesses of greater than 96% were obtained after removing the chiral auxiliary. When aromatic aldehydes were used as electrophiles the benzylic alcohols were obtained as a mixture of the two epimers with a diastereomeric excess of 60-75%. Addition of a chiral sulfoxide, prepared using a modified Sharpless oxidation, to butenolide has also been utilised as part of an expeditious synthesis of podophyllotoxin (scheme 11) [59]. 

Dihalocarbenes produced under PTC conditions have been advantageously used in the classical isonitrile synthesis from primary amines, again giving higher yields than the classical procedure. Hydrazine affords diazomethane, amides are dehydrated to nitriles and sulfoxides are reduced to sulfides in high yields. Finally, alcohols are converted into halides (Table 17)... 

Dilithium tetrachlorocuprate is recommended as an additive for cross coupling of Grignard compounds with tosylates even allylic and benzylic acetates give good yields . a-Methylene-ketones, -carboxylic acids and -lactones have been prepared via sulfides and sulfoxides. A convenient and general synthesis of acetylene derivatives from boranes via the reaction of iodine with lithium 1-alkynyltriorganoborates has been published ar-Nitrostyrenes can be easily obtained by a Wittig synthesis with formaldehyde in an aqueous medium . A new synthesis of unsym. ketones by reaction of dialkyldiloroboranes with lithium aldimines has recently been published . Metallo aldimines have also served for the synthesis of a variety of other compound classes such as a-hydroxyketones, a-keto acids, nitriles, and for the asym. synthesis of a-amino acids . Polycondensations of malononitriles with benzylic chlorides have been carried out quantitatively under mild conditions in dimethyl sulfoxide with triethylamine as acid acceptor . Carbonyl compounds can react with dibromoacetonitrile to yield a-bromo esters with additional carbon atom . ... 

Dry methyl methylthiomethyl sulfoxide allowed to react at room temp, with NaH in tetrahydrofuran, benzonitrile added, and stirred 16 hrs. at 50 l-methylsulfinyl-l-methylthio-2-amino-2-phenylethylene. Y 75%. - This is the first step of a method for the synthesis of a-aminocarboxylic acid derivs. from nitriles with addition of 1 C-atom. F. e. s. K. Ogura and G. Tsudiihashi, Am. Soc. 96,1960 (1974). 

For a recent synthesis of a-oxoacid amides from nitriles using methyl methylthiomethyl sulfoxide see ref. (478). Further interconversions between a-acylamino-a-hydroxy acid derivatives and the corresponding a-acylamino-a-aryl(alkyl)thio-, a-arylamino- and a-alkoxy compounds were reported (479, 480, 511). 

Ogura, K., N. Katoh, I. Yoshimura, and G. Tsuchihashi New Synthesis of a-Keto Acid Derivatives From Nitriles Using Methyl Methylthiomethyl Sulfoxide. Tetrahedron Letters 1978, 375. 

There are many examples of the synthesis of homoleptic solvento-complexes by halide abstraction from compounds containing both coordinated halides and solvento-ligands. Palladium chloride is known to dissolve in nitriles, dimethylformamide, and dimethyl sulfoxide with the formation of complexes of the type [PdCl2(solv)2] which can be isolated as solids.3 The reaction of [PdCl2(RCN)2] with an excess of silver ions s is a convenient method for the synthesis of [Pd(RCN)4]2+. The tetra(acetonitrile)-platinum(II) and tetra(propionitrile)platinum(II) salts have been prepared in this way (Scheme 4.6). Wayland and Schramm have synthesized homoleptic palladium(II) complexes with DMSO, DMF, and DMAA in a similar manner. 

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