Sulfoxides nucleophilic additions

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. 

Nucleophilic addition to acetylenic sulfoxides provides a,/ -ethylenic sulfoxides. Treatment of 181 with monoalkyl-copper afforded nearly quantitatively /J-alkylated a, / -ethylenic sulfoxides 182 through cis-addition to the triple bond. The reaction with lithium dimethylcuprate also afforded a similar adduct however, the reaction with lithium di-n-butylcuprate was found to give a small amount of ethyl n-butyl sulfoxide 183 besides the... 

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). 

Nucleophilic addition of a-lithiated sulfoxides to a-PBN, followed by oxidation, gives (S-sulfinyl nitroxyl radicals (383) (Scheme 2.166) (621). 

Addition of Lithiated Sulfoxides and Sulfones Nucleophilic addition of lithiated methylaryl sulfoxides (384) to nitrones of various structures proceeds easily and in good yields (622). The reactions are applied to the synthesis of optically active a-substituted and a,a-disubstituted hydroxylamines, to secondary amines (623), and to enantioselective syntheses of alkaloids (624). The preferred approach to (+ )-euphococcinine is based on the use of homochiral 3-sullinyl nitrones (385) (Scheme 2.167). 

Several trivial but highly useful reactions are known to convert one acceptor-substituted allene into another. For example, the transformation of allenic carboxylic acids is possible both via the corresponding 2,3-allenoyl chlorides or directly to 2,3-allen-amides [182,185], Allenylimines were prepared by condensation of allenyl aldehydes with primary amines [199]. However, the analogous reaction of allenyl ketones fails because in this case the nucleophilic addition to the central carbon atom of the allenic unit predominates (cf. Section 7.3.1). Allenyl sulfoxides can be oxidized by m-CPBA to give nearly quantitatively the corresponding allenyl sulfones [200]. The reaction of the ketone 144 with bromine yields first a 2 1 mixture of the addition product 145 and the allene 146, respectively (Scheme 7.24). By use of triethylamine, the unitary product 146 is obtained [59]. The allenylphosphane oxides and allene-... 

Diethylamine can readily undergo nucleophilic addition with 1,2-allenyl sulfoxides to afford 2-diethylamino-2-enyl sulfoxides 181, which can be easily converted to a-hydroxy ketones 182 or /3-keto sulfoxides 183 [94]. 

The benzo[fc]thiophene sulfoxides, such as (142), generated from the parent benzo-thiophene on the H202-TFA-mediated oxidation, undergoes Michael-type nucleophilic addition of oxygen and sulfur nucleophiles in acidic media to produce 3-substituted benzo[fc]thiophenes (143). This method provides an easy two-step functionalization of 2-acylbenzo[fc]thiophene derivatives. ... 

Coordinated a-amino amides can be formed by the nucleophilic addition of amines to coordinated a-amino esters (see Chapter 7.4). This reaction forms the basis of attempts to use suitable metal coordination to promote peptide synthesis. Again, studies have been carried out using coordination of several metals and an interesting early example is amide formation on an amino acid imine complex of magnesium (equation 75).355 However, cobalt(III) complexes, because of their high kinetic stability, have received most serious investigation. These studies have been closely associated with those previously described for the hydrolysis of esters, amides and peptides. Whereas hydrolysis is observed when reactions are carried out in water, reactions in dimethyl-formamide or dimethyl sulfoxide result in peptide bond formation. These comparative results are illustrated in Scheme 91.356-358 The key intermediate (126) has also been reacted with dipeptide... 

Undoubtedly, the most widely used method for the synthesis of o.p. sulfoxides is the nucleophilic addition of metal organic reagent to an electrophilic sulfur with preestablished chirality, and the subsequent displacement of the sulfoxide. The reason is that either a good kinetic resolution of the sulfinyl chloride, generated first, or high separation factor of the intermediate diastereoisomers formed, permits the sulfinylating agent to be obtained in 100% de. 

Intramolecular nucleophilic addition of alkoxides to vinyl sulfoxides (90) provided a route to (3-alkoxysuIfoxides (91) (Scheme 24). The cij-product was formed with up to 18 1 selectivity.58 Alkoxide nucleophiles undergo an addition/elimi-nation protocol with P-iodo vinyl sulfoxides to yield tetrahydrofurans and tetrahy-dropyrans, which contain either an endo- or an exo-cyclic double bond.59,60... 

Silver salts are also utilized to perform nucleophilic additions to disulfide bonds to yield sulfenamides (146). If alkyl halides are treated with stoichiometric AgBF4 in dimethyl sulfoxide solvent (DMSO, solvent), the corresponding aldehydes/ ketones will form in good yields. This reaction is an alternative to the well-known Swern oxidation (147). In addition, silver can drive the formation of dialkylper-oxonium ions from alkyl halides, which then oxidizes sulfoxides or sulfides (148,149). In the presence of AgN03, sulfides can be oxidized into a-chloro sulfoxides by SO2CI2 (Fig. 36) (150). 

The sulfinyl group is a useful temporary chiral auxiliary for the activation of a carbon carbon double bond towards nucleophilic addition as both enantiomers of a,//-unsaturated vinyl sulfoxides are available in enantiomerically pure form91. Both intermolecular and intramolecular conjugate additions of V-nucleophiles have been investigated. 

Intramolecular addition of an a-sulfinyl carbanion to an isolated double bond occurs on treatment of medium-ring -homoallylic sulfoxides (58), (59), (60) and (61) with butyllithium (0.5 equiv. equations 16-19) < Kinetic data suggest that this process is a nucleophilic addition of a carbaruon (an a-lithiated sulfoxide) to a nonactivated double bond and takes place reattily, provided a suitable proton source is available. Normally the free sulfoxide is the proton donor species. ... 

The nucleophilic character ofdialkyl sulfides is illustrated by their nucleophilic addition reaction with alkyl halides to form the corresponding sulfonium salts (35) (Scheme 13). Asymmetric sulfonium salts (36) have a tetrahedral configuration therefore, like the analogous chiral saturated carbon compounds, they can be resolved into optical enantiomers (see Chapter 6, p. 81). They are, however, generally less optically stable than sulfoxides, but in sulfonium salts the unshared electron pair can hold its configuration at ordinary temperatures, unlike nitrogen in quaternary ammonium salts, enabling their resolution to be achieved. 

In a long series of papers, Oae and his group have studied the formation of biaryl compounds by ligand coupling occurring on a a-sulfurane, formed by nucleophilic addition of an organometallic species on the sulfur atom of the sulfoxide substrate E)epending on the nature of the two substituents... 

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