Thiols addition reactions

C. Synthetic Utility of Asymmetrically Catalyzed Thiol Addition Reactions.105... 

Quinine and quinidine, as well as cinchonidine and cinchonine, are diastereo-meric pairs. However, at the critical sites—the P-hydroxyamine portions of the molecules—they are enantiomeric. Thus if quinine is used as the chiral catalyst in an asymmetric transformation (i.e., with one enantiomer being formed in excess), the other enantiomer is formed in excess when quinidine is used. Table 2 gives a representative example, the thiol addition reaction (19). 

B. Kinetic Resolution Using the Chiral-Amine-Catalyzed Thiol Addition Reaction (55)... 

The relatively high e.e. s obtained in most of the quinine-catalyzed thiol addition reactions, the wide range of enones and thiols potentially amenable to this reaction, and the versatility of the sulfur (and carbonyl) functionality combine to make this reaction useful in many ways. 

Recently Ikegami used the thiol addition reaction in the preparation of optically pure 4-phenylthioazetidin-2-one, the starting material for an elegant ( + )-thienamycin synthesis (58). When 4-phenylsulfonylazetidin-2-one was treated with cinchonidine and thiophenol, the intermediate azetinone underwent a thiol addition reaction and the 4-phenylthioazetidin-2-one was obtained in 54% optical and 96% chemical yield (eq. [13]). Recrystallization of the optically active aze-tidinone allows isolation of the pure enantiomer from the mother liquor. The phenylthio group is eliminated later in the synthesis of thienamycin. 

The thiol addition reaction discussed in the previous section does not lend itself readily to the preparation of (chiral) mercaptans. 

The example of the thiol addition reaction to a cyclohexadienone indicates that discrimination of this type can be carried out catalytically the proximity of the meso carbon to the reaction center increases the stereoselectivity substantially. 

The 1,4-thiol addition reaction lends itself well to a mechanistic study, for the following reasons ... 

The 1,4-addition of selenophenols to cycloalkenones proceeds smoothly under the same conditions used in the thiophenol addition (see Section V) (eq. [18]). Although the e.e. of the products is 40 to 65%, compared with the 60 to 80% achieved in the thiol addition reaction, the solid adducts are readily purified to enantiomeric purity by crystallization (63). 

Although the mechanism of this reaction has not been studied as thoroughly as that of the thiol addition reaction, there appears to be considerable similarity in the main features of the reaction. Thus, although the transition state may well differ in a number of details, the transition state shown earlier (Figure 10) appears to predict the correct configuration for the products of the selenophenol addition as well as of the thiophenol addition to cyclohexenones. 

Racemic thioglycerol (3-sulfanylpropane-l,2-diol) was used for the attachment of two lipid chains via ester bond formation with the hydroxy groups 82 while the free thiol group serves for selective cross-linking to other molecules via disulfide or sulfide bonds utilizing mild thiol-disulfide interchange or thiol addition reactions (Scheme 15).[163,164,167]... 

In this method, the cyclic peptide is generated through cysteine-perthioester cyclization to afford a Xaa-Cys bond whose thiol is then used for the second ligation step to the core through a thiol addition reaction (Scheme 25).[S71 For the perthioester cyclization, the linear precursor 91 consists of an activated N-terminal Cys(Npys) and a C-terminal thiocarboxylic acid which favors cyclization due to intramolecular mixed disulfide formation between them. 

In accordance with the above discussion, general base catalysis is not found in thiol addition reactions to aldehydes and ketones only specific base catalysis is prevalent (Lienhard and Jencks, 1966). This is in contrast to the general base-catalyzed hydration of ketones or aldehydes. The reactions of the carbonyl group at the carboxylic acid level of oxidation have much in common with the reactions of the carbonyl group at the aldehyde or ketone level of oxidation. In an excellent review on simple carbonyl addition reactions Jencks (1964) has discussed in detail the mechanisms of catalyzed additions to the carbonyl group of ketones and aldehydes. For general base-catalj ed additions the mechanism... 

CsF/A1203 was also used for deacylation reactions [48]. Among several inorganic supported CsF systems, Celite-supported CsF has been used for many reactions, such as N-alkylaliori, oxidation of thiols, addition reaction and Williamson synthesis [49-54]. 

Scheme 3. Synthesis of lipo-peptide derivatives via the rnaleimide thiol addition reaction.

Thiol-addition reactions and their applications in thiol recognition 13CSR6032. 

This method is potentially the most versatile, since it can be carried out in a variety of ways and adds relatively little to the cost of the final polymer. The nitroso-ene reaction in natural rubber already referred to is one example of such a modification. However, in order to avoid the necessity to gear the modification process to the vulcanisation reaction, we have concentrated in our own work on antioxidant adduct formation to the rubber double bonds either by vinyl grafting or by the Kharasch thiol addition reaction... 

The thermal reaction of 1,1-dimethoxyethylene with butyrolactones is reported to give substituted a-methylenebutyrolactones, e.g, (48), in good yield. The methylene group of a-methylenebutyrolactones can be protected by a reversible thiol addition reaction. ... 

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