S-nucleophiles

Sulfur is directly below oxygen on the periodic table (in Column 6A). Therefore, the chemistry of sulfur-containing compounds is very similar to the chemistry of oxygen-containing compounds. In the previous section, we saw a method for converting a ketone into an acetal  

In much the same way, a ketone can also be converted into a fAioacetal (thio means sulfur instead of oxygen)  

The main difference is that we use BF3 instead of H+ to make the earbonyl group more electrophilie  

Other than this small difference, making a thioacetal is very similar to making an acetal. After all, they are very similar in structure  

But thioacetals will undergo a transformation not observed for acetals. Specifically, thioacetals are reduced when treated with Raney nickel  

Also aromatic nitro compounds with the vacant ort/to-position relative to the nitro group can be regarded as a good structural basis for the synthesis of condensed nitrogen heterocycles through cyclizations with this nitro group or by means of intramolecular displacement of the latter (for numerous examples of these transformations, [214], authored by professors Svyatoslav Shevelev and Alexey Starosotnikov). 

7 Tandem Sn -Sn , Sn -Sn, and SN -Metal-Catalyzed Cross-Coupling Reactions 

The synthesis of fused derivatives by using the tandem An—An, An-Sn and Sn -Sn reactions proved to be a very constructive approach [11,114—116, 169-179]. A variety of 1,4-diazines condensed with five- and six-membered heterocycles have been obtained by reacting 1,4-diaziiuum (pyrazinium, quinoxalinium. 

A good example of the tandem oxidative reactions is cyclization of 

In summary, the examples given above show that metal-free Sn transformations are complementary to both classic substitutions and metal-catalyzed cross-coupling reactions, and their combinations can be exploited as a powerful synthetic tool to construct a variety of organic molecules. 

Data on reactions of sulfur nucleophiles with azoles are sparse. Oxazoles are transformed in low yield into the corresponding thiazoles over alumina with H2S at 350°C (74AHC(17)99). Sulfur nucleophiles such as SH or RS add to 1,3-dithiolylium salts at the 2-position (80AHC(27)l5i). 

There are a number of examples in which 1-alkoxybenzimidazoles, l-alkoxy-3-methylbenzimidazo-lium salts, and 1-alkylbenzimidazole 3-oxides react with anionic sulfur species to give 2-substitution with simultaneous deoxygenation (93CHE127). 

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Various S-nucleophiles are allylated. Allylic acetates or carbonates react with thiols or trimethylsilyl sulfide (353) to give the allylic sulfide 354[222], Allyl sulfides are prepared by Pd-catalyzed allylic rearrangement of the dithio-carbonate 355 with elimination of COS under mild conditions. The benzyl alkyl sulfide 357 can be prepared from the dithiocarbonate 356 at 65 C[223,224], The allyl aryl sufide 359 is prepared by the reaction of an allylic carbonate with the aromatic thiol 358 by use of dppb under neutral condi-tions[225]. The O-allyl phosphoro- or phosphonothionate 360 undergoes the thiono thiolo allylic rearrangement (from 0-allyl to S -allyl rearrangement) to afford 361 and 362 at 130 C[226],... 

The action of sulfur nucleophiles like sodium bisulfite and thiophenols causes even pteridines that are unreactive towards water or alcohols to undergo covalent addition reactions. Thus, pteridin-7-one smoothly adds the named S-nucleophiles in a 1 1 ratio to C-6 (65JCS6930). Similarly, pteridin-4-one (73) yields adducts (74) in a 2 1 ratio at C-6 and C-7 exclusively (equation 14), as do 4-aminopteridine and lumazine with sodium bisulfite. Xanthopterin forms a 7,8-adduct and 7,8-dihydropterin can easily be converted to sodium 5,6,7,8-tetrahydropterin-6-sulfonate (66JCS(C)285), which leads to pterin-6-sulfonic acid on oxidation (59HCA1854). 

The reaction of 1,2,4-triazine 4-oxides 55 with thiophenols proceeds in the same manner, resulting in the corresponding 5-arylmercapto-1,2,4-triazines 80 in high yields. Thiophenols in this case react as S-nucleophiles, in spite of the relative phenols—the C-nucleophiles (01RCB1068). 

Reaction of 2-chloromethyl-4//-pyrido[l,2-u]pyrimidine-4-one 162 with various nitronate anions (4 equiv) under phase-transfer conditions with BU4NOH in H2O and CH2CI2 under photo-stimulation gave 2-ethylenic derivatives 164 (01H(55)535). These alkenes 164 were formed by single electron transfer C-alkylation and base-promoted HNO2 elimination from 163. When the ethylenic derivative 164 (R = R ) was unsymmetrical, only the E isomer was isolated. Compound 162 was treated with S-nucleophiles (sodium salt of benzyl mercaptan and benzenesulfinic acid) and the lithium salt of 4-hydroxycoumarin to give compounds 165-167, respectively. 

No addition products with S-nucleophiles have yet been reported except for the reaction of 2-methylthio-4,6-diphenylthiopyrylium iodide with sodium thiophenolate involving a 2//-thiopyran intermediate (86S916). 

Nucleophilic displacement by amines and O and S nucleophiles. Subsequent access to inline, carbamate, sulfonamide functions... 

For substituted anilines (Thompson and Williams, 1977) and for 1-naphthylamine and a series of derivatives thereof (Castro et al., 1986a), k2 and the ratio Ar 2/Ar3 have been determined for nucleophilic catalysis with Cl-, Br-, SCN-, and SC(NH2)2. The values of k2 correspond fairly well to those found for the diazotization of aniline, but those of Ar 2/Ar3 increase markedly in the above sequence (Table 3-1). As k3 is expected to be independent of the presence of Cl- or Br- and to show little dependence on that of SCN- or thiourea, the increase in k 2/k3 for this series must be due mainly to 2. Indeed, the value of log(Ar 2/Ar3) shows a linear correlation with Pearson s nucleophilicity parameter n (Pearson et al., 1968). This parameter is based on nucleophilic substitution of iodine (as I-) in methyl iodide by various nucleophiles. The three investigations on nucleophilic catalysis of diazotization demonstrate that Pearson s criteria for bimolecular nucleophilic substitution at sp3 carbon atoms are also applicable to substitution at nitrogen atoms. 

Cir—R S Nucleophilic substitution, conjugate addition and epoxide ring-opening h... 

Lyashenko, Yu.E. and V.B. Sokolov. "Reactions of 0-(Alkylchloroformoimino)trichloromethylphos-phoranes With S-Nucleophiles." Phosphorus, Sulfur and Silicon and the Related Elements 69 (1992) 153-161. 

S-Nucleophiles are very reactive in 1,3-addition reactions with nitrile oxides. A series of a-glucosinolates 27 (R = CR1=NOH R1 =Ph, CH2PI1, CH2CH2PI1, ( )-CH=CHPh, 3-indolylmethyl) was prepared by addition reactions of thiol 27 (R = H) with nitrile oxides (123). The indolyl-substituted glucosinolate was then converted to a-glucobrassicin 28. 

C-nucleophile (X = active H-borate, boronate) N-nucleophile (amine, NaN3, tosyl amide, amide, lactam, imine, carbamate, urea) O-nucleophile (alcohol, acid, carbonate) S-nucleophile (PhS02Na)... 

But using Ingold s nucleophilic-electrophilic nomenclature, all "basic" reagents, organic or inorganic, are nucleophilic and "basicity" ("affinity" for... 

Photochemical addition of ammonia and primary amines to aryl olefins (equation 42) can be effected by irradiation in the presence of an electron acceptor such as dicyanoben-zene (DCNB)103-106. The proposed mechanism for the sensitised addition to the stilbene system is shown in Scheme 7. Electron transfer quenching of DCNB by t-S (or vice versa) yields the t-S cation radical (t-S)+ Nucleophilic addition of ammonia or the primary amine to (t-S)+ followed by proton and electron transfer steps yields the adduct and regenerates the electron transfer sensitizer. The reaction is a variation of the electron-transfer sensitized addition of nucleophiles to terminal arylolefins107,108. 

To compare the reactivities of various nucleophiles, the reactions of PECH with equimolar amounts of nucleophiles were carried out at 90°C for 16 h in DMF and the conversion was estimated by titration of chloride ion liberated. The results were summarized in Table 1. The reactivity of S-nucleophile is high as in general. The xanthate obtained was soluble in DMF, but insolubilized gradually on drying. Photosensitive PECH-N, is obtained in good yield notwithstanding the low solubility of sodium azide in DMF. 

Reaction of (24a) or (24b) with (16), (18) or (19) under the conditions of EGA catalysis leads selectively to substitution in the 2-position, Scheme 11, via the common cationic intermediate. Reaction with O- (or S-) nucleophiles such as MeOH, Scheme 11, exclusively gives substitution in the 4-position [35]. The difference in regioselectivity has been interpreted as 2-substitution arising from... 

Figure 1. Mechanism of a retaining / -glucosidase. OR = the aglycone Nu = the enzyme s nucleophile HA = the enzyme s acid catalyst.

Interaction 7a features net electron donation from the alkene n orbital (HOMO) to the vacant carbene p orbital (LUMO), and tracks the electrophilic character of the carbene. Interaction 7b represents electron donation from the filled carbene a orbital (HOMO) to the vacant alkene ti orbital (LUMO) and reflects the carbene s nucleophilic character. Both interactions operate simultaneously in the addition transition state, but which one is dominant ... 

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