Sulfonyl derivatives

The conversion of esters to hydrazides and of hydrazides to the sulfonyl derivatives occurs in good yield in the McFadyen-Stevens synthesis, but the decomposition of sulfonyl derivatives gives low yields of the desired products, for example, thiazole hydrazide (28) with 10% excess of PhSOjCl in pyridine gave a 75% yield of l-phenylsulfonyl-2-(4-methyl-5-thiazo ecarbonyl)hydrazine (29) (66). The Newman-Caflish modification of the McFadyen-Stevens synthesis gave 37% 4-methyl-5-thiazole-carboxaldehyde (30) (Scheme 27). 

The isocyanide dichlorides are particularly attractive 1,1-bielectrophiles, and the N-sulfonyl derivative (138) underwent reaction with the iV-hydroxythioamide (137) to give the 1,3,5-oxathiazole derivative (139) (71AP763). Yields varied from 62% for R = Me and were slightly less for R = Ph (57%) and R = p-MeOC6H4 (50%). 

PROTECTION FOR IMIDAZOLES, PYRROLES, AND INDOLES A -Sulfonyl Derivatives... 

Benz[/]isoindole (125), recently prepared from the p-toluene-sulfonyl derivative (124), proved to be too unstable for isolation, but eould be trapped in solution as the Diels-Alder adduct (127). The corresponding 1-phenyl derivative (126) was also prepared and, aecording to spectral measurements, reacts with maleic anhydride to give the product (128) derived by additive substitution. This subsequently rearranged to the adduct (129). The same behavior is observed in the reaction of (126) with V-phenylmaleimide. This provides the first clear indication that substitution products from isoindole derivatives and dienophiles can be converted into the normal addition products. 

In contras t with dially lamines and their sulfonyl derivatives, IV-acy Idially lamines react with tellurium tetrahalides to give zwitterionic oxazolines 29 containing five-coordinated tellurium (85T1607). Molecular and crystal structures of one of this type of compound (29, R = Me, X = Cl) were studied by X-rays (85T1607). 

The 3-nitroindoles show interesting reactivity toward the anion of ethyl isocyanoacetate iV-sulfonyl derivatives give the pyrrolo[3,3-b indole ring system lEq. 10.38. " On the other hand, iV-alkoxycarbonyl derivatives give the normal product, the pyrrolo[3,4-li indole ring system fEq, 10,39, ... 

In contrast to the A-sulfonyl derivatives, Ar-acylcyclohexadienamines 5, on treatment with p-toluenesulfonic acid in toluene at 20 C, yield 3 a,7a-dihydrobenzoxazoles 6 rather than 1-substituted 1//-azepines.21 However, the dihydrobenzoxazoles 6 are thermally unstable and on heating at 180X rearrange smoothly to the 1-acyl-l//-azepines 7 in high yields. 

FIGURE 19. Molecular configuration of XSOzY sulfonyl derivatives and the r sin a versus r cos a plot characterizing the variations of O O nonbonded distances with changing S=0 length (r) and 0=S=0 angle (2a). 

Trialkylboranes react rapidly and in high yields with a-halo ketones,a-halo esters, a-halo nitriles, and a-halo sulfonyl derivatives (sulfones, sulfonic esters, sulfonamides) in the presence of a base to give, respectively, alkylated ketones, esters, nitriles, and sulfonyl derivatives. Potassium tert-butoxide is often a suitable base, but potassium 2,6-di-tert-butylphenoxide at 0°C in THF gives better results in most cases, possibly because the large bulk of the two tert-buXy groups prevents the base from coordinating with the R3B. The trialkylboranes are prepared by treatment of 3 mol of an alkene with 1 mol of BH3 (15-16). With appropriate boranes, the R group transferred to a-halo ketones, nitriles, and esters can be vinylic, or (for a-halo ketones and esters) aryl. " °... 

The alkylation of activated halogen compounds is one of several reactions of trialkylboranes developed by Brown (see also 15-16,15-25,18-31-18-40, etc.). These compounds are extremely versatile and can be used for the preparation of many types of compounds. In this reaction, for example, an alkene (through the BR3 prepared from it) can be coupled to a ketone, a nitrile, a carboxylic ester, or a sulfonyl derivative. Note that this is still another indirect way to alkylate a ketone (see 10-105) or a carboxylic acid (see 10-106), and provides an additional alternative to the malonic ester and acetoacetic ester syntheses (10-104). 

FIGURE 22. Partial CS(d) Wiberg indexes characterizing d-orbital participation plotted against the experimentally determined S—C bond lengths in some sulfonyl derivatives . 

Proteases are enzymes that break peptide bonds in proteins. As such they lend themselves to a variety of homogeneous assay techniques. Most employ labeling both ends of the substrate with a different tag, and looking for the appearance (disappearance) of the signal generated in the intact substrate (product). As an example, for a fluorescence quench assay, the N-terminal of a peptide is labeled with DNP and the C-terminal with MCA. As such, the peptide is fluorescently silent since the fluorescence from DNP is quenched by absorption by the MCA. Another very popular donor/acceptor pair is EDANS 5-[(2-aminoethyl)amino] naphthalene-1-sulfonic acid and DABCYL 4-(4-dimethylaminophenylazo)benzoic acid) (a sulfonyl derivative (DABSYL) [27], Upon peptide cleavage, the two products diffuse, and due to a lack of proximity, the fluorescence increases. 

The readily available enantiopure acyclic hydroxy 2-sulfinyl butadiene 585 undergoes a highly face-selective Diels-Alder cycloaddition with PTAD to generate the densely functionalized cycloadduct 586 (Equation 84). The complete reversal of facial selectivity is observed when sulfonyl derivative 587 is treated with PTAD under identical conditions (Equation 85). These results demonstrate that the sulfinyl functionality is not just synthetically useful but also an extremely powerful element of stereocontrol for intermolecular Diels-Alder cycloadditions. On the other hand, the corresponding ( , )-hydroxy-2-sulfinyldienes treated with PTAD affords the cycloadducts in high yield but with moderate 7i-facial selectivity <1998CC409, 2005CEJ5136>. 

The furoxans with functionally substituted alkyl groups in the 3,4-position have proved to be useful for the synthesis of thiosubstituted furoxanes (Schemes 26 and 27), which can be oxidized to sulfonyl derivatives (Scheme 26) <2001EJM771>. 

The simplified preparations128 of 5-O-sulfonylated derivatives of 1,2-O-isopropylidene-a-D-gIucofuranose (77 and 78) (see Section VI,4) was the key to substantial improvements in the synthesis of L-idose. 

A number ofwater soluble sulfonyl derivatives (44, X=S02, n=2,3) and some related compounds (44, X=Q,S, n=2,3) bearing a chain with a basic function at the ring, have... 

Similarly to the sydnonimines, unsubstituted oxatriazolium-5-amenates have been acylated with various acylating systems to N-acyl-, N-carbamoyl-, N-alkoxycarbonyl-and N-sulfonyl-derivatives [148] that represent chemically stable compounds (Scheme... 

Reactivity toward nucleophiles and comparison with other electrophilic centers 152 Paths for nucleophilic substitution of sulfonyl derivatives 156 Direct substitution at sulfonyl sulfur stereochemistry 157 Direct substitution at sulfonyl sulfur stepwise or concerted 158 The elimination-addition path for substitution of alkanesulfonyl derivatives 166 Homolytic decomposition of a-disulfones 172 10 Concluding remarks 173 Acknowledgement 174 References 174... 

The reactions represented by (191) are all nucleophilic substitutions occurring at a sulfonyl sulfur. Besides cpdisulfones substitutions of this kind are also of frequent occurrence in the chemistry of many other types of sulfonyl derivatives such as sulfonyl halides, aryl esters of sulfonic acids, etc., and many of the general aspects of their behaviour and mechanism have been examined in considerable detail. Most of the remainder of this section will be devoted to consideration of the results of such studies. 

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