Sultams with nucleophiles

The Gabriel-Cromwell aziridine synthesis involves nucleophilic addition of a formal nitrene equivalent to a 2-haloacrylate or similar reagent [29]. Thus, there is an initial Michael addition, followed by protonation and 3-exo-tet ring-closure. Asymmetric variants of the reaction have been reported. N-(2-Bromo)acryloyl camphor-sultam, for example, reacts with a range of amines to give N-substituted (azir-idinyl)acylsultams (Scheme 4.23) [30]. 

The 3 + 2-cycloaddition of commercially available Me3SiCHN2 with camphor sultam-derived dipolarophiles produces 3-trimethylsilyl-substitutcd-A1 -pyrazolincs which on acid treatment convert into optically active A2-pyrazolines.60 The nucleophilic addition of ethyl diazoacetate with /V-cthoxycarbonyl-/V-(2,2,2-trichlorocthylidcne)a-mine produces a new diazo intermediate (35), which by 1,3-dipolar cycloaddition followed by a sigmatropic rearrangement of the cycloadduct (36) furnishes a substituted pyrazole (37) (Scheme 13).61. 

Intramolecular aziridinations of the olefinic sulfonamides 297, by means of the iminoiodane derivatives 298, have recently been demonstrated (Scheme 85) (OOOL2327). Ring-opening reactions of the bi- and tricyclic sultams 299, thus obtained, with selected nucleophiles were explored and provide access to functionalized cyclic sulfonamides. 

Camphor-10-sulfonic acid (1) is available in large quantities in both enantiomeric forms. In only 3 steps the cyclic sulfonamide 2 (sultam) can be synthesized, which can be acylated with acid chlorides after deprotonation with sodium hydride (Scheme 1) [1, 2]. The resulting amides 3 are considerable more reactive towards nucleophiles than the corresponding carboxylic esters and the a,/ -unsaturated derivatives undergo, with excellent selectivities, Diels-Alder reactions or Michael additions under mild conditions. Al-... 

Sultams, e.g. (187)-(189), suffer hydrolysis by treatment with acid or alkali. The reaction opens the sultam ring (Scheme 78). With acids, the hydrolysis involves initial protonation of the nitrogen atom followed by nucleophilic attack by X". In alkaline hydrolysis, the reaction involves nucleophilic attack by OH and subsequent cleavage of the nitrogen-sulfur bond (Scheme 78). The order of reactivity of sultams towards hydrolysis is p>y>8. This is to be expected since it parallels the relative instability of the ring systems, where the four-membered ring is more reactive than the five and six-membered rings. 

W-(p-toluenesulfinyl)bomane-10,2-sultam in the (/Jj-form delivers the sulfinyl group to various nucleophiles. Thus, chiral vinyl sulfoxide and p-toluenesulfinimines are readily prepared. Enantiopure ketones can be obtained from l,2-bis(benzenesulfonyl)alkenes via acetal formation with chiral diols such as (+)-l,2-diphenylethane-l,2-diol. ... 

The sultone cycloadducts could be further manipulated by ring-opening with various nucleophiles, such as alcohols and amines, at the y-position [41]. When optically active (S)-(-)-a-methylbenzylamine reacted with the racemic sultone cycloadduct 76 in ethanol at room temperature, one of the diastereomeric ammonium sulfonates precipitated from the reaction mixture (Scheme 17). Although the absolute stereochemistry of 77 had not been determined, cyclization of optically pure 77 with phosphorus oxychloride gave an optically pure sultam 78. Formic acid debenzylation followed by base hydrolysis of the N-formyl group afforded the optically pure sultam 80 in good yield [40]. 

Several reports of the reactions of /Fsultams with amines have been recorded. The sultams 122 and 123 are converted by the action of benzylamine to the corresponding sulphonamides (equation 215)242,269-27. Functionalized /Fsultams often undergo C—N bond fission under nucleophilic/basic conditions as shown in equation 216258. Whilst both 1,8-naphthosultam and its N-methyl derivative are essentially stable towards... 

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