Sultam

Sultones and Sultams. Compounds containing the group —SOj—O— as part of the ring are called -sultone. The —SOj— group has priority over the —O— group for lowest-numbered locant. 

Similarly, the —SOj—N= group as part of a ring is named by adding -sultam to the name of the hydrocarbon with the same number of carbon atoms. The —SOj— has priority over —N= for lowest-numbered locant. 

Fig. 6. Preparation of Oppol2er s chiral sultam auxiliary (85) and use of this chiral auxiUary for the preparation of t-phenylalanine.

Sulfonamides. A/-Halo-A/-alkylsulfonamides, RS02NR X, are relatively stable distillable Hquids. Under the influence of uvlight they form 1 1 adducts with olefins (67,100). Ai-/-Butyl derivatives rearrange forming precursors to cyclopropanes and sultams. A/-Halo-A/-sodioalk5lsulfonamidates, RS02NClNa, have been less extensively studied than their aromatic counterparts (70). The stabiHty of these compounds approaches that of the aromatic sulfonamides (80). The dodecyl compound exhibits properties of both a disinfectant and a surfactant. 

The possible structures for isothiazoles are discussed in Section 4.01.1, and attention in this chapter will be directed mainly towards the aromatic systems, as defined in Section 4.01.1. The saturated isothiazole 1,1-dioxides (5) are known as sultams, and bicyclic compounds of structure (6) are called isopenems. Isothiazoles readily coordinate to metals (76MI41703, 78MI41701, 79MI41700, 80MI41701). Coordination usually takes place through the nitrogen atom, but sulfur coordination can occur with soft metals such as cadmium or mercury. Some specific coordination complexes are discussed in later sections. 

Alternative ( soft ) ionization techniques are not usually required for aromatic isothiazoles because of the stability of the molecular ions under electron impact. This is not the case for the fully saturated ring systems, which fragment readily. The sultam (25) has no significant molecular ion under electron impact conditions, but using field desorption techniques the M + lY ion. is the base peak (73X3861) and enables the molecular weight to be confirmed. 

A few isothiazoles, 2,1-benzisothiazoles and monocyclic sultams have been prepared by methods involving formation of the 4,5-bond. Thus, condensation of a-cyanooximes (179) with ethyl mercaptoacetate or related compounds gives a compound (180) which cyclizes... 

From the Oppolzer sultam by exchange AllylOH, Ti(OR)4, 67-95% yield. 

Cava and Schlessinger have reported the synthesis of 1,2,3-triphenyl-isoindole (65) in 78% yield from 1,3-diphenylisobenzofuran (68) hy reaction with thionylaniline (69) and boron trifluoride. The mechanism proposed for this remarkable transformation involves reaiTangement of the adduct (70) derived from thionylaniline and the isobenzofuran, to the tricyclic intermediate (71). This presumably collapses to the S-sultam (72), which yields the isoindole (65) upon extrusion of sulfur dioxide. Loss of sulfur dioxide, both from S-sultones and unsaturated S-sultams, is well documented. ... 

Napht-sultam, n. naphthosultam, naphsultam. -sulton, n. naphthosultone, naphsultone. 

An alternative approach is to have the chiral auxiliary on the enolate. Sweeney has reported the addition of bromoacyl sultam 102 to phosphonyl imines 103, which afforded the cis- or trans-aziridines with high levels of diastereoselectivity depending on the imine substituent (Scheme 1.30) [55]. 

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 classical aza-Darzens reaction (between bromoenolates and imines) has been investigated by several groups in recent years, especially with respect to the design and execution of asymmetric variants. Both stoichiometric and catalytic methods have been studied thus, the reactions between N-Dpp imines and chiral ot-bromoenolates [49] (derived from Oppolzer s sultams Scheme 4.35) and between S-chiral sulfmylimines and achiral bromoenolates [50] (Scheme 4.36) have been reported. 

When the related saccharin derived sultam (R)-29 is converted into the (Z)-boron enolate and subsequently treated with aldehydes,. vy -diastereomers 30 result almost exclusively. Thus, the diasteromeric ratios, defined as the ratio of the major product to the sum of all other stereoisomers, surpass 99 1. Hydroperoxide assisted saponification followed by esterification provides carboxylic esters 31 with recovery of sultam 32106a. 

The same stereochemical result is obtained when the horyl cnolate 4, derived from sultam 1 is transmetalated by the addition of titanium(lV) chloride and subsequently reacted with aldehydes106g. 

The cthylaluminum dichloride promoted conjugate addition of organocoppcr-tributylphos-phine to the -substituted ( )-Ar-enoyl sultam 7 produced very high diastereoselectivity (88-96% de) and moderate yield (43-86%). The adducts were converted to the corresponding methyl ester 9 upon treatment with methoxymagnesium bromide or diazomethane 34. 

A7M aqueous solution of LiOII-H20 is added to a 0.35 M solution of the sultam 11 in THF and vigorously stirred at 65 "C for 3 — 5d. Evaporation in vacuo, trituration of the residue with CH2CI2 and evaporation of the dried extracts gave sultam R NH. Acidification of the CH2C12 insoluble residue with 2N aq HC1, saturation with NaCl, extraction with CU2C12 and evaporation of the dried (MgS04) extracts gave the crude carboxylic acid 12 which is purified by distillation. 

Asymmetric hefera-Diels-Alder addition of 1 -methoxybuta-1,3-diene to (2R)-N-pyruv-oyl-and (2R)-N-(phenylglyoxyloyl)bornane-10,2-sultam [69]... 

Kim B. H., Curran D. P. Asymmetric Thermal Reactions With Oppolzer s Camphor Sultam Tetrahedron 1992 49 293-318... 

Oligomers Oppolzer s camphor sultam (see also camphor derivatives) Organometallics Organosilicon Organosulfur Organozirconocenes Orthoquinodimethanes Oxabutadienes Oxanorbornadiene(s) Oxazinolactams Oxazinones Oxazoles... 

Starting from readily available substrates, a new one-pot procedure has been devised to prepare polycyclic lactams and sultams. 2-Pyrrolines 48 were obtained... 

This method is most successful when both the a and a position of the sulfone bear alkyl substituents. See also 17-20. Treating four-membered ring sultams with SnCl2 led to aziridine products via loss of SO2. 

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