Sulfamidates, cyclic

This class of aziridine-forming reaction includes the first reaction reported to afford aziridines. In 1888 Gabriel reported that aziridines could be prepared in a two-step process, by chlorination of ethanolamines with thionyl chloride, followed by alkali-induced cyclization [75]. Wenker subsequently reported that heating of 600 g of ethanolamine with more than 1 kg of 96 % sulfuric acid at high temperature produced P-aminoethyl sulphuric acid 282 g of it was distilled from aqueous base to give 23 g of aziridine itself, the first preparation of the parent compound in a pure condition [76]. Though there is no evidence to substantiate the hypothesis, the intermediate in these reactions is perhaps a cyclic sulfamidate (Scheme 4.51). 

The amide 33l06b and the cyclic sulfamide 34106c, both C2-symmetric, and the borneol derived amide 3510bd provide further ways to xyn-aldols with remarkable induced diastereoselectivity. 

Other types of HIV-1 protease inhibitors have also been prepared using microwave-promoted Suzuki reaction [37]. The symmetric cyclic sulfamide (3K,4S,5S,6it)-3,6-bis(phenoxymethyl)-2,7-bis[4-(2-thienyl)benzyl]-l,2,7-thi-adiazepane-4,5-diol 1,1-dioxide, for instance, was synthesized via cross-couphng of (3aS,4R,8it,8aS) - 5,7 - bis(4 - bromobenzyl) - 2,2 - dimethyl - 4,8 - bis-(phenoxymethyl) hexahydro [1,3] dioxolo [4,5 - d] [ 1,2,7 ] - thiadiazepine 6,6 - dioxide with 2-thienylboronic acid for 3 min at 45 W (Scheme 19). 

Cyclic sulfamides 326 serve as key intermediates in the synthesis of a series of potent and selective y-secretase inhibitors with potential for the treatment of Alzheimer s disease. 

An expeditious route to the cyclic sulfamide HIV-1 protease inhibitors of type 145 and 146 (tetrahydro-l,2,7-thiadiazepine 1,1-dioxide derivatives) from 141 and 142 hinges on palladium-catalysed amidation reactions. These reactions of 144 and 143 were microwave promoted and provided, after removal of the cyclic ketal protecting group, moderate to good yields of (145, 57%) and (146, 66%) for example with R = NHCOCH2-2-naphthyl <06T4671>. 

Intramolecular reductive cross-coupling of unsymmetrical dibenzylidene sulfamides 149 generated the corresponding cyclic sulfamides 150 in good yield (Scheme 23) <1996TL2859>. 

Aminoalcohols 196 react with Burgess-type reagents 197 to afford unsymmetrical cyclic sulfamides 198 (Equation 42) <2002AGE3866, 2004CEJ5581>. 

When sulfamate esters 114 are used as substrates, six-membered-ring formation is favored, and results in the selective formation of 1,2,3-oxathiazinane-2,2-dioxide heterocycles 115.251 Nevertheless, five-membered cyclic sulfamidates could be obtained when no alternative cyclization was possible. 1,3-Amino alcohols and related /2-amino acids are thus readily accessible from the same simple alcohols 113 by converting them into sulfamates 114 (Equation (90)). Furthermore, in comparison to the carbamate reaction (Scheme 9), the sulfamate substrates have... 

The sulfamate ester variant of this chemistry has already been shown to be a very powerful protocol for the syntheses of 1,3-amino alcohols and related /3-amino acids (Equation (90)), as well as iminium ion equivalents (Equation (91)). The further showcases of this chemistry are the total syntheses of the bromopyrrole alkaloids, manzacidins A and C (Scheme 13).234 The cyclic sulfamidate 129 was obtained diastereospecifically from sulfamate 128 using intramolecular rhodium-catalyzed G-H insertion. It was then found to react with sodium azide in NfN-dimethylformamide at room temperature after introduction of the Boc-activating group to afford the 1,3-diamino precursor 130 in 78% yield over 3 steps. Four subsequent manipulations afford the target structure 131. 

Choquette et al. investigated the possibilities of using a series of substituted sulfamides as possible electrolyte solvents (Table 12). These compounds are polar but viscous liquids at ambient temperature, with viscosities and dielectric constants ranging between 3 and 5 mPa s and 30 and 60, respectively, depending on the alkyl substituents on amide nitrogens. The ion conductivities that could be achieved from the neat solutions of Lilm in these sulfamides are similar to that for BEG, that is, in the vicinity of 10 S cm Like BEG, it should be suitable as a polar cosolvent used in a mixed solvent system, though the less-than-satisfactory anodic stability of the sulfamide family might become a drawback that prevents their application as electrolyte solvents, because usually the polar components in an electrolyte system are responsible for the stabilization of the cathode material surface. As measured on a GC electrode, the oxidative decomposition of these compounds occurs around 4.3—4.6 V when 100 fik cm was used as the cutoff criterion, far below that for cyclic carbonate-based solvents. 

Reaction of [ F]fluoride anion on cyclic precursors (epoxides [220], cyclic sulfonates [221], cyclic sulfamidates [222, 223]) is an efficient strategy for the stereospecific synthesis of )3- F-fluoroalcohols or )9- F-fluoroaniines. Typical examples are shown in Scheme 54. 

Carbolithium compounds of moderate reactivity open the O—C bond of cyclic sulfate esters or cyclic sulfamidates to produce new C—C links, as shown, for example, in equation 112 for a chiral cyclic sulfamidinate and 2-lithio-l,3-dithiane (380a). More reactive organolithium species, such as n-BuLi and PhLi, yield mixtures of products, probably due to attack on the S atom of the sulfonamido group too °. 

Cyclic sulfamides (14) exhibit enhanced acidity versus their acyclic counterparts by about 4 pA units. The sulfur d-orbitals and/or the added ring strain may be responsible <84JCS(P2)l85l>. 

In the case of the thiazolidinedioxides (38), the increased acidity of the cyclic sulfamide determines the reactivity. Metallation (NaH) occurs at N—H producing an anion which is readily alkylated <93TL4705>. Treatment with triphenylphosphine produces a stable betaine which can be used to couple alcohols and acids in a variant of the Mitsunobu reaction <94JOC2289>. 

Thiadiazole oxides and reduced forms are readily prepared via [4 -h 1] cyclizations (Table 4). The reagents employed for this purpose are thionyl chloride, sulfuryl chloride, sulfur tetrafluoride, N,N -bis(p-toluenesulfonyl)sulfur diimide, cyclic diimides, pentafluoroethyliminosulfur difluoride and sulfamide. 

An improved method for the synthesis of a-fucosyl (l- 3)-3-thio-glycoside (65 c) involved the nucleophilic displacement of a cyclic sulfamidate derived from allosamine (67). The regioselective opening of (67) with (30b) led to (65c) in good yield (Scheme 21) [51]. 

Iodine reacts with sulfuryl chloride in the presence of aluminum chloride as catalyst-forming iodine chlorides. Sulfuryl chloride reacts with anhydrous ammonia yielding a series of sulfamides of the general formula NH2S02(NHS02)kNH2, where n > 0. A cyclic compound of the formula... 

In the same vein as the cyclic sulfate activation of diols, cyclic sulfamidates have been prepared from 1,2- and 1,3-amino alcohols for the purpose of activating the carbinol toward nucleophilic attack [85-88]. (S)-Prolinol [85], A-benzyl serine t-butyl ester [86], and 2-(2-hy-... 

The general method for the synthesis of cyclic sulfamides including the respective l,l-dioxo-3,6-dihydro-thiadia-zepines 46 from 44 has been described <2003T6051> (Scheme 5) in which the yield of the final step was 75%. 

Burgess reagent, (methoxycarbonylsulfamoyl)triethylammonium hydroxide, usually used for the dehydration of secondary or tertiary alcohols, was successfully employed in the formation of cyclic sulfamidates from the corresponding epoxides. It was further shown that the same reaction with aromatic epoxides resulted in the formation of seven-membered ring systems, for example, 57 (Figure 23) <2003SL1247>. 

The cyclic sulfamidate (79) reacts with a host of neutral and anionic sulfur nucleophiles to give an excellent yield (84-99%) of product (80).127 1,8-Diazabicyclo[5.4.0] undec-7-ene (DBU) was added to ionize the neutral nucleophiles. All the reactions proceed with an inversion of configuration at the quaternary carbon even when tertiary alkanethiols are used. Therefore, since a kinetic study showed that the reaction is first order in both the nucleophile and (79), an S 2 mechanism applies. 

An intramolecular version of such reactions is also known (00TL7365, 01T7899). In particular, A-(3-nitroaryl)allylsulfonamides 273 are converted by DBU and MgCl2 in DMSO into a mixture of peri- cyclic sulfamides 274 and their A-oxides 275 (Scheme 79). 

Dithiazoles investigated are given in Figure 1(a) these are 1,2,3-dithiazolium cations 1, 1,2,3-dithiazolyl radicals 2, l,2,3-dithiazole-3-ones 3 and related compounds 4, their 2-oxides 5. 1,2,3-Oxathiazoles have been obtained and investigated in the form of their A-oxides (Figure 1(b) and named as cyclic sulfamidates 7 and 8 and sulfimidates 6, 9, and 10. 

Cyclic sulfamidates can be converted into / i-arninoalcohols (Equation 27). The deprotection protocol (1 1 mixture of aqueous HCl/dioxane, room temperature) had sufficient scope for general synthetic utility several sulfamidates were readily deprotected giving aminoalcohols under these conditions. High yields were observed in all examples, despite relatively large variations in the reaction time that is necessary to complete conversion <2002AGE834>. 

Surprisingly, when the cyclic sulfamidate derived from iV-acetyl-D-allosamine 126 was treated with different nucleophiles, three types of products were formed by nucleophilic displacement of sulfamide at C-3 and proton abstraction at C-2 or C-4 (Scheme 18) <1997T5863>. Potassium acetate and sodium azide effectively provide regioselective ring opening to afford thio and azido derivatives 127. When oxy-anions were used as nucleophiles, elimination was the main pathway (sugars 128 and 129). 

The regiospecific nucleophilic displacement of 1,2-cyclic sulfamidates 130 with methyl thioglycolate or a-amino esters 130 can be accompanied by lactamization (thermal, base mediated, or cyanide catalyzed) to give thiomorpho-lin-3-ones and piperazin-2-ones 131 (Scheme 19) <20030L811>. If malonate esters, phosphonate-stabilized esters, or aryl-substituted enolates were used as nucleophiles in this reaction, trisubstituted pyrrolidines were obtained in high yield <2004OL4727>. 

Sodium imidazolate (Naim), sodium cyanide, and other reagents smoothly deacetylate the cyclic 2,3-sulfamidate 126 (Equation 32) <1997T5863>. 

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