Amino sulfonamide

The same pattern of activity is maintained in a closely related analogue. Condensation of amino-sulfonamide 201 with aldehyde 202 affords the saturated heterocyclic system (203) oxidation with silver nitrate leads to the antihypertensive agent pazoxide (204). 49... 

Compounds of type (543 R = Ar) have also been synthesized by reacting the tv-amino-sulfonamide (547) with chloroacetyl chloride and subsequent cyclization of (548). 

Routes to 3,4-dihydro-2/7-1,2-benzothiazine dioxides (253) include the cyclization of aminosulfonic acids (252) or cyanosulfonamides (254). 2,4-Dihydro-1H-2,1 -benzothiazine dioxides (256) are normally prepared by thermolysis of the sodium sulfonates (255) or amino sulfonamides (257)... 

The Curtius rearrangement provides a route to carbamates of a-amino sulfonamides (Scheme 25). 108 Reaction of the ethyl ester of an a-bromo acid 52 with Na2S03 yielded the sodium salt of the corresponding sulfonic acid 53. Treatment of 53 with PQ5 afforded the sulfonyl chloride 54 which on reaction with an amine gave the sulfonamide 55. The latter... 

Scheme 25 Formation of Carbamates of a-Amino Sulfonamides via Curtius Rearrangement 1 1...

Because sulfonamides are generally more stable towards enzymatic degradation than amides, the preparation of oligosulfonamides as peptide mimetics has been thoroughly investigated. The synthesis of a-aminosulfonamides has not been successful, probably because of the instability of this class of compound [261], For the more stable P-amino sulfonamides and vinylogous a-aminosulfonamides (3-amino-l-pro-pene-l-sulfonamides), however, suitable synthetic routes have been developed. Unfortunately, the preparations of the required monomers are not as easy as those of related amino acid derived monomers (Figure 16.27). 

A mechanically stirred suspension of crude amino-sulfonamide hydrochloride salt (26.4 g, 73 mmol) in water (70 mL) was heated at 90°-95°C until all of the solid dissolved. To the hot solution was added activated carbon (Darco KB, 0.26 g), and the mixture stirred for 15 min at 90°-95°C. The mixture was filtered hot (85°-90°C) through a well-washed bed of filter aid (SuperCel). The filter cake was washed with boiling water (9 mL). The filtrate and cake wash were combined, and the product allowed to crystalize as well-stirred solution was cooled to 60°C. The mixture was stirred for 1 h at 60°C, or until the product had convened to the thermodynamically more stable hemihydrate crystal form. The mixture was then slowly cooled to 3°C, and then stirred for 1 h at this temperature. The mixture was filtered cold, using the mother liquors to rinse the cake. The product was air-dried, then dried in vacuo (100 mBar, nitrogen sweep, 45°-50°C) to constant weight. Yield 24.2 g (92% yield 59% overall yield from hydroxysulfone) of pure aminosulfonamide hydrochloride salt (dorsolamide) as a white crystalline solid. HPLC 99.9 area % (254 nm), 99.6 wt % vs an external standard, >99% (4S,6S) as the N-TFA derivative. Specific Rotation a589 =-17.1° (c=1.00, H20). MP 238°C. 

Amino sulfonamides are readily condensed with formaldehyde to produce 3,4-dihydro-2//-l-thia-2,4-diazine 1,1-dioxides application affords 219, which was studied as a potential thrombin inhibitor <2003BML1441> while benzo derivative 220 was used as a precursor to potentially selective inhibitors of tumor necrosis factor-a-converting enzyme <2003JME1811>. 

Ring expansion of 3-alkyl-2-(iV-cyanoimino)thiazolidine 1-oxides initiated by trifluoroacetic anhydride produces 5,6-dihydro-2//-l-thia-2,4-diazin-3(4//)ones (Section 9.05.10). 2-Aminobenzothiazoles react with chlorosulfonylacetyl chloride to form fused 4//-l-thia-2,4-diazine 1,1-dioxides (Section 9.05.9.2.1) and cationic 2-methylthio-l,3-diazines react with similar sulfonyl chlorides to produce 3-(methylthio)-2//-l-thia-2,4-diazines (Section 9.05.9.2.2). Condensing 2-amino sulfonamides with formaldehyde leads to the 3,4-dihydro-2//-l-thia-2,4-diazine 1,1-dioxide system (Section 9.05.9.2.3). 

It is interesting that the condensation between electron-rich phenol, amine, and a chiral a -A, A -dibenzylamino aldehyde has been reported to be temperature sensitive, with high syn selectivity at high reaction temperatures while high anti selectivity is observed at low reaction temperatures. Similar to the Aldol Condensation, the Mannich reaction can be promoted or catalyzed by either acid or base. Furthermore, different protic acids or Lewis acid alone or in combination with a different chiral ligand or auxiliary group is used to enhance the stereoselectivity of the Mannich reaction, such as proline, (,S )-amino sulfonamide, BINOL phosphate," At-spiro chiral quaternary ammonium bromide, and dodecylbenzenesulfonic acid" as well as Lewis acids, such as Cu(OAc)2, CuC104, " Cu(OTf)2-chiral diamine complexes,... 

The cross-aldol reaction between enolisable aldehydes (donor aldehydes) and nonenolisable aldehydes (acceptor aldehydes) is known to be catalysed by L-proline and the related amine catalysts, giving antz -aldol adducts. For instance, the cross-aldol reaction of propanal with 4-nitrobenzaldehyde gave the corresponding anti-dXdoX adduct with excellent diastereo- and enantioselectivity (Scheme 17.4). ° The reaction catalysed by an amino sulfonamide (5 )-3, on the other hand, gave the unusual q n-aldol product as the major diastereomer. ... 

In analogy with the above-mentioned amine-catalysed aldol reactions, our binaphthyl-based amino sulfonamide catalysts showed unique reactivity and selectivity in the asymmetric Mannich reaction of aldehydes. For instance, the Mannich reaction of propanal with an a-imino ester catalysed by (S)-3 gave the antr-Mannich adduct as a major diastereomer, while the syn-Mannich adduct was obtained in the proline-catalysed reaction first reported by the Barbas group (Scheme 17.8). ... 

The binaphthyl-based amino sulfonamide (5 )-3 and an amino acid (5 )-8 were also applied for the asymmetric aminojylation with nitrosobenzene (Scheme 17.14). In the presence of either (5 )-3 or (5 )-8, the aminoxylation of aldehydes proceeded smoothly, and subsequent reduction with sodium borohydride gave 2-aminoxyl alcohols with good to excellent enantioselec-tivity. In each case, (5 )-3 and (5 )-8, which have identical axial chirality, gave opposite enantiomers as major products. 

FIGURE 4.4. (a) Transition state of the axially chiral amino sulfonamide-catalyzed asymmetric Mannich reaction, (b) Transition state of the chiral 5-methyl-3-pyrrolidinecarboxylic acid-catalyzed enantioselective Mannich reaction. 

The iminium activation strategy with the trifunctional chiral primary amine 28, which was used in the y-selective conjugate addition of y-butenolides (Scheme 28), also proved highly effective for promoting reaction with the y-butyrolactam (Scheme 32, first line) [52]. Although various chiral diamines, amino thioureas, and amino sulfonamides were evaluated during the optimization study, none of these catalysts gave rise to impressive levels of diastereoselectivity. Eventually, a bulky acid additive, such as the protected tryptophan derivative (V-Boc-L-Trp-OH),... 

A rare chemo- and stereo-selective cross-aldol between aliphatic aldehydes, catalysed by proline and an axially chiral amino sulfonamide, links a simple aldehyde with an a-chloroaldehyde the chemoselectivity arises from the steric instability of 0 the enamine derived from the haloaldehyde. (g)... 

A simple amino sulfonamide (54) - easily prepared from L-phenylalanine -catalyses direct aldols of aldehydes with ketones in brine, giving anf/-aldols in up to 97% ee. ... 

A yyn-selective cross-aldol reaction of aldehydes with f-butyl glyoxylate and glyox-amide gives densely functionalized products in up to 99% ee, using a BINAP-derived axially chiral amino-sulfonamide catalyst. ... 

A classic reduction of ketones is the Meerwein-Pondorf-Verlay reaction, in which a ketone is reduced by an alcohol in an equilibrium process catalyzed by aluminum oxides. A modern version of this overall transformation that occurs by a different mechanism is the "transfer hydrogenation" of ketones and imines using alcohols as reagent. For years, little progress on this reaction had been made with transition metal complexes. However, a breakthrough was made when Noyori discovered that ruthenium complexes of amino sulfonamides (Figure 15.15) and amino alcohols catalyze... 

Scheme 2.19 Aldolisations of ketones with aldehydes catalysed by P-amino sulfonamide.

Few chiral secondary amine organocatalysts have been applied to the asymmetric aldol reaction, in 2008. As an example, Maruoka and Kano have designed a binaphthyl-based amino acid, which was applied to induce the asymmetric aldolisation of both acyclic and cyclic ketones with both aliphatic and aromatic aldehydes performed in DMF. ° Remarkable results were obtained in general with enantioselectivities of up to 99% ee for either cyclic or acyclic ketones, which led to the <2 n-products (Scheme 2.41). Furthermore, these authors have used a closely related binapthyl-based amino sulfonamide to promote the cross-aldol reaction between aldehydes, which yielded the corresponding syn products in moderate to high yields (71-91%) and diastereoselectivities (72-90% de) combined with excellent enantioselectivities (94-99% ee). 

Excellent enantioselectivities have also been observed by Maruoka et al. by using several other chiral secondary amines as organocatalysts for the anti-Mannich reaction between various aldehydes and A -protected hnines including a-imino esters. Therefore, the involvement of a chiral binaphthyl-based amino sulfonamide as the organocatalyst allowed a series of UM/i-Mannich products to be obtained from both iV-Boc-protected imines and A -PMP-protected a-tmino esters by reaction with aldehydes. As shown in Scheme 3.12, excellent yields and enantioselectivities (97-99% ee) were observed along with moderate to high anti diastereoselectivities of up to 90% de. 

Scheme 3.12 Mannich reactions catalysed by binaphthyl-based amino sulfonamide.

The same authors have designed novel chiral pyrrolidine-based amino sulfonamides, which were applied to promote a n -Mannich reactions of A/-PMP-protected a-imino esters with aldehydes, giving comparable results to those obtained with the binaphthyl-based amino sulfonamide catalyst. However, these novel pyrrolidine-based amino sulfonamides were found to be capable of promoting a //-Mannich reactions between A/-PMP-protected a-imino esters and a range of cyclic as well as acyclic ketones with excellent yields, enan-tioselectivities combined with moderate to high diastereoselectivities of up to 90% de (Scheme 3.13). 

In addition, an asymmetric aminoxylation reaction of aldehydes by nitroso-benzene catalysed by a binaphthyl-based chiral amino sulfonamide was reported by Maruoka et As shown in Scheme 4.9, combinations of excellent yields... 

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