Benzyl sulfonamide

N-benzyl-sulfonamides are cleaved under "relatively mild conditions" with potassium alkoxide (19). 

Although Helmchen et al. showed that asymmetric iridium-catalyzed allylic substitution could be achieved, the scope of the reactions catalyzed by iridium complexes of the PHOX ligands was limited. Thus, they evaluated reactions catalyzed by complexes generated from [lr(COD)Cl]2 and the dimethylamine-derived phosphoramidite monophos (Scheme 8) [45,51]. Although selectivity for the branched isomer from addition of malonate nucleophiles to allylic acetates was excellent, the highest enantiomeric excess obtained was 86%. This enantiomeric excess was obtained from a reaction of racemic branched allylic acetate. The enantiomeric excess was lower when linear allylic acetates were used. This system catalyzed addition of the hthium salts of A-benzyl sulfonamides to aUylic acetates, but the product of the reaction between this reagent and an alkyl-substituted linear aUylic acetate was formed with an enantiomeric excess of 13%. 

Primary benzenesufonamides have been notoriously difficult to protect. Theodore S. Widlanski of Indiana University has now found (Tetrahedron Lett. 2004,45, 8483) that while N-benzyl sulfonamides such as 1 are resistant to hydrogenolytic debenzylation, the easily-prepared Boc derivative 2 is smoothly debenzylated. Brief exposure of 3 to trifluoroacetic acid then gives the primary sulfonamide 4. 

The combination of an aryl- or alkylsulfonamide, 3 equiv. PhI(OAc)2 and substoichiometric I2 is able to promote C-H animation of simple hydrocarbons in the absence of any metal catalyst [120]. These reactions are best performed neat (10-fold excess of substrate relative to RS02NH2) at 50°C and appear to operate with reasonable selectivity to give benzylic sulfonamide products. Over-oxidation to the sulfonylimine is noted in some cases. A proposed reaction mechanism posits the intermediacy of a sulfonamidyl radical, formed from the AModosulfonamide. This pathway parallels in many ways the mechanism invoked for the Hofmann-Loffler-Freytag process. 

In the latter case, only 1% of benzylic sulfonamide 169 was observed resulting from the cleavage of the nonbenzyhc C—bond. A similar substrate 170 was hydrogenolyzed in 99% yield using transfer hydrogenation conditions with formic acid as the hydrogen source (Scheme 51). ... 

In 2011, inspired by Cozzi and Cheng, Tian and co-workers [130] developed asymmetric Sjvl a-alkylation of ketones and aldehydes with V-benzylic sulfonamides... 

A-Benzylic sulfonamides, Ar Ar CHNHTs, a-alkylate aldehydes, and ketones (R CH2C0R ) to give products, Ar Ar CH CH (R )-COR, in up to 84% ee, through C-N bond cleavage, using TFA and a chiral imidazolidinone as catalysts. 

Furthermore, N-benzylic sulfonamides can generate stabilized carbocations under conditions of organocatalysis. This was reported for the reactions of ketones and aldehydes in the presence of catalytic amounts of chiral imidazolidin-4-ones [51]. 

Aryl bromides were also perfluoroethylated under these conditions [205] The key to improved yields was the azeotropic removal of water from the sodium perfluoroalkylcarboxylate [205] Partial success was achieved with sodium hepta-fluorobutyrate [204] Related work with halonaphthalene and anthracenes has been reported [206 207] The main limitation of this sodium perfluoroalkylcarboxylate methodology is the need for 2 to 4 equivalents of the salt to achieve reasonable yields A trifluoromethylcopper solution can be prepared by the reaction of bis(tri-fluoromethyl)mercury with copper powder in /V-methylpyrrolidone (NMP) at 140 °C [208] (equation 138) or by the reaction of N-trifluoromethyl-A-nitro-sotnfluoromethane sulfonamide with activated copper in dipolar aprotic solvents [209] This trifluoromethylcopper solution can be used to trifluoromethylate aro matic [209], benzylic [209], and heterocyclic halides [209]... 

Tosyl azide reacts differently to give sulfonamide derivatives 134). The morpholine enamine from dibenzylketone (196) for instance reacted with tosylazide to give 197 and phenyldiazomethane (198), which was trapped with acetic acid giving benzyl acetate 134). 

Ceric ammonium nitrate (CAN), CH3CN, H2O, it, 12 h, 96% yield. Benzylamides are not cleaved under these conditions. Some of the methods used to cleave the benzyl group should also be effective for cleavage of the PMB group. Ceric ammonium nitrate is also used to cleave the PMB group from a sulfonamide nitrogen. ... 

In 2004, Alterman et al. used a microwave-assisted Ullmann-type protocol for the synthesis of N-(f-butyl)-3-[4-(lH-imidazol-l-yl)benzyl]-5-isobutylthiophene-2-sulfonamide (Scheme 106) [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloro-formate finally gave the target compound for biological evaluation as selective angiotensin II AT2 receptor agonist. The IH-imidazole derivative, however, showed only a low affinity for the AT2 receptor (Ki value > 10 p,M). 

Sulfonamides are relatively acidic and their anions can serve as nitrogen nucleophiles.64 Sulfonamido groups can be introduced at benzylic positions with a high level of inversion under Mitsunobu conditions.65... 

A-Protected amines were assembled on solid-phase via sulfonamide-based handle 58 (Scheme 27) [67]. Tertiary sulfonamides were generated upon reaction with allylic, benzylic and primary alcohols under Mitsu-nobu conditions. Secondary amines were released from the support using mild nucleophilic conditions such as treatment with thiophenol and potassium carbonate. 

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

BAm = benzylamine BE = benzyl ether BMI.Tf2N = bis(trifluoromethane)sulfonamide of l-n-butyl-3-methylimidazolium CH = cyclohexane ... 

The reaction of pentafluorophenyl isocyanate with thiadiazole 8 in acetonitrile at room temperature gave 5-penta-fluorophenylureido-l,3,4-thiadiazole-2-sulfonamide 105 (Equation 31) <2004JME2796>. Similarly, 2-amino-l,3,4-thia-diazole 37 reacts with benzyl isocyanate in dry THF to afford the l,3,4-thiadiazol-2-yl urea 106 in 94% yield (Equation 32) <1999JME1525>. 

ALDEHYDES FROM ALLYLIC ALCOHOLS AND PHENYLPALLADIUM ACETATE 2-METHYL- 3-PHENYLPROPIONAL-DEHYDE, 51, 17 ALDEHYDES FROM AROMATIC NITRILES p-FORMYLBENZENE-SULFONAMIDE, 51, 20 ALDEHYDES FROM 2-BENZYL-4,4,6-TRIMETHYL—5,6-DIHYDRO-l, 3-(4H)-OXAZINE 1-PHENYLCYCLO-PENTANECARBOXYALDEHYDE, 51,... 

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