Sulfonamides reductive cleavage

This procedure illustrates a general method for the preparation of amines by reductive cleavage of sulfonamides by hydrobromic acid in the presence of phenol.9 The present synthesis makes 1,3-dihydroisoindole readily accessible and is superior in certain respects to the other two practical methods of preparation. Thus the method here described is shorter and gives a higher overall yield than the three-step synthesis of Neumeyer,7 and obviates the special apparatus and careful control required by the electrochemical process of Dunet, Rollet, and Willemart.4... 

Primary ally lie amines1 In the presence of this catalyst, allylic chlorides or acetates react with sodium p-toluenesulfonamide in THF/DMSO (80 20) to form the corresponding allylic sulfonamide in 60-85% yield. The products are converted into primary allylic amines on reductive cleavage (sodium naphthalenide). 

Reductive cleavage of sulfonamides.2 Sodium naphthalenide can be used for this reaction, but it does not cleave mesyl amides of primary and dialkyl amines. A wide variety of sulfonamides is cleaved with potassium and dicyclohexyl-18-crown-6. 

The reduction of sulfonamides has been investigated in methanol [154, 246], DMF [247,249], and MeCN [248] the reductive cleavage of A -tosyl amino acids and peptides has been studied in methanol at pH 11 at different electrodes lead was the preferred material for deprotection [256,257]. 

Reductive cleavage. Certain cyclic sulfonamides suffer double cleavage of C—S and N—S bonds, but an A -benzyl group is more labile. 

C.viii. Sulfonamides. Reduction of sulfonamides does not give an alcohol and an amine. Primary sulfonamides resist reductive cleavage with LiAlH4 secondary sulfonamides are cleaved, but the reaction requires... 

A synthesis of Agelastatin A by Weinreb and co-workers featured the use of a 13 bis[2-(trimethylsilyl)ethylsuifonyl] sulfodiimide 137 2 as an enophile in a two-step allylic amination reaction [ heme 8.137]. The initial ene reaction produced a dipolar intermediate 1373 that underwent a [2,3] Sigmatropic shift to afford the SES-protected allylic amine derivative 137,4. Reductive cleavage of the N-S bond followed by cleavage of the Boc group with trifluoroacetic acid gave the sulfonamide 1373 in 50-60% overall yield. Final deprotection of the SES group with TBAF returned the desired amine 137,6 in 90% yield. 

Reductive cleavage of the sulfonamide group in (64 R = p-Me-C6H4S02) with potassium in liquid ammonia affords the potassium salt of 4Ef-l,4-dihydrooxazocine <84AG(E)309>. This salt reacts with... 

Reductive Cleavage of Phthalides and Sulfonamides. 3-ArylphthaUdes can be readily cleaved reductively by means of TMSI (in situ generated) to give corresponding 2-benzyIbenzoic acids (eq 57) or 2-(2-thienylmethyl)benzoic acids. " ... 

These curious chemical entities led us to study the reactivity of potassium anion (K ) generated from K/crown ether/diglyme (or Et20, THF) system and toluene radical anion from K/crown ether/toluene system. The effectiveness of the former system for reductive cleavage of sulfonamide was reported elsewhere- -. In the present paper, reductive defluorination with the latter system is reported- -. ... 

With these solid supports in hand, we turned our attention to a new route to the synthesis of our target molecule 23 (Scheme 8). The tricky reductive amination should be replaced by an N-alkylation. To that end, bromoacetic acid is attached to 24c using DIC and Hiinig s base followed by the nucleophilic substitution with the corresponding benzy-lamine in DMSO/toluene (1 1), which can be easily monitored by the Beilstein test, followed by sulfonamide formation in DCM using N-methylmorpholine as base. For the final cleavage, 2% TFA in DCM is used and the resulting solution is filtered in a saturated NaHCC>3 solution to neutralise the acid before evaporation of the solvent. The crude product was then crystallised from ethyl acetate/heptane to yield the desired product in 27% yield overall and 99A% HPLC purity (see Table 4). 

Treatment of 70 with 1,3-propanedithiol and -Pr2NEt effected both the cleavage of the sulfonamide and the reduction of the azide to afford 71. 

To further illustrate the diversity of hydrolytic opening reactions, we turn our attention to an isothiazole ring as found in the antipsychotic agent ziprasidone (11.129). This drug is subject to various reactions of oxidation and reduction, but also undergoes hydrolytic cleavage of the C=N bond of the isothiazole ring. Evidence for this reaction was afforded by detection of radioactive metabolite 11.130, a sulfonamide, in the urine of patients dosed... 

Reduction of Sulfonamides Cyclization Promoted by Af-Tosyl Group Cleavage... 

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