Practical preparation of N-(1-alkynyl)sulfonamides and their synthetic utility in titanium alkoxide-mediated coupling reactions

Aliphatic and aromatic sulfonamides were alkynylated with 1-bromo-1-alkynes in the catalytic presence of CuI to give N-(1-alkynyl)sulfonamides in good to excellent yields. Racemization of optically active sulfonamides was not observed during this alkynylation. The acetylene-titanium complexes generated from the resultant N-(1-alkynyl)sulfonamides and Ti(O-i-Pr)₄/2 i-PrMgCl underwent regio-, olefinic stereo-, and diastereoselective addition to aldehydes to give virtually single allyl alcohols. Alternatively, inter- or intramolecular coupling reaction between N-(1-alkynyl)sulfonamides and another acetylene or olefin with the above titanium alkoxide reagent generated the corresponding titanacycles, hydrolysis of which furnished stereo-defined (sulfonylamino)dienes or cyclic compounds.     

Fukuyama-Mitsunobu alkylation in amine synthesis on solid phase revisited: N-alkylation with secondary alcohols and synthesis of curtatoxins

The Fukuyama-Mitsunobu amination strategy has emerged as an efficient means of N-alkylation of peptides and sulfonamides, as well as a method for synthesis of polyamines on solid phase. Here, an array of reagent combinations for solid-phase alkylation with secondary alcohols was examined in various solvents. The classical reagents DEAD-PPh₃ as well as DEAD-PEt₃ proved applicable for a single alkylation step. Sharply dropping yields in successive alkylation steps were identified as the most serious limitation of the use of Fukuyama-Mitsunobu reaction in SPS of polyamines using primary and in particular secondary alcohols.     

Asymmetric addition of diethylzinc to benzaldehyde catalyzed by novel chiral C2-symmetric tetrakis(sulfonamide)–titanium(IV) complexes

A series of chiral C₂-symmetric tetrakis(sulfonamides) 3a–f, 4a–f were prepared and employed as ligands for titanium(IV) complexes in the asymmetric addition of diethylzinc to benzaldehyde. The chiral secondary alcohols were obtained in high yields and in moderate enantioselectivities.     

Reactions of n-sulfinyl-p-toluenesulfonamide with alcohols

N-Sulfinyl p-toluenesulfonamide (1) reacted with triaryl- and diarylmethanols to give predominantly N- substiuted sulfonamides and SO₂ presumably via carbonium ion intermediates. When carbonium ion forming alchols, such as t-BuOH and Ph₂C(Me)OH, were used the predominant products were alkenes and p- toluenesulfonamide. Allytic alcohols afforded N- substiuted sulfonamides along with dienes andp-toluenesulfonamide. Alcohols which could not predictably give relatively stable intermediate carbonium ions, gave either dialkyl sulfites or dialkyl eithers, along with p-toluenesulfonamide. In one case, namely with 9-phenylfluorenol the 1:1 adduct with 1 (an amidosulfite) was isolated. A mechanism for the reactions is proposed.     

Fluorous scavenger for parallel preparation of tertiary sulfonamides leading to secondary amines

Alkylation of secondary sulfonamides by alkyl halides or alcohols (Mitsunobu reaction) is an efficient method for secondary amines preparation. However, its application to parallel chemistry is often difficult due to partial reaction. In this Letter, we propose a fluorous technique to bypass this problem. Thus, o-nitrobenzenesulfonamides were prepared and alkylated in parallel (Fukuyama method) with various alkyl halides or alcohols. Depending on the nature of the alkyl halide or alcohol, this step remained incomplete. A reactive fluorous alkyl iodide was then used to trap the unreacted sulfonamide allowing for a rapid and efficient fluorous solid-phase extraction (FSPE). Some examples of the isolated tertiary sulfonamides were converted in parallel to the corresponding secondary amines with good purity.     

Gold versus silver-catalyzed amination of allylic alcohols

Direct substitution of the hydroxy group in allylic alcohols by different nitrogenated nucleophiles is performed using low loadings of cationic gold(I) or silver salts as catalysts. Sulfonamides, carbamates and aromatic amines can be used as nucleophiles. Comparative studies between the best catalysts, cationic (triphenylphosphite)gold(I) complex and silver triflate, demonstrate that the former catalyst shows, in general, better performance than silver, working at lower loadings, in shorter reaction times and at lower temperatures. Representative allylic alcohols are used giving good γ-regioselectivity, specially in the case of penta-1,4-dien-3-ol and (E)-1-phenylbut-2-en-1-ol affording the corresponding allylic sulfonamides with total regio and stereoselectivity by a hydroamination mechanism. In the case of crotyl alcohol and (E)-4-phenylbut-3-en-2-ol mainly and exclusively α-substituted sulfonamides were obtained, respectively, by a cationic mechanism.     

Kinetics of the reactions of tert-butanol with C2-C5 alcohols on sulfo cation exchangers

The kinetics of etherification of tert-butanol with aliphatic alcohols on gel KU-2×8 and macroporous KU-23 sulfo cation exchangers was studied. The first order of reaction with respect to tert-butanol and the -CSO₃H groups of a catalyst was established. The activation energy of the process observed on KU-2×8 was 60–95 kJ/mol. It was shown that the etherification of tert-butanol on KU-2×8 occurred in a surface layer. The reactivity of primary alcohols introduced into the reaction with tert-butanol increased with their molecular weights (C₂–C₅). The rate of reaction with secondary alcohols was lower than that with primary alcohols.     

Chemo- and diastereoselective Bi(OTf)3-catalyzed benzylation of silyl nucleophiles

The direct alkylation of silyl enol ethers with para-methoxybenzylic alcohols or their corresponding acetates was efficiently catalyzed by Bi(OTf)₃ in CH₃NO₂ as the solvent. The reaction provided the α-benzylated carbonyl compounds in high yields after short reaction times using 1-2.5 mol % of the catalyst. Benzylic acetates other than para-methoxybenzylic acetates also underwent the reaction. High facial diastereoselectivities were observed with acetates derived from chiral α-branched para-methoxybenzylic alcohols. In addition, a catalytic reduction with Et₃SiH as the reducing agent is reported.     

Use of the Mitsunobu reaction in the synthesis of orthogonally protected α,β-diaminopropionic acids

Orthogonally protected α,β-diaminopropionic acids have been synthesised in good yields by the reaction of N-trityl l-serine esters with N-substituted sulfonamides under Mitsunobu reaction conditions (DEAD, PPh₃, THF). The best isolated yields were obtained when N-Boc p-toluenesulfonamide was used as the nitrogen nucleophile precursor in the Mitsunobu reaction. Subsequently, the N-trityl group was efficiently replaced with the more stable allyloxycarbonyl (alloc) group.     

Regioselective addition of pyrrole to N-tosyl imines in the presence of Cu(OTf)2

The Cu(OTf)₂ catalysed reaction of pyrrole with N-tosyl imines gives pyrrole sulfonamides in high yields. The addition reaction takes place regioselectively at C(2) of the pyrrole. The procedure is simple and does not require anhydrous conditions.     

A novel and efficient solvent-free and heterogeneous method for the synthesis of primary, secondary and bis-N-acylsulfonamides using metal hydrogen sulfate catalysts

Some metal hydrogen sulfates were used as acid catalysts in the N-acylation of different sulfonamides using carboxylic acid chlorides and anhydrides as acylating agents under both heterogeneous and solvent-free conditions. Al(HSO₄)₃ and Zr(HSO₄)₄ were found to have the highest activity and catalyze the reactions efficiently to furnish the primary N-acyl sulfonamides (RCONHSO₂R′), secondary N-acylsulfonamides (RCONR″SO₂R′) and bis-N-acylsulfonamnides [RCO(SO₂R′)N-R″-N(SO₂R′)COR] in good to high yield. The mild reaction conditions, inexpensive and low toxicity of catalysts and easy work-up procedure make this method attractive.     

Highly Efficient One-Pot Synthesis of N-Alkyl Sulfonamides from Alcohols Using N-(p-Toluenesulfonyl) Imidazole (Tsim)

Abstract

A facile and efficient method for one-pot synthesis of N-alkyl sulfonamides from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this protocol, treatment of various potassium sulfonylamide salts and alcohols in the presence of TsIm and triethylamine in refluxing DMF furnishes the corresponding N-alkyl sulfonamides in good to excellent yields. This methodology is highly efficient for reaction of various structurally diverse primary and secondary alcohols as well as potassium sulfonylamides. Also, the density functional theoretical calculations are employed to mechanistically study this protocol.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

Cross coupling of 3-bromopyridine and sulfonamides (RNHSO2R·R = H, Me, alkyl; R = alkyl and aryl) catalyzed by CuI/1,3-di(pyridin-2-yl)propane-1,3-dione

N-(3-Pyridinyl)-substituted secondary and tertiary sulfonamides have been synthesized in good to excellent yields by the reaction of 3-bromopyridine with primary and secondary alkyl and aryl sulfonamides (MeSO₂NH₂, MeSO₂NHMe, TolSO₂NH₂, TolSO₂NHMe, 1,3-propanesultam, and 1,4-butanesultam), catalyzed by CuI (20 mol %) and 1,3-di(pyridin-2-yl)propane-1,3-dione (20 mol %) with K₂CO₃ (200 mol %) in DMF (0.17 M for ArBr) at 110-120 °C over 36-40 h. 2-Bromopyridine, 4-bromopyridine, and a wide variety of substituted phenyl bromides can also be successfully coupled with sulfonamides under these reaction conditions.     

tert-Butylnitrite as a convenient and easy-removable oxidant for the conversion of benzylic alcohols to ketones and aldehydes

The oxidation of primary and secondary benzylic alcohols was achieved by using tert-butyl nitrite (t-BuONO) as a stoichiometric oxidant. Various substrates were effectively converted into the corresponding ketones or aldehydes in good to excellent yields. The reaction presumably proceeded by a nitrosyl exchange and a subsequent thermal decomposition of benzylic nitrites. This process would realize an oxidation of alcohols with oxygen in theory by combining with a reproduction of alkyl nitrites from NO and alcohols under an O₂ atmosphere. In addition, almost pure oxidized products were readily obtained by simple evaporation of the reaction mixtures since t-BuONO produced only volatile side products.     

Dynamic kinetic resolution of secondary alcohols with a readily available ruthenium-based racemization catalyst

An easy to handle and stable racemization catalyst for secondary alcohols is obtained by an in situ mixture of readily available [Ru(cymene)Cl₂]₂ with chelating aliphatic diamines. Optimization of the reaction revealed that N,N,N′,N′-tetramethyl-1,3-propanediamine as ligand racemizes aromatic alcohols completely within 5 h. This easy to handle and stable catalytic system is combined with a lipase-catalyzed resolution to provide an efficient dynamic kinetic resolution of secondary alcohols.     

Boron trichloride as an efficient and selective agent for deprotection of tert-butyl aryl sulfonamides

A fast, mild and selective method for deprotection of tert-butyl aryl sulfonamides utilizing BCl₃ as deprotection reagent has been developed. A variety of tert-butyl aryl sulfonamides used under these conditions gave the corresponding primary sulfonamides in high yields. The method does not cleave methoxy groups and prevents incorporation of tert-butyl groups onto electron-rich aromatic rings.     

Reactions of polyhalomethanes with olefins catalyzed by copper complexes with aromatic amino alcohols

Copper complexes with amino alcohols structurally similar to ephedrin (1-phenyl-3-(N-methylamino)propan-1-ol and 1-phenyl-2-(N-methylamino)ethanol) are catalytically very active in the free-radical addition of CCl₄ and CBr₄ to linear alk-1-enes. These amino alcohols themselves are initiators of radical addition reactions, and, in the reaction with CBr₄, they are more active than the metal complexes. In the presence of the amino alcohols, as distinct from classical radical initiators, the reaction is highly selective and affords an addition product. An analysis of kinetic equations and the data obtained for the reaction involving CHCl₃ suggest that the amino alcohols and the corresponding metal complexes are involved in different ways in the addition of CCl₄ and CBr₄ to linear alk-1-enes.     

Transition metal free oxidative esterification of alcohols with toluene

Using Bu₄NI as the catalyst and tert-butyl hydroperoxide as the oxidant, direct esterification of alcohols with toluene derivatives was achieved. Mechanistic investigations indicate that the alcohols are sequentially oxidized to aldehydes, carboxylic acids, and then to benzyl esters. Bu₄N⁺ functions as a phasetransfer reagent and iodide catalyzes the reaction.     

Synergistic Ag(I)/nBu4NBr-catalyzed fixation of CO2 to β-oxopropyl carbonates via propargylic alcohols and monohydric alcohols

Chemical fixation of carbon dioxide under mild reaction conditions e.g. atmospheric pressure and low temperature depends upon the ability of catalyst. Herein, a synergistic catalytic scheme of silver sulfadiazine/ⁿBu₄NBr was described for the three-component reaction of propargylic alcohols, CO₂, and monohydric alcohols. This catalytic system was demonstrated effectively to provide β-oxopropyl carbonates in excellent yields (up to 99% yield with 5?mol% catalyst). The method tolerated a wide scope of propargylic alcohols and monohydric alcohols under atmospheric CO₂ pressure and solvent-free conditions. The excellent catalytic performance was attributed to the synergistic catalysis confirmed by the careful experiments.     

Dimethylaluminum halide induced reactions of formaldehyde with alkynes. Synthesis of α-allenic alcohols and Z-3-chloroallylic alcohols

The CH₂O·Me₂AlCl complex reacts with terminal alkynes to give α-allenic alcohols via a formal ene reaction and Z-3-chloroallylic alcohols via a stereospecifically syn Friedel-Crafts addition.