Tosylamide derivatives

The synthesis of 11 (an analogue of 7 in which its 12-membered cyclen had been replaced by 14-membered cyclam rings) was reported in 1998 using the tri-N-tosylamide derivative of cyclam and l,3,5-tris(bromomethyl)benzene as precursors [24], The trinuclear Hg(II) derivative was shown to selectively recognise and bind a tripodal tris(histidine) ligand in which the three (S)-histidines are 12 A apart. The system was seen as a model for peptide recognition. 

Aftalion and Proctor71 examined the mass spectra of several tosylamides, derived from cyclic and aromatic amines, in the attempt to draw some generalizations on the electronic or conformational requirements which rendered the molecular ion prone to loss of S02. 

If the aromatic moiety of a cinnamylamine derivative has an ort/io-halogen substituent, 1,2-dihydroquinoline would be obtained yia the subsequent S Ar reaction. In the presence of catalytic amounts of tosylamide, MBH adduct 603 was rearranged to the thermodynamically more stable tosylamide derivative, which then could be easily subjected to nucleophilic aromatic substitution reaction at the ortho position, giving 1,2-dihydroquinoline 605 in 81% yield. Furthermore, using DBU as a base, elimination of p-toluenesulfinic acid afforded quinoline 606 in 69% yield (Scheme 4.178). However, interestingly, Xn-substituted MBH adducts 607 were directly converted into quinolines 608 in a one-pot reaction in moderate yields. The discrepancy between 604 and 607... 

Negishi coupling of jV-ethynylzinc tosylamides derivatives 92, prepared from 1,1-dichlorovinylamide 91 with aryl iodides in the presence of Pd2(dba)3 and triphenylphosphine afforded A-aryl and A -alkyl arylynamides 93. ... 

Similar reactions have been carried out on acetylene. Aldehydes add to alkynes in the presence of a rhodium catalyst to give conjugated ketones. In a cyclic version of the addition of aldehydes, 4-pentenal was converted to cyclopen-tanone with a rhodium-complex catalyst. In the presence of a palladium catalyst, a tosylamide group added to an alkene unit to generate A-tosylpyrrolidine derivatives. ... 

Hydroaminomethylahon of alkenes [path (c)j wiU not be considered [12]. This review deals exclusively with the hydroaminahon reaction [path (d)], i.e. the direct addition of the N-H bond of NH3 or amines across unsaturated carbon-carbon bonds. It is devoted to the state of the art for the catalytic hydroamination of alkenes and styrenes but also of alkynes, 1,3-dienes and allenes, with no mention of activated substrates (such as Michael acceptors) for which the hydroamination occurs without catalysts. Similarly, the reachon of the N-H bond of amine derivatives such as carboxamides, tosylamides, ureas, etc. will not be considered. 

Miller and co-workers have reported the use of thiazolylalanine-derived catalyst 65 to render the aldehyde-imine cross-coupling enantioselective [56]. The authors comment on the time sensitivity of this transformation and found that racemization occurs when the reaction goes to complete conversion. Electron-deficient aldehydes are the most efficient couphng partners for various tosylamides leading to the corresponding products 66, 68, and 69 (Scheme 8). 

Intramolecular bicyclization of tosylamide with alkynyliodonium salt (see Scheme 31), developed by Feldman and co-workers (95JA7544), is also applicable to the synthesis of A-tosylpiperidine derivatives related to polycyclic alkaloids (Eq. 40). Examples leading to seven-membered rings have also been reported. 

Iron salts (e.g. FeCls) have been identified as new catalysts for intramolecular hydroamination. A number of olefinic tosylamides underwent the reaction at 80 °C to form the corresponding the N-tosylpyrrolidine derivatives in good yield.63 The same salt can also catalyse Markovnikov addition of electron-rich arenes and heteroarenes to styrenes, giving rise to 1,1-diarylalkanes at 80 °C.64... 

A similar intermolecular cyclization was recently utilized in the synthesis of highly substituted dihydropyrrole derivatives [133 -135]. In a specific example, the addition of pentadienyltosylamide derivatives 177 to propynyl(phenyl)iodo-nium triflate initiates a sequence of transformations that furnishes the complex, highly functionalized cyclopentene-annelated dihydropyrrole products 178 in moderate yields with complete stereoselection (Scheme 66). Under similar reaction conditions, the isomeric isoprene-derived tosylamide 179 reacts with propynyl(phenyl)iodonium triflate to give azabicyclo[3.1.0]hexane 180 as the final product [134]. 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at —78°C to afford homoallylic alcohols with high enantioselectivity (eq 13). On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions. 

Bis(hydroxymethyl)-l,3-dithiole-2-thione 454 could be easily transformed into the dibromide 207 with phosphorus tribromide <1998CC361>. The reaction of the latter with tosylamide afforded the dihydropyrrole derivative 456, which was dehydrogenated with DDQ to produce 457. Treatment of 207 with -butylamine in the presence of cesium carbonate led to A - -butyldihydropyrrole 455 (Scheme 65) <2000JOC5794>. 

Sulfonyl groups can also be utilized to reduce the basicity of amino functions. Inter- and intra-molecu-lar cyclizadon using bifunctional tosylamides have been widely utilized in the preparation of macrocy-clic polyamines (Scheme 13). Trifluoromethanesulfonamide and its derivatives can also be used in the preparation of primary and secondary amines. ... 

Defunctionalizations. The cyano group of a-cyano ketones and esters and the sulfonyl residue of tosylamides and gem-bissulfones are removed by LN. Carbanions derived in this way can be alkylated. 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the thiazolylalanine-derived catalyst 191 for asymmetric intramolecular Stetter reaction of a,P-unsaturated esters <05CC195>. However, these cyclizations proceed only in moderate enantioselectivities and yields even under optimized conditions. Thiazolium salt 191 has been used successfully for enantioselective intermolecular aldehyde-imine cross coupling reactions <05JA1654>. Treatment of tosylamides 194 with aryl aldehydes in the presence of 15 mol% of 191 and 2... 

Triarylbismuthine A -tosylimides react with benzaldehyde, benzoyl chloride and phenyl isocyanate to give A -tosylimine, A-tosylamide and A -tosylurea derivatives, respectively [91CL105] (Section 5.5.2.3). The imides oxidize secondary and benzylic alcohols to carbonyl compounds, sometimes accompanied by the concurrent formation of a diaryl(A -tosylamino)bismuthine [96JCR(S)24] (Section 5.2.4). When treated with acetic acid, the imides are converted to the corresponding triarylbismuth diacetates and sulfonamides (Scheme 3.9). 

Sulfonamide acridinium derivatives have been utilized as signal labels for sensitive immunoassays because of their stability and high chemiluminescence yield. Two acridinium derivatives, N-sulfopropyl N-tosylamide acridinium [Acr or Acr(spcp)] and N,N-disulfopropyl N-p-(3-carboxypropyl)phenylsulfonamide acridinium [Acr(spsp)], were used in our conjugates.4 Their structures and chemiluminescence reaction mechanism are illustrated in Fig 1. 

Rearrangements. Allylic sulfoximines undergo Pd-catalyzed rearrangement to give the tosylamides. The reaction furnishes optically active amine derivatives from chiral sulfoximines. 

Finally, halogen-containing allylic tosylamides have been employed in the annulation of internal alkynes to generate 2,3-dihydropyrrole derivatives (Eq.50) [73]. 

An increase in the electron deficiency of the sulfonates, by replacement of a mesyl by a trifluoromethanesulfonyl group, induces an increase in the proportion of alkanes versus alcohols in the product mixture. Thus deoxysugars can be obtained in good yield, either by photolysis of the triflate derivatives in aqueous HMPA or reduction by sodium in liquid ammonia. The detosylation reactions of arenesulfonates and arenesul-fonamides do not always require PET processes. When the photolysis is carried out in solvents such as EtjO or MeOH, the alcohol can be recovered in high yields from arenesulfonates while a mixture of amine and ammonium tosylate is usually obtained from tosylamides. A mechanistic study of the reaction indicated that the bond initially cleaved is different in sulfonates and sulfonamides (Scheme 3). ... 

The highly soluble imidoiodanes 473-476, which are derived from ortfto-alkoxyiodobenzenes, were synthesized in two simple steps starting from readily available 2-iodophenol ethers 468 (Scheme 2.135) [634]. In the first step, iodides 468 were oxidized by peracetic acid to form diacetoxyiodo derivatives 469-472 the structures of products 469 and 472 were established by X-ray analysis. In the second step, diacetates 469-472 were converted into imidoiodanes 473-476 by treatment with tosylamide under basic conditions in methanol. Compounds 473-476 are relatively stable at room temperature and can be stored for several weeks in a refrigerator. They also have good solubility in dichloromethane, chloroform and acetonitrile (e.g., the solubility of 472 in dichloromethane is 0.25 g mC ) [634]. 

Similarly to A-(2-iodylphenyl)acylamides, the tosyl derivatives of 2-iodylaniline 503 and 2-iodylphenol 505 were prepared by the dimethyldioxirane oxidation of the corresponding 2-iodophenyltosylamides 502 or 2-iodophenyl tosylate (504) (Scheme 2.143) and isolated as stable, microcrystalline products [665], A singlecrystal X-ray diffraction analysis of tosylamide 503 (R = Me) revealed a pseudocyclic structure formed by intramolecular I—O interactions between the hypervalent iodine center and the sulfonyl oxygens in the... 

Aminocarbonylation of A -4-pentenyl-A -methylurea (146) gave 147 smoothly in the presence of PdCl2, CuCl2 and O2 [61]. Aminocarbonylation of the unsaturated diamine derivative 148 is chemoselective. In the presence of sodium acetate and methyl orthoformate, aminopalladation of the tosylamide took place selectively to Erfford 150 via 149. On the other hand, selective reaction of the carbamate occurred to give 151 in the absence of sodium acetate [62],... 

Recently, palladium-catalyzed asymmetric allylic substitution of an activated cyclohexenol derivative has allowed two enantioselective syntheses of (—)-galantha-mine (75) (234,235). Both approaches rely on the enantioselective preparation of the same tricyclic intermediate, which is subsequently converted to the alkaloid via stereocontrolled transformations the most efficient of which comprised stereoselective allylic oxidation of the cyclohexene moiety (Scheme 5). The same methodology allowed the synthesis of (—)-codeine and (—)-morphine (236). The same group had earlier reported the synthesis of (-l-)-pancratistatin following a related strategy (237). Use of a tosylamide as the nucleophile in the displacement of an activated aryl-cyclohexenol derivative enabled the preparation of a chiral intermediate which... 

Subsequently, Balan and Adolfsson et al. employed chiral quinuchdine derivatives as catalysts in the asymmetric one-pot three-component aza-MBH reaction of aryl aldehydes, tosylamide and alkyl acrylates or acrylonitrile. A sterically non-hindered tricyclic derivative of quinidine (141) was the most efficient catalyst in transferring its chiral information. High conversions were ensured by using a catalytic amount of titanium isopropoxide and by the addition of molecular sieves (4 A). The corresponding adducts 218 and 219 were obtained in good yields with up to 74% ee (Scheme 1.84). ... 

The domino process involves an aza-Morita-Baylis-Hillman/reduction sequence. A series of tosylamide-functionalized coumarin derivatives 145 were assembled with high diastereoselectivity concerning the newly created contiguous carbon centers. 

---