Bis-sulfonamide intermediate

A mass spectrometry technique - ESI(- -)-MS(/MS) - has been used to probe solution-phase DABCO-catalysed aza-MBH reactions of A-sulfonylimine (24) with methyl acrylate to give aza-adduct (25). A unique bis-sulfonamide intermediate (26) was intercepted, which - if central to the process - requires a revision of the generally accepted mechanism. A new mechanistic proposal does fit better with some features of aza-MBH reactions. ... 

Monitoring the DABCO-catalysed aza-MBH reaction of CH2=CHC02Me with ArCH=NTs (Ar = 4-MeOCgH4) by ESI(- -)-MS(/MS) spectrometry allowed an interception of the unique bis-sulfonamide intermediate (201). ... 

Recently, EberUn and Coelho have investigated the mechanism of the aza-MBH reaction via ESI-MS(/MS) spectrometry and proposed a rational mechanism [19]. They monitored the DABCO-catalyzed aza-MBH reaction of methyl acrylate 2 (R = CO2CH3) with imine 12 by ESI-MS(/MS) spectrometry and intercepted the key intermediates 13 and 15 and also a unique bis-sulfonamide intermediate 14. Based on their results, they proposed the mechanistic cycle for the aza-MBH reaction depicted in Scheme 31.5. 

Several catalytic systems have been reported for the enantioselective Simmons Smith cyclopropanation reaction and, among these, only a few could be used in catalytic amounts. Chiral bis(sulfonamides) derived from cyclo-hexanediamine have been successfully employed as promoters of the enantioselective Simmons-Smith cyclopropanation of a series of allylic alcohols. Excellent results in terms of both yield and stereoselectivity were obtained even with disubstituted allylic alcohols, as shown in Scheme 6.20. Moreover, this methodology could be applied to the cyclopropanation of stannyl and silyl-substituted allylic alcohols, providing an entry to the enantioselective route to stannyl- and silyl-substituted cyclopropanes of potential synthetic intermediates. On the other hand, it must be noted that the presence of a methyl substituent at the 2-position of the allylic alcohol was not well tolerated and led to slow reactions and poor enantioselectivities (ee<50% ee). ... 

The Corey allylation system based on a chiral bis(sulfonamide) auxiliary was put to use with success in a number of synthetic efforts, including the total synthesis of the anticancer agent leucascandrolide (Scheme 13). Chiral reagent 152 is added to an achiral aldehyde, 3-(/ -methoxybenzyloxy)propanal, affording intermediate 153 in high stereoselectivity. The latter is transformed into a pyranyl aldehyde, which is subjected to a second allylation (this time, a doubly diastereoselective addition) en route to the completion of leucascandrolide. 

In early studies of these reactions, the turnover efficiency was not always high, and stoichiometric amounts of the promoters were often necessary to obtain reasonable chemical yields (Scheme 105) (256). This problem was first solved by using chiral alkoxy Ti(IV) complexes and molecular sieves 4A for reaction between the structurally elaborated a,/3-unsaturated acid derivatives and 1,3-dienes (257). Use of alkylated benzenes as solvents might be helpiul. The A1 complex formed from tri-methylaluminum and a C2 chiral 1,2-bis-sulfonamide has proven to be an extremely efficient catalyst for this type of reaction (258). This cycloaddition is useful for preparing optically active prostaglandin intermediates. Cationic bis(oxazoline)-Fe(III) catalysts that form octahedral chelate complexes with dienophiles promote enantioselective reaction with cyclopentadiene (259). The Mg complexes are equally effective. 

Weinreb and coworkers have examined some reactions of dihydrothiazine imines and have developed a new approach to vicinal diamines using these intermediates. Their method is outlined in Scheme 18. Cycloaddition of ( . )-2,4-hexadiene with the tosyl bis-imine gives a 1.1 1 mixture of epimeric dihydrothiazine imines (140) and (144). Subsequent transformations of these adducts took two different courses. In one, adduct (140) could be opened to allylic sulfilimine (141) which underwent a stereoselective 2,3-sigmatropic rearrangement to sulfenamide (142) (c/. equation 54). Desulfurization of (142) yielded E)-threo vicinal sulfonamide (143). Adduct (144), which presumably exists in conformation U45), suffers a unique stereoselective transannular 2,3-sigmatropic rearrangement to thiadiazolidine (146) which can also be converted to bis-sulfonamide (143). 

Scheme 14.138). A ligand accelerating effect has been observed with the titanium bis (sulfonamide)imido complex. This complex can promote the reaction at room temperature with reaction rate comparable to that of its precursor, supporting the hypothesis of a catalytically active titanium imido intermediate. 

Sulfenamides arc usually oxidized to sulfonamides tns(tnfluorotnetliane-sulfenyl) and bis(tnfluoromethanesulfenyl)arnineare converted to the corresponding sulfonamides by sodium hypochlorite at 20 tor 3 h m 61 and 92% yield, respecbvely [111] Oxidation of pentafluorobenzenesulfendimde by manganese dioxide yields a sulfinamide intermediate that can be trapped [772] (equabon 102)... 

When optically active allylic alcohol 6a and propargylic alcohol 6p were reacted with amides 2c and 2f, only racemic products 7ac, 7af, and 7pf were obtained (Scheme 2). The results suggested a mechanism through the formation of a carbe-nium intermediate. The observed racemization can also be ascribed to the reversibility of the present reaction. The result shown in Scheme 3 indicated that the reaction is reversible under the reaction conditions. When 7af was treated with 5 mol% of Bi(OTf)3 and KPF6 and 1 equiv of carbamate 2c, a mixture of 7af (28%) and 7ac (68%) was recovered after 1 h. The result suggested that Bi(OTf)3/KPF6 cleaved the C-N bond in 7af derived from sulfonamide 2f, and that 7ac is thermodynamically more stable than 7af. We assume that the desiccant (Drierite) had a beneficial effect on the reactions of substrates shown in Tables 10-12 because of the observed reversibility of the present reaction. In this reaction, the possibility... 

Access to this type of compound is illustrated in Scheme 30 by the preparation of retro-sulfonamide tripeptide Boc-Pro-Leuijt[NH—S02]Gly-NH2(78). The two false termini used are the prochiral gem-diamino analogue of Leu and sulfoacetic acid. Amide to amine conversion according to Hofmann, carried out on the dipeptide Boc-Pro-Leu-NH2 (76) with iodobenzene l,l-bis(trifluoroacetate) gave the gem-diamino derivative 77. Coupling of the resulting gem-diamino derivative with methyl (chlorosulfonyl)acetate, followed by amida-tion of the intermediate methyl ester, afforded the desired pseudopeptide 78J1341 Full experimental details have not yet been reported. 

The treatment of various sulfides with Phi = NTs in the presence of cuprous triflate leads to the corresponding N-tosylsulfimides (N-tosylsulfilimines) 21 [30]. The presence of the chiral bis(oxazoline) ligand 22 in the reaction medium results in coordination of the copper(III)-nitrene intermediate, L Cu(III) = NTs, and enables the enantioselective production of 21 (Scheme 12). Similar copper-catalyzed reactions of allylic sulfides with Phi = NTs lead to formal insertion of the NTs group into the carbon-sulfur bond of the substrates, and proceed via a [2,3]-rearrangement with allylic inversion, to give sulfonamides 23 [30]. 

Cossement et al. [9] s)nithesized the enantiomers of l-(p-chlorobenzhy-diyl)-4-(p-methylphenyl)sulfonyl piperazine 3 and used it as an intermediate for fhe preparation of buclizine 6 and other histamines. The enantiomers of (+)- and (—)-l-(p-chlorobenzhydryl)-4-(p-foluene sulfo-nyl)piperazine 3 were prepared and converted by hydrolysis to the enantiomers of (+)- or (—)- of p-chlorobenzhydryl piperazine 4. Compound 3 was prepared by refluxing p-chlorobenzhydrylamine 1 with N-bis-2-chloroethyl-p-toluene sulfonamide 2 with ethyl diisopropylamine. Reaction of p-ferf-bufylbenzyl chloride 5 wifh p-chlorobenzhydryl piperazine 4 gives buclizine 6. 

---