Tosylate coupling

The mesylate-tosylate in the framework of the pyranose derivative reacted with lithium acetylide-ethylenediamine complex to give the seven-membered sultone (13) in 98% yield, as a result of displacement of a tosylate coupled with deprotonation at the mesylate producing a nucleophile and then ring formation (Scheme 6) <81CJC260>. 

The primary amine of an amino acid as its tosylate salt can be protected by coordination with a crown ether. The protection scheme was sufficient to allow the HOBt/DDC coupling of amino acids. The crown is removed by treatment with diisopropylethylamine or KCl solution. 

Efficient coupling between a chiral 3-phenylpropionamide enolate and (S)-glyci-dyl tosylate was achieved in a practical route to the HIV-1 protease inhibitor L-735-524 [68b]. 

Early development of the homo-coupling reactions of aryl halides involves the use of stoichiometric amounts of air-sensitive Ni(0) complexes.54 The reaction could also be realized with a catalytic amount of Ni(0) complexes formed in situ when a stoichiometric amount of Zn was present. Besides aryl iodides, tosylates,... 

Deoxy-5 -fluoroadenosine (911) and the analogs 910, 912, 913 were prepared by coupling of 5-deoxy-5-fluoro-D-ribofuranose and 6-chloro-purine. 2, 5 -Dideoxy-5 -fluoroadenosine (914) was prepared through a displacement reaction of the corresponding 5 -0-tosyl precursor with fluoride (BU4NF in DMF). The carbocyclic nucleosides 915 and 916 have been prepared and their antiviral activities evaluated. 

However, the Buchwald-Hartwig reaction with NHCs as hgands is not limited to palladium. Nickel has also been successfully employed in this catalytic amination. In situ procedures have been described for the coupling of aryl chlorides [163] and tosylates [164] and, more interestingly, anisoles [165]. The use of well-defined Ni(0) catalysts has also been studied [166] (Scheme 6.49). 

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

Another excellent catalyst for coupling is a mixture of CuBr-S(CH3)2, LiBr, and LiSPh. This catalyst can effect coupling of a wide variety of Grignard reagents with tosylates and mesylates and is superior to Li2CuCl4 in coupling with secondary sulfonates.64... 

NiCl2[P(c-C6Hn)3]2 is an effective catalyst for coupling aryl tosylates with arylboronic... 

The reaction conditions were optimized to afford clean coupling of enol tosylate 32 using only a slight excess of amide 24 (1.05equiv) at 100 °C, 5mol% Pd2(dba)3/ dppb catalyst, and a toluene/tert-amyl alcohol solvent system. Even under the harsh reaction conditions required for complete conversion of the tosylate (100 °C, 20 h) no detectable E/Z isomerization was seen, providing further proof that the hindered nature of the enamide aids stability to isomerization. Treatment of the mixture with activated carbon (Darco KB-B) at the end of the reaction followed by isolation of the product by crystallization, afforded enamide 22 in 92% isolated yield. 

The 1 R,6R,7R,8S-as-fused structure and conformation of 102 were elucidated on the basis of their NMR spectroscopic data. The observed formation of only one sulfonium salt in this cyclization reaction was remarkable in that either sulfur atom might have been expected to participate in tosylate displacement. The H NMR spectrum of salt 102 shows a large three-bond scalar coupling of 10.6 Hz between H-6 (5 = 4.736) and H-7 (5 = 4.606) this indicates that they have an almost antiperiplanar relationship. The equatorial orientation of H-6 and the 3C6 conformation of its six-membered cycle are consistent with the strong NOEs observed between H-7 and both H-2axja and and... 

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