Cyclam alkylation

Tabushi and Fujiyoshi have prepared alkylated cyclam derivatives for the purpose of suspending these systems from a polymer backbone. They have utilized a malonic ester alkylation reaction followed by cyclization and reduction to accomplish this end. ... 

Strategies for selective partial alkylation of cyclam have been developed and Ni11 complexes of the variously substituted ligands prepared.1489 In a series of tetra-A-alkylated cyclams, Ni11 incorporation was only observed for smaller substituents such as Me, Et, and Pr, while no... 

It is well-established that electroreduced nickel(I) complexes of cyclam and a variety of substituted cyclams add oxidatively to alkyl halides to give alkylnickel(III) complexes in organic solvents,251,276 the lifetime of the carbon-nickel bond governing the overall behavior of the system. However, it was shown that [Ni (tmc)]+ (one-electron reduced form of complex (17) tmc= 1,4,8,11-teramethyl 1,4,8,11-tetraazacyclotetradecane) reacts with alkyl chlorides in aqueous alkaline solution in a one-electron process.277,278... 

Ni-cyclam, Ni(CR), or Ni(tet a) can be used efficiently as catalyst in DMF, and in the presence of NH4CIO4 as proton source [71-74]. Ni species generated electrochemically react rapidly with organic halides to generate alkyl, alkenyl, or aryl radicals which add intramolecularly to a double or triple bond, then leading to cyclopentanoids (Table 7, entries 3-7a). 

Nickel-cyclam and related complexes can also be used though previous reports indicated that the turnover of Ni/(tet a) in acetonitrile is low [85]. The process has now been reinvestigated to show that Ni/(tet a) can been used in catalytic conditions (2%) in DMF containing NH4CIO4 as proton source to perform the alkylation of unsaturated esters, ketones, or nitriles (Table 9) [86]. Yields are good if the terminal carbon of the double bond is not substituted (Ri = H). 

Bis-iV-alkylated complexes of Me2-9 and Me2-ll, as well as the tetra-methylated Ni(II)cyclam (NinTMC) derivatives, have been synthesized by the deprotonation of secondary amines followed by alkylation (34, 47,48). When EtI or other alkyl halide with /3-hydrogen was added to the deprotonated Ni(II) complex of cyclam or 11, HX elimination occurred instead of SN2 reaction. Therefore, ethylene gas was produced instead of -ethylated complex formation when EtI was added to the deprotonated complex of cyclam or 11. However, in the case of 8, bis- -ethylated Ni(II) complex was isolated. This may be because HX elimination is slower than SN2 reaction. The - -alkylated Ni(II) complexes of 9 (Me2-9 and Et2 9) and Me2-ll were stable against ligand dissociation in acidic aqueous solutions. The -alkylated complexes were dealkylated when the complexes were heated in aqueous solutions (34, 47). 

The introduction of N-alkyl substituents to the secondary nitrogens of 9 and 11, as well as cyclam, results in the shift of Amax values to... 

The Ni(I) complex of tetramethylated cyclam, [Ni(TMC)]+, generated from the corresponding Ni(II) complex by electrochemical or photochemical methods, reacts with alkyl halides (RX) (133,140-143). It is a radical reaction, generating R transients and/or Ni-alkyls, which then decay to form alkanes, alkenes, and dimeric or cyclic organics. 

Coordinated secondary amines can also be alkylated, but only after deprotonation by a strong base generates a suitable nucleophile. Work on rhodium(III) complexes of ethylenediamine12 has been extended to nickel(II) complexes of various fully saturated macrocycles such as cyclam (Scheme l).13,14 The methylated cyclam complex is kinetically inert, unlike the isomer with all four methyl groups on the same side of the ring, which is obtained on reaction of the preformed tetramethyl cyclam with nickel ions. 

In addition to the charge control over the reaction discussed above, there is also a marked element of conformational control over alkylation reactions. This is seen clearly in the methylation of the nickel(n) complex of the tetraaza macrocyclic ligand, cyclam (Fig. 5-32). Reaction of the nickel complex with methylating agents allows the formation of a A, A V",A "-tetramethylcyclam complex. In this product, each of the four nitrogen atoms is four-co-ordinate and tetrahedral, and specific configurations are associated with each. Of the four methyl groups in the product, two are oriented above the square plane about the nickel, and two below it. 

Nitrogen-containing macrocycles are highly complementary for first row transition metals as in the examples shown in Section 1.6. Common azamacrocycles include cyclen ([12]ane-N4) and cyclam (3.45) and many have a history that significantly pre-dates the crown ethers. Unlike the crown ethers which do not have donor atom substituents, the binding constants of azamacrocycles such as cyclam are greatly affected by N-alkylation. Alkylated amines are significantly more basic than ammonia, for... 

Reductive radical cyclization and tandem radical addition/cyclization reactions catalyzed by Ni(II) complexes, such as Ni(cyclam)(C104)2 98a, were studied starting in the 1990s by Ozaki s group [128]. The reaction conditions are applicable to alkyl and aryl halides bearing suitable positioned olefin units. Iodides and bromides can be used in some cases even aryl chlorides were successfully applied. The field was reviewed recently, and thus only more recent results are summarized here [19, 20]. 

Adamantyl)thiacalix[4]arene was synthesized either by condensation of p- 1 -adamantyl)-phenol with sulfur in the presence of base or alkylation of p-//-thiacalix[4]arene with adamantanol in F3CCO2H <02TL5153>. A new macrotricyclic ligand with an N4S2 donor set has been synthesized from cyclam it was shown to encapsulate lithium and transition metal ions <02CC170>. 

A small library of aryl- and alkyl-linked cyclams, which were further substituted in different positions with -(CH2)4C02H pendant arms, was synthesized to get AZT-bis(cyclams) conjugates (AZT = azidothymidine) C1998TL853, 1999JME229>. 

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