Palladium‐Catalyzed Amination of 3,5‐Dihalopyridines – a Convenient Route to New Polyazamacrocycles

Abstract

Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthdayPd-Catalyzed amination of 3,5-dibromo-and 3,5-dichloropyridine (1a and 1b, resp.) with linear polyamines 2 leads to the formation of a new family of pyridine-containing macrocycles 3 with an −exo×-oriented pyridine Natom (Schemes 1 and 2). The dependence of the macrocycle yield on the nature of the halogen atom, the length of the polyamine chain and C/N atom ratio, and the composition of the catalytic system is studied. The synthesis of mono-and bis(5-halopyridin-3-yl)-substituted polyamines 4, 5, 8, 9, and of 3,5-bis(polyamino)-substituted pyridines 6 is described (Schemes 3 and 4), and the use of these compounds as intermediates on the way to the macrocycles 7, 16, and 18 with larger cavity (−cyclodimers× and −cyclotrimers×) is demonstrated (Schemes 5 ± 10).Introduction. ± In the last 15 years, substantial interest was evoked by the synthesis and coordination properties of different polyazamacrocycles which possess a pyridine moiety in the macrocyclic ring [1 ± 13]. This pyridine fragment strongly influences the thermodynamic properties and the complexation kinetics by increasing the conformational rigidity of the ligand and by changing its basicity. Thus, the basicity was shown to decrease in such macrocycles as compared to corresponding saturated molecules like tetraazacycloalkanes. The metal complexes of the pyridine-containing macrocycles are usually less stable than those of tetraazacycloalkanes while the first demonstrate higher formation rates. In all such macrocycles incorporating pyridine, N-atoms are linked to the aromatic ring via one CH 2 or CH group. To date, only one macrocycle containing Natoms directly linked to the pyridine ring has been reported [14]. This compound was obtained by the reduction of the corresponding diamide formed in the reaction of pyridine-2,6-diamine with diacyl dichloride under high-dilution conditions. Macrocycles of this type containing a 3,5-disubstituted pyridine moiety are yet unknown. In our recent work, we have proposed a simple one-pot approach to polyazamacrocycles with an −endo×-position 1 ) of the pyridine N-atom derived from 2,6-dibromopyridine by using Pd-mediated amination with linear polyamines [15]. Therefore, it is of importance to elaborate a simple way to their isomers with an −exo×-oriented

Facile Synthesis of New Polyazamacrocycles by the Pd-Catalyzed Amination of 3,3'-Dibromobiphenyl

“…A two-neck flask equipped with a magnetic stirrer and a condenser, flushed with dry argon, was charged with 3,3'-dibromobiphenyl (1) (0.5 mmol, 156 mg), absolute dioxane (25 ml), Pd(dba) 2 (24 mg, 8 mol%) and BINAP (28 mg, 9 mol%). The mixture was stirred for 2 min, then appropriate polyamine 2 (0.5 mmol) and t BuONa (1.5 mmol) were added, and the reaction mixture was refluxed for 24 h. After cooling to the ambient temperature and filtration of the precipitate dioxane was evaporated in vacuo and the residue was chromatographed on silica gel using a sequence of eluents: CH 2 7,10,13,24,27,.1 2,6 .1 14,18 .1 19,23 ] octatriaconta-1(35),2(38), 3,5,14(37), 15,17,19(36), 20,22,31, 7,10,13,16,3.1.1 2,6 ]pentacosa-1 (24) ,2(25),3,5,20,22- h e x a c o n t a -1 ( 6 1 ) , 2 ( 6 6 ) , 3 , 5 , 1 7 ( 6 5 ) , 1 8 , 2 0 , 2 2 ( 6 4 ) , 23,25,37(63) …”

“…[16] To the moment, there are no literature data on the synthesis of biphenyl-based macrocycles which employs catalytic bond formation between aromatic and aliphatic parts of the molecule. In recent years we have accumulated experience on the application of the Buchwald-Hartwig amination [17] in the synthesis of polyazamacrocycles starting from various dihaloarenes [18][19][20][21] and we investigated this approach for the construction of biphenyl-based macrocycles.…”

Contribution of I. P. Beletskaya in the Twentieth Year Successful Russian-French Cooperation in Catalytic Syntheses

“…Thus the elaboration of the synthesis of pyridine-based macrocycles was conducted using 2,6-and 3,5-dihalopyridines and a wide range of polyamines. [24][25][26][27] Corresponding macrocycles were obtained in yields ranging from near trace to 42 % depending on the polyamine used, and cyclic dimers with larger cavity sizes were also synthesized. This investigation was helpful for the further synthesis of valuable macrocycles based on 6,6'-diamino-2,2'-bipyridine.…”

Synthesis of polyaza macrocycles by palladium-catalyzed amination of 1,2-dibromobenzene and 2-bromo-1,3-dichlorobenzene

“…This approach was applied to the synthesis of polyaza and polyazapolyoxa macrocycles containing 1,3-disubstituted benzene [17], 2,6-and 3,5-disubstituted pyridine [18,19], and 1,8-and 1,5-disubstituted anthracene and anthraquinone fragments [20]. Macrocycles having anthracene and anthraquinone fragments attract specific interest, for their electronic absorption spectra lie in the visible region, while anthracene derivatives show strong luminescence which makes them promising as molecular sensors.…”