Palladium-Catalyzed Amination in the Synthesis of Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety

Abstract

P o l y a z a m a c r o c y c l e s C o n t a i n i n g a 1 , 3 -D i s u b s t i t u t e d B e n z e n e M o i e t y Abstract: The synthesis of a new family of polyaza-and polyoxapolyazamacrocycles by a simple and efficient one-pot palladiumcatalyzed diamination of 1,3-dibromobenzene is described. The dependence of the nature of the starting polyamines on the yield of the products is demonstrated. The synthesis of N a ,N w -bis(3-bromophenyl)-substituted polyamines is elaborated to obtain intermediates for the synthesis of polyazamacrocycles consisting of two polyamine and two benzene fragments (cyclodimers). The formation of tri-and tetraarylated polyamines is studied and regularities of the process are established. The synthesis of 1,3-bis(polyamino)-substituted benzenes is also described.

Synthesis of Macrocycles Containing Endocyclic Chiral BINAM Moieties

“…At first we compared two approaches for introducing such spacer, the first one employing the reaction of BINAM with N,N'-bis(bromophenyl) substituted oxadiamine, the second one using the coupling of N,N'-bis(bromophenyl) substituted binaphthalene-2,2'-diamine with free oxadiamine. According to the first method, we synthesized N,N'-di(3-bromophenyl) substituted dioxadiamine 2 starting from dioxadiamine 1a according to the known procedure, [17] and then introduced it in the macrocyclization reaction with (S)-BINAM using two catalytic systems: Pd(dba) 2 /BINAP and Pd(dba) 2 /DavePhos (Scheme 1). The reactions were run in boiling dioxane with equimolar amounts of the reagents (c=0.02 M) in the presence of sodium tert-butoxide taken as a base.…”

“…Compound 2 was synthesized according to a procedure described. [17] 7, 14,15,17,18,21,22,12:27, [1,2- [1,4,7,13,18,24]dioxatetraazacyclohexacosine (3a). A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with compound 2 (0.1 mmol, 46 mg), Pd(dba) 2 (8 mol%, 4.5 mg), BINAP (9 mol%, 5.5 mg), absolute dioxane (5 ml), (S)-BINAM (0.1 mmol, 28.5 mg) was then added followed by sodium tert-butoxide (0.3 mmol, 29 mg).…”

“…Obtained from compound 7 (0.13 mmol, 82 mg), dioxadiamine 2b (0.13 mmol, 26 mg), in the presence of Pd(dba) 2 1, 2,8,9,10,11,13,14,16,17,19,20,21,22,28,7:27, [1,4,7,11,18,23, (13). A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with (S)-BI-NAM (2.4 mmol, 674mg), 1,3-dibromo-5-(bromomethyl)benzene (4.8 mmol, 1551 mg), acetonitrile (24 ml) and potassium carbonate (9.6 mmol, 1325 mg).…”

Macrobicycles based on cyclen and cyclam containing 1,3-disubstituted adamantane moiety

“…25 The N,N'-dipyridyl derivative of this amine was synthesized by us earlier 26 and showed nootropic effect in mice. Having acquired a good experience in the synthesis of polyazamacrocycles via Pd-catalyzed amination reactions, [27][28][29][30] we decided to investigate the applicability of this approach to previously unknown adamantane-containing macrobicycles derived from cyclen and cyclam.…”

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

“…[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.…”