Synthesis of Macropolycycles Comprising Diazacrown and Adamantane Moieties via Pd -Catalyzed Amination Reaction

Abstract

N,N'-bis(bromobenzyl) substituted diazacrown ethers were obtained in the reactions of corresponding free diazacrowns with two equivalents of bromobenzyl bromides in high yields. These compounds were introduced in the Pdcatalyzed amination reaction with 1,3-bis(aminomethyl) and 1,3-bis(2-aminoethyl)adamantanes to give macrobicyclic products. The yields were shown to be dependent on the nature of starting diazacrown derivatives and diamines. N,N'-bis(3-bromobenzyl)

Pd-Catalyzed Amination in the Synthesis of a New Family of Macropolycyclic Compounds Comprising Diazacrown Ether Moieties

“…While the use of triamine 10d, oxadiamine 10i,k provided average 25%-35% yields of the macrocyclization products 17d,i,k (entries 16,19,20), the reaction with dioxadiamine 10h resulted in 57% yield of the target cryptand 17h (entry 18), what is the best result ever observed among yields in the Pd-catalyzed macrocyclization reactions. On the other hand, macrotricyclic dimers 21 were isolated in certain cases in much lower yields.…”

“…Yield 47 mg (36%) of a yellow glassy compound. 29,57,60,65,8,12,16,23,32,39,43,47,32 .1 3,7 .1 17,21 .1 34,38 . 1 48,52 ]-hexaheptaconta-3(76), 4,6,17(75), 18,20,34(69) 3,7 .1 19,23 ]tetraconta-3(40), 4,6,19(39) 3,7 .1 20,24 ]hentetraconta-3(41), 4,6,20(40), 21,23-hexaene (15f).…”

“…Yield 27 mg (20%) of a yellowish glassy compound. 13,26,29,42,45,58,61,66,7,16,23,32,39,48,32 .2 3,6 . 1 17,21 .1 34,38 .1 49,53 ]-ocatheptaconta -3,5,17(76), 18,20,34(70), 35,37,49(69), 50,52,77-dodecaene (19h).…”

“…Yield 14 mg (10%) of a yellowish glassy compound. ,16,29,32,8,19,.1 3,7 .1 20,24 ]hentetraconta-3(41), 4,6,20 (40),21,23-hexaene (15i). Obtained from compound 6 (0.25 mmol, 139 mg), dioxadiamine 10i (0.25 mmol, 51 mg) in the presence of Pd(dba) 2 (12 mg, 8 mol%), BINAP (14 mg, 9 mol%), NaOt-Bu (0.75 mmol, 72 mg) in abs.…”

“…Our interest in this field arises from the possibilities of the application of the catalytic Buchwald-Hartwig amination in the construction of the polymacrocyclic systems capable of selective metal cations coordination. We have already successfully used this approach for the synthesis of macrobicycles comprising tetraazamacrocyclic [12][13][14] moieties and made the first steps in the formation of polymacrocyclic structures based on aza-and diazacrown ethers [15,16].…”