Microwave-assisted aza-Prins reaction. Part 2: straightforward access to 2,6-disubstituted 1-azaadamantanes

Abstract

Novel symmetrically and unsymmetrically disubstituted 1-azaadamantanes were prepared as a single, chiral diastereomer via double microwave-assisted aza-Prins cyclization in one-pot or sequential reaction format.

Facile construction of the all-bridge-position-functionalized 2,4,6,8-tetraazaadamantane skeleton and conversion of its N-functionalities

“…, daphodhamine B 1 and terengganensine A 2 ), drugs 3 ( e.g. , antiemetics, 4 antivirals, 5 bactericidals, 3 c ,6 analgesics, 7 and anticancer drugs 8 ), energetic materials, 9 organocatalysts, 10 organoligands, 11 organic redox mediators, 12 etc . Considerable progress has also been made in the post-synthesis of azaadamantanes.…”

“…Considerable progress has also been made in the post-synthesis of azaadamantanes. For example, azaadamantanes with multiple substituents including 4-substituted, 3 a ,13 2,4-, 14 2,6-, 4 3,5- 15 disubstituted, and polysubstituted 3 b ,9 c , d ,11 c ,16 1-azaadamantanes, as well as 2-, 17 4- 18 substituted, 2,6-disubstituted, 19 and polysubstituted 9 b ,17 a ,20 2-azaadamantanes have been simply synthesized. Diazaadamantanes such as 2,6-disubstituted 21 and polysubstituted 20 b ,22 2,6-diazaadamantanes, as well as 4-substituted 23 and polysubstituted 6 b , c ,7 b ,23,24 1,3-diazaadamantanes have also been masterly prepared.…”

Synthesis of 2-Azaadamantan-6-one: A Missing Isomer

“…Aza and polyazaadamantanes continue to play important roles in organic and medicinal chemistry. − Among the most useful members of the azaadamantane family are the azaadamantanones 1–4 (Figure ). 1-Azaadamantane-4-one ( 2 ), the first azaadamantanone isomer to be described, was synthesized from amino ketal 5 in a double intramolecular Mannich reaction , (Scheme ) and has figured prominently in diastereofacial selection studies. , More recently, the highly pyramidalized reactive lactam 1-azaadamantan-2-one ( 1 ) was obtained by the pyrolysis of N -Boc amino acid 6 .…”

Synthesis of 4,8,9,10-Tetrafunctionalized 2-Azaadamantanes and Their 2-Azaprotoadamantane Skeleton Isomers

“…These provide a reliable method for the subsequent derivation of multifunctional 2-azaadamantane and its skeleton isomer 2-azaprotoadamantane, which might be used as basic scaffolds for high energy density cage-like compounds. Keywords azaadamantane; azaprotoadamantane; functionalization; ammonolysis; cyclization, nitramine; synthesis design 氮杂金刚烷是一类刚性的、具有多个衍生位点的笼 型有机骨架, 是很多天然产物(例如 Daphodhamine B [1][2] 及 Terengganensine A [3] )、 药物(可以用于止吐 [4] 、 镇痛 [5][6] 、 抗病毒 [7] 、抗菌 [8][9][10] 及抗肿瘤 [11][12] )、含能材料 [13][14] 、有 机催化剂 [15][16][17][18][19][20][21][22] 及有机配体 [23][24][25] 等物质的核心单元, 一直 是有机化学家的研究热点. 氮杂金刚烷衍生物的合成也 取得了相当大的进展.…”