Copper-promoted synthesis of 1,4-benzodiazepinones via alkene diamination

Abstract

A new method for the synthesis of 2-aminomethyl functionalized 1,4-benzodiazepin-5-ones is presented. The benzodiazepine core is well-known to interact with biological receptors and many pharmaceutical drugs are derived from this structure. The alkene diamination strategy is employed for the first time for the synthesis of 1,4-benzodiazepinones. In this reaction, copper(2-ethylhexanoate)2 serves as promoter and a range of external amines can be coupled with 2-sulfonamido-N-allyl benzamides to generate the 1,4-benzodiazepinones in good yields.

Stereoselective and Regioselective Synthesis of Heterocycles via Copper-Catalyzed Additions of Amine Derivatives and Alcohols to Alkenes

“…This reaction provided a differentially protected vicinal diamine. Under similar conditions 7-membered ring 1,4-benzodiazepinones can be formed (Scheme b) . Although we have not yet developed a diamination that can employ electron-rich primary amines, a protocol employing sulfamide substrates can provide electron-rich vicinal diamines upon reduction (Scheme c). , Less reactive substrates undergo diamination more efficiently when organic soluble copper­(II) carboxylates are used in nonpolar solvents.…”

Progress in Difunctionalization of Alkenes

“…随后, 2008 年该课题 组 [7] 又对此反应进行了不对称方面的研究, 筛选出(R)-DTBM-SEGPHOS 为手性配体, 但是只得到了中等的 ee 值(Scheme 1). 2015 年, Chemler 课题组 [14] 又通过烯烃的二氨化反 应合成 2-氨甲基取代的 1,4-苯并二氮杂卓-5-酮类化合 物, 都得到了很好的产率(Scheme 7).…”

Transition‐Metal‐Catalyzed 1,2‐Diaminations of Olefins: Synthetic Methodologies and Mechanistic Studies

“…Transition metal‐catalyzed cascade alkene difunctionalizations‐larger rings are usually more challenging compared to five‐membered ring formation. In 2015, highly effectual and multipurpose Cu(2‐ethylhexanoate) 2 /Cs 2 CO 3 mediated cascade intra‐/intermolecular alkene diamination and cyclization approach have been established first time by Sherry R. Chemler and research group starting from readily accessible N ‐nosyl‐2‐amino‐ N ‐allylbenzamide or analogues 7 , TsNH 2 , Cu(2‐ethyl hexanoate) 2 (as a promoter) and Cs 2 CO 3 to synthesize densely aminomethyl‐functionalized 1,4‐benzodiazepinones 8 a – q in moderate to high yields (40‐79 %) ( Scheme 3 ) [70] . This cyclization/diamination strategy well tolerated with diverse external amines such as benzamide 8 e , tosamide 8 a – c & 8 l – p , trimethylsilylethylsulphon‐amide 8 f , cyclopropylsulphonamide 8 i , 4 trifluoromethyl aniline 8 k , and other appropriate aryl‐sulphonamides 8 g – h , 8 j , 8 q to furnished challenging fused 7‐membered heterocycles in a single synthetic operation and mild conditions.…”