One‐Pot Three‐Component Synthesis of Vicinal Diamines via In Situ Aminal Formation and Carboamination

Abstract

A synthesis of vicinal diamines via in situ aminal formation and carboamination of allyl amines is reported. Employing highly electron-poor trifluoromethyl aldimines in their stable hemiaminal form was key to enable both a fast and complete aminal formation as well as the palladium-catalyzed carboamination step. The conditions developed allow the introduction of a wide variety of alkynyl, vinyl, aryl, and hetereoaryl groups with complete regioselectivity and high diastereoselectivity. The reaction exhibits a high functional-group tolerance. Importantly, either nitrogen atom of the imidazolidine products can be selectively deprotected, while removal of the aminal tether can be achieved in a single step under mild conditions to reveal the free diamine. We expect that this work will promote the further use of mixed aminal tethers in organic synthesis.

Recent Developments in Pd0‐Catalyzed Alkene‐Carboheterofunctionalization Reactions

“…Garad and Mhasker ecently reported aP d II -catalyzed CÀHfunctionalization/alkene carboamination procedure for the synthesis of 8-oxoprotoberberine core 20 (Scheme 6). [13] The acylated 2-vinylphenethylamine substrates (19)w ere obtained in three steps (peptide coupling, iodination, and Stille coupling) from the corresponding phenethylamine and ab enzoica cid derivative. Treatment of compound 19 with ac atalytic amount of Pd(OAc) 2 in the presence of one equivalent of Cu(OAc) 2 afforded the heterocyclic products in 35-55 %y ields.…”

“…Orcel and Waser also recently extended this strategy to the synthesis of vicinal diamines, [19] which are important building blocks in the synthesis of complex molecules and as chiral ligands.A ss hown in Scheme 12, the treatment of allylic amines 35 with O-acetyltrifluoroethylamine derivatives 36 and an aryl or alkynylh alide in the presence of ap alladiumc atalyst afforded imidazolidined erivatives 37 via an aminal intermediate. The scope of this method was quite broad, because the reactions could be conducted withavariety of electrophiles,a nd substitution at the allylic positiono rt he internal alkene carbon atom of the substrate (35)w as well-tolerated.…”

Palladium‐Catalyzed Carboxy‐Alkynylation of Propargylic Amines Using Carbonate Salts as Carbon Dioxide Source

“…A higher temperature of 75 °C (entry 4) and a lower temperature of 50 °C (entry 5) both led to a lower yield of 64 %, with the latter giving incomplete conversion. The choice of ligand played a central role in the oxyalkynylation reaction using hemiacetal tether 3 , . Therefore, we examined again the most successful ligands from the previous protocol (DCEPhos, XantPhos and dppf).…”

Transition‐Metal‐Catalyzed Three‐Component Difunctionalizations of Alkenes

“…Several common drug molecules and bioactive compounds (e.g., Rolipram, Baclofin, Phenibut) were prepared by the reaction, which shows the potential synthetic value in organic synthesis. Aminocarbonylation, carboamination, azidocarbonylation, oxycarbonylation, and carbooxygenation of simple alkenes were also achieved to prepare the corresponding functional molecules through palladium catalysis.…”