Studies concerning the electrophilic amino-alkene cyclisation for the synthesis of bicyclic amines

Abstract

The bromination of a series of cyclohexenyl substituted secondary amines 1a-i has been investigated using Br2, PHT and NBS. In the case of Br2 and NBS the secondary amines preferentially undergo N-bromination. In contrast, PHT cleanly affords the products of alkene dibromination. In the case ofBr2 the N-bromo species then give the products of alkene dibromination, albeit less efficiently. On subsequent treatment with K2CO3 these dibromides form the corresponding hexahydroindoles 2a-h and octahydroquinoline 2i. The presence of an N-substituent bearing a stereogenic centre (1h and 1i) was studied and the products 2h and 2i were isolated with no diastereoselectivity. When NBS was used a novel cyclisation, forming bromo-substituted octahydroindoles 9a,b and d, was observed. In relation to this sequence it was shown that these products were not intermediates in the former Br2/PHT processes and that the reaction only proceeded in the presence of the succinimide by-product of N-bromination.

Halogen Bonding of N‐Halosuccinimides with Amines and Effects of Brønsted Acids in Quinuclidine‐Catalyzed Halocyclizations

“…Next, the reaction of amines with NBS was investigated in CDCl 3 ( Scheme 2 ,A ). Primary benzylamine and secondary N ‐methylbenzylamine were readily oxidized to their N ‐bromo amines and released succinimide even at low temperature, as evidenced by 1 H‐NMR spectroscopy (see Supporting Information for details) [45] . However, when NBS was mixed with equimolar amounts of quinuclidine, the NBS and quinuclidine signals shifted upfield and downfield, respectively.…”

“… [31–42] For instance, according to literature reports, NIS and NBS are one of the most common reagents used to oxidize N−H bonds to N−X bonds [43] . Indeed, it is reported that primary and secondary amines are readily oxidized by NIS to give N ‐iodo amines, [44] while secondary amines are readily oxidized by NBS to generate N ‐bromo amines ( Scheme 1 ,A , equation 1 ) [45] . Also, tertiary amines are reported to react readily with NIS or NBS to form N ‐halo‐ammonium salts ( Scheme 1 ,A , equation 2 ) [47] .…”

An Approach to the Stereoselective Synthesis of Enantiopure Dihydropyrroles and Aziridines from a Common Sulfinyl-Sulfinamide Intermediate

“…Additionally, very few efficient methods for obtaining enantiopure trans -2,5-disubstituted pyrrolidines have been reported . Among the different strategies, one straightforward route to five-membered N -heterocycles is the amino cyclization of chiral γ,δ-unsaturated amines, and substantial research has been devoted to this subject …”

Oxidative Amidation of Nitroalkanes with Amine Nucleophiles using Molecular Oxygen and Iodine

“…[5][6][7] This was the case even by directly reacting pre-formed N-bromo amines (or 15,see above) with the aci-nitronate of 1;i nf act, this generated the a-bromo analogue of 4 in good yields. [16] Having confirmed the aiodide 4 as the primary intermediate,t wo possible pathways to form the amide product 7 were considered;o ne pathway being where an oxygen molecule first reacts with 4 before the amine component, and in the other pathway the amine reacts with 4 first. Thus,t he relative reactivities of the amine and oxygen components were investigated through aset of control experiments (Scheme 4).…”