Transition Metal-Free Generation of N‑Unsubstituted Imines from Benzyl Azides: Synthesis of N‑Unsubstituted Homoallylic Amines Suman Pramanik, Reddy Rajasekhar Reddy, and Prasanta Ghorai* Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Indore By-pass Road, Bhauri, Bhopal 462066, India * S Supporting Information ABSTRACT: An efficient transition metal-free approach for the generation of N-unsubstituted imines from azides followed by trapping with allyl nucleophile to provide N-unsubstituted homoallylic amines has been described. Although catalytic KO t Bu in DMSO is sufficient to allow imine generation, stoichiometric KO t Bu is essential in THF. Further, an enantio- and diastereoselective synthesis of homoallylic amines from benzyl azide has also been exemplified. I mines are important intermediates for the synthesis of amines, 1 N-containing natural products, 2 and other trans- formations. 3 In general, imines are unstable in nature, and their synthesis and isolation have remained a continuing challenge in organic chemistry. The synthetic methods available in the literature are mostly for the synthesis of N-substituted imines. 4 These methods are mostly based on the condensation of carbonyls with an amine counterpart where the equilibrium favors imine with N-substitution. Nevertheless, acquiring an N- unprotected amine through an N-protected imine always requires an additional step for the removal of the corresponding N-protection. 5,6a Therefore, the reactions through the N- unsubstituted imines would be highly important, leading to the shorter, atom-economical, and waste-free routes (Scheme 1). In this context, an aminoallylation of aldehydes using ammonia has been developed by Kobayashi et al.; 5a never- theless, the imine intermediate has not been isolated or characterized. Further, excess ammonia is needed because of the reversibility of the reaction that limits the range of different nucleophiles that can be used for this method. Further, N- metalloketamines from alkyl nitrile have been developed and used for hydrogenation 5b and allylation. 5c In the past decade, many methods based on transition metal-imine complexes involving the transition metal or noble metals have been developed. 6 Recently, Rhee, Park, and co-workers 6a reported a Ru-catalyzed synthesis of imines from azides and further utility for the synthesis of homoallylic amines. Synthesis of azaspirocyclohexadienes from α-azido-N-arylamides through the generation of N-unsubstituted imines has been reported by Chiba et al. using Cu catalyst. 6b However, identification of transition metal-free methods is important to avoid metallic impurities in products. 7 Encouraged by the recent progress in the efficient synthesis of azides, 8 we became interested in developing a supplemental transition metal-free strategy for the synthesis of N-unsubstituted imines from alkyl azides. Further, the trapping of in situ-formed N-unsubstituted imines would provide the corresponding N-unsubstituted amines. Here, we developed a base-promoted decomposition of α-H-containing azides to generate imine followed by trapping with allylpinacol borane to provide the speculated homoallylic amines (see Scheme 2). We started the initial screening for the conversion of benzyl azides to the corresponding homoallylic amines 9 using various bases such as Et 3 N, ethylenediamine (en), TMEDA, pyridine, NaH, NaOMe, NaOEt, NaO t Bu, and KO t Bu in THF using allylpinacol borane as the allylating reagent. Interestingly, only KO t Bu was found to be effective in providing homoallylic amine 3a (Table 1, entries 1-9), whereas other bases failed to initiate the formation of imine itself. NaO t Bu did not even react with azide 1a, probably because of its weaker basicity compared to that of KO t Bu. Among several solvents, only THF, DMSO, Received: December 10, 2014 Scheme 1. Synthesis of N-Unsubstituted Amine from Azides Scheme 2. Synthesis of Homoallylic Amines from Azides Promoted by Base Note pubs.acs.org/joc © XXXX American Chemical Society A DOI: 10.1021/jo502794q J. Org. Chem. XXXX, XXX, XXX-XXX