Asymmetric catalysis for enantioselective intramolecular hydroamination of alkenes is a critical method in the construction of enantioenriched nitrogen-containing rings, often prevalent in biologically active compounds and natural products. Herein, we demonstrate a facile enantioselective intramolecular hydroamination of alkenes for the synthesis of chiral pyrrolidine, piperidine, and indoline moieties, using a manganese (II) chiral aprotic cyclic urea catalyst. The cyclic ligand hinders the inversion of the N atom of the urea and effectively discriminate between the enantiomers of substrates. High-resolution mass spectrometry, deuterium labeling experiments, and molecular orbital energy analysis clearly reveal the intermediates and mechanism of the transformation. As a key step, oxygen coordination by chiral aprotic urea presents a robust control over the asymmetric intra-HA reaction through the involvement of a convergent assembly of two vital intermediates (Mn-N and C-Mn-Br), providing access to chiral cyclic amine systems in high yields with excellent enantioselectivity. Nitrogen-containing rings containing chiral carbon centers are a staple of bioactive molecules and natural products of interest, and synthetic methodologies for their development are a continual focus of organic chemists. Here, the authors disclose a protocol for the synthesis of enantioenriched saturated azacycles, via intramolecular hydroamination of alkenes, using a chiral cyclic urea ligand with manganese.

Due to the robust electrophilic properties of the trifluoromethyl group (-CF3), its incorporation into organic compounds can markedly alter their ester affinity, stability, bioavailability, and other properties. The trifluoromethylation reaction is currently experiencing rapid advancement, with an expanding array of substrates and the emergence of novel methodologies. Consequently, compounds containing the -CF3 moiety find extensive utility across diverse fields. This article aims to comprehensively review the latest advancements in trifluoromethylation reaction of olefins, aldehydes, and ketones, encompassing nucleophilic trifluoromethylation, electrophilic trifluoromethylation, and radical trifluoromethylation. The discussion includes an exploration of the types and broadening scope of applicable substrates. Furthermore, this article addresses the associated challenges and delineates prospective directions for future developments in trifluoromethyl reaction.

Asymmetric catalysis with a chiral (Salen)Mn(III) complex is applied successfully to highly enantioselective intramolecular haloamination reactions of alkenes through a chiral aziridinium ion ring-opening sequence. Computational and experimental studies suggested that the C5-C6 bond polarization has a major effect on the regioselectivity of the chiral aziridines ring intermediate, and steric hindrance of groups at C5 or C6 plays a minor role. Various amino-alkenes can cyclize under the reaction conditions to obtain 2-brominated/chlorinated pyrrolidine and indoline derivatives with excellent yield and enantioselectivity.

A free-radical halotrifluoromethylation of olefins by using Mn(OAc)3·2H2O, CF3SO2Na, and perhalogenated carboxylic acids has been achieved. Perhalogenated carboxylic acids act as a halogen source and CF3SO2Na acts as a CF3 source. The reaction displayed good tolerance of functional groups in the substrates under mild conditions. The radical clock experiment and TEMPO inhibition experiment support a radical process. The halogen reagent competition experiment shows that the last step of halogenation process is mainly through a halogen abstraction mechanism.

A simple and efficient method for hydrotrifluoromethylation of unactivated alkenes was reported. The reaction relied on the single electron oxidation of a commercially available sodium trifluoromethanesulfinate (CF3SO2Na, Langlois' reagent) using Mn(OAc)3·2H2O as the oxidant and the subsequent addition of trifluoromethyl radical to C═C double bonds. The reaction proceeded readily under mild conditions with good tolerance of a variety of functional groups in the substrates. The preliminary reaction mechanism was studied with deuteration, radical clock, and TEMPO inhibition experiments.

The preparation of prolinol ether type compounds was realized via MnI2-catalyzed intramolecular iodoamination of unfunctionalized olefins and subsequent ring opening of an aziridinium ion intermediate with alcohols/phenols. In the presence of a catalytic amount of MnI2 and 2 equiv of NaI, intramolecular aminoalkoxylation of different N-benzyl-5-methylhex-4-en-1-amine substrates proceeded readily in alcoholic solvents, leading to 2-(alkoxyalkyl)pyrrolidine products in up to 90% isolated yields.

Using (trifluoromethyl)trimethylsilane (TMSCF3 ) as the trifluoromethylating agent, MgCl2-catalyzed trifluoromethylation of carbonyl compounds proceeded readily at room temperature. In the presence of 10 mol% of MgCl2, a variety of carbonyl substrates such as aliphatic/aromatic aldehydes, acyclic/cydic ketones and esters could be trifluoromethylated in DMF, giving the corresponding trimethylsilyl ethers (ketals) in up to 93% isolated yields. Trifluoromethylketones could be readily obtained after hydrolysis of the trimethylsilyl ketals. The reactions could tolerate air and moisture, and the use of oxygen and moisture-free conditions was not required. (C) 2017 Published by Elsevier Ltd.

MnI2-catalyzed intramolecular iodoamination of unfunctionalized olefins was reported. Interaction of MnI2 with N-alkenyl amine/sulfonamide gave NRMnI which produced a CH2MnI intermediate via intramolecular aminometallation of CC double bond. Reductive elimination of CH2I from CH2MnI produced iodomethyl heterocycle with the release of Mn(0) which was confirmed by XPS and XRD experiments.

A general and practical method for the preparation of trans-2-substituted-4-halopiperidines and cis-2-substituted-4-halotetrahydropyrans is reported. Using 5 mol % of AlCl3 as the catalyst and 2 equiv of trimethylsilyl halides as the halide sources, aza-Prins cyclization of N-tosyl homoallylamine or Prins cyclization of homoallylic alcohol with carbonyl compounds could be readily realized, giving the corresponding trans-2-substituted-4-halopiperidines or cis-2-substituted-4-halotetrahydropyrans in high yields and satisfactory diastereoselectivity.

Whereas the title reaction between N-tosyl homoallylamine with aryl or alkyl aldehydes and trimethylsilyl bromide, chloride or iodide delivers the corresponding 2-substituted 4-halopiperidines with high trans selectivity, application of trimethylsilyl fluoride provides mixtures of cis and trans isomers.

Trifluoroacetic acid was found to be effective in intramolecular hydroamination of unfunctionalized olefins bearing electron-rich amino groups, and the corresponding N-heterocycles were obtained in good isolated yields. The scope of the substrates was investigated, and a possible reaction mechanism was proposed. Substituents on CC double bonds and amino groups of the substrates showed drastic effects on the course of the reactions.

The catalytic activity of benzoic acid could be increased by introducing a hydrogen bond donor group at the ortho-position. Preliminary OFT calculation indicated that the activation of C=C double bond was realized by the action of both the carboxyl group and the hydrogen bond donor. The amino group was brought to the activated C=C bond by the interaction between the carboxyl oxygen and amino proton. This interaction also increased the nucleophilicity of the amino group. Thus, in the presence of 20 mol % of 2-(trifluoromethanesulfonamido)benzoic acid, intramolecular hydroamination of unfunctionalized olefins gave the corresponding products in up to 95% isolated yields. (C) 2015 Elsevier Ltd. All rights reserved.

ChemInformVolume 46, Issue 52 Preparative Organic Chemistry ChemInform Abstract: The Effect of Hydrogen Bond on Broensted Acid-Catalyzed Intramolecular Hydroamination of Unfunctionalized Olefins. Ting-Ting Li, Ting-Ting Li Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorGong-Qing Liu, Gong-Qing Liu Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorYu-Mei Wang, Yu-Mei Wang Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorBin Cui, Bin Cui Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorHui Sun, Hui Sun Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorYue-Ming Li, Yue-Ming Li Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this author Ting-Ting Li, Ting-Ting Li Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorGong-Qing Liu, Gong-Qing Liu Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorYu-Mei Wang, Yu-Mei Wang Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorBin Cui, Bin Cui Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorHui Sun, Hui Sun Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this authorYue-Ming Li, Yue-Ming Li Coll. Pharm., Nankai Univ., Tianjin 300071, Peop. Rep. ChinaSearch for more papers by this author First published: 10 December 2015 https://doi.org/10.1002/chin.201552026Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue52December, 2015 RelatedInformation