Huo et al. BMC Chemistry (2019) 13:89 https://doi.org/10.1186/s13065-019-0606-7 BMC Chemistry REVIEW Open Access A minireview of hydroamination catalysis: alkene and alkyne substrate selective, metal complex design Jingpei Huo*† , Guozhang He, Weilan Chen, Xiaohong Hu, Qianjun Deng and Dongchu Chen*† Abstract Organic compounds that contain nitrogen are very important intermediates in pharmaceutical and chemical industry. Hydroamination is the reaction that can form C–N bond with high atom economy. The research progress in metals catalyzed hydroamination of alkenes and alkynes from the perspective of reaction mechanism is categorized and summarized. Keywords: Hydroamination, Atom economy, C–N bond, Metal catalysis Introduction including the substrate classes of saturated fat primary More and more attention are attracted in hydroamina- amine, saturated fatty secondary amine and unsaturated tion reaction as a tool for N–H synthesis, plenty of com- fatty amine, but extended to structurally related com- plementary synthetic methods have come to the fore for pounds with selective, reactivity and productive yield. the development of intensifed and industrially relevant Moreover, intra- and inter-molecular hydroamination C–N forming processes [1, 2]. According to our statis- reactions will be mentioned as well if they are necessary tics, synthesizing C–N via hydroamination reaction has for the discussion or might act as springboard for future become a promising area of research, experiencing grow- research. ing diversifcation [3, 4]. Since the frst publications on this hydroamination reaction over past years, close to 450 The efects of diferent compounds containing N–H research papers have been published on this topic [5, 6]. Saturated fatty primary amine Further statistics indicate 78% of the published research Fatty primary amines (C1 to C12) are essential intermedi- can be classifed as substrates which work under mild ates for the chemical and pharmaceutical industries. A conditions as follows [7, 8]. At the same time, with the large amount of fatty primary amine and the correspond- development of hydroamination, various catalytic sys- ing derivatives are according to their cationic surface tems have been gradually systematized, and many break- activity. through progresses have been made [9, 10]. In 2007, Barry et al [11] introduce organolithium into Te attractive and challenging methods for the forma- the hydroamination reaction between the molecules of tion of C–N bonds are hydroamination reactions. In this cinnamyl alcohol and primary amine 1 (Scheme 1). In review, we will mostly focus on recent developments in the presence of metallic lithium, the nonterminal olefn the efects of diferent substrates containing N–H. In the and primary amine compounds were acquired, such as meantime, usage of the term hydroamidation is not only methylamine, benzyl amine butyl amine, but the yield is only about 50%. On the one hand, it can undergo a favorable proton transfer process to give the more sta- *Correspondence: [email protected]; [email protected] ble amido-alkoxide, thus shifting the equilibrium in the † Jingpei Huo and Dongchu Chen contributed equally to this work desired sense. It is found that they do not introduce Institute of Electrochemical Corrosion, College of Materials Science and Energy Engineering, Foshan University, Foshan 528000, People’s carbonyl and halogenated compounds to saturated fats. Republic of China © The Author(s) 2019. 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BMC Chemistry (2019) 13:89 Page 2 of 12 BuLi(2 equiv) H o (1,3-(SiMe3)2C9H5)Ln(CH2SiMe3)2 N THF, -78 C NH2 Ph OH + MeNH Ph OH 2 C6D6, THF, 3.5 h reflux 1-4 h NHMe 3 1 Yield: 98% Scheme 1 Addition of primary amines to cinnamyl alcohol Scheme 4 Hydroamination of 2,2-dimethylpent-4-enylamine catalyzed by (1,3-(SiMe3)2C9H5)Sc(CH2SiMe3)2(THF) NH2 [Rh(CH CN) COD]BF Ph 3 2 4 Ph NH In 2010, Xu group [13] frstly take advantage of t o Ph ligand, BuOH, 70 C,2 h Ph Ln(CH2SiMe3)3(THF)2 and Indenyl with half-Sandwich 5 2 Yield: 80% η ligands, separating the catalyst and determine its structure via crystal difraction. Te experiment demon- ligand: O strates that the catalyst is very efective for the intramo- P(NEt2)2 P(NEt2)2 lecular hydroamination synthesis of nitrogen heterocyclic Scheme 2 Rh-catalyzed hydroamination of primary aminoalkenes compounds. As for the C6D6 solvent, the intramolecular hydroamination reaction was found in saturated fatty pri- mary amine substrate 3 (Scheme 4). Consequently, these ligands containing yttrium and dysprosium, are highly active in a series of saturated fatty primary amine sub- strates, and are relatively easy to form nitrogen heterocy- clic compounds (yielding 98%). 2005, Collin et al [14] reported the lanthanide com- pounds catalyst intramolecular asymmetric hydroami- nation reaction of saturated fatty primary amine 4 (Scheme 5), which has undergone the activation of iso- propyl group, and further obtained spiral pyrrolidine. Te selectivity of the reaction is good, and the e.e. value reaches 70%. While Collin group [15] designed a kind of highly Scheme 3 The forming Rh complex intermediate state of active lanthanide to catalyze intramolecular asymmet- hydroamination reaction ric hydroamination reaction of saturated fatty primary amine 5 (Scheme 6), introducing the tertiary butyl group into the catalyst, it can get high yield of secondary amine Besides, the reaction conditions are very hard, and the derivatives, the maximum yield can reach 94%, and it has reaction temperature needs to drop to − 78 °C. the very good stereoselectivity, the e.e. value reaches 40%. [Rh(CH3CN)2COD]BF4 possesses a great deal of In 2003, Kim et al [16] formed a bident ligand through benefts, including high activity and efective. In 2010, lanthanide and triphenylphosphine, which catalyzed Julian et al [12] use this compound to catalyze the intramolecular hydroamination reaction of saturated intramolecular hydroamination reaction (Scheme 2). fatty primary amine 6 (Scheme 7), and synthesized a Te catalyst has strong applicability, and it can achieve variety of secondary amines. But the selectivity of this very high catalytic efect, whether it has chlorine atom reaction is not so good, vice product was generated. In (Cl), ester base (COO), ketone (CO), nitrile (CN), or addition, the study found that compared with the cova- hydroxyl (OH) without protection. Meanwhile, this lent radius of neodymium and yttrium, the covalent rhodium ligand is undefned from the ligand, which is radius of dysprosium is small. Terefore, when it cata- formed by the late transition metal such as palladium lyzes intramolecular hydroamination reaction, it can (Pd), platinum (Pt), iridium (Ir), after the rhodium make the product do not change the confguration in a ligand and the carbon-carbon double bond on the bot- short time, and further raise the antipodal selectivity. tom of primary amine substrate 2 formed complexes, In 2008, aiming to synthesizing a novel kind of ligand, it will not reverse, as a result of competitive catalyst Tamm group [17] select rare earth metals and alkali decomposition, forming a non-cyclic precursor, and metal as the hydroamination reaction catalyst, limit- greatly improving the efciency of molecular hydro- ing the geometry of that catalyst. And then its structure gen amination. Besides, the forming Rh complex of was determined by single crystal difraction. Maybe hydroamination reaction was given in the Scheme 3. due to the catalyst is meso-structure, consist of two Huo et al. BMC Chemistry (2019) 13:89 Page 3 of 12 antiseptic, antifungal and other aspects [20]. Terefore, H N the reaction of hydroamination has been one of the hot- NH2 cat.* spots in the research of organic synthesis [21]. In order C6D6, RT Yield: 67% to further enrich the kinds of nitrogenous compounds, 4 ee: 70% chemists synthesized a variety of multifunctional nitro- gen compounds [22]. Based on saturated fatty secondary amine, it will show more complex molecular structure as N N well, meeting the needs of pharmaceutical industry [23]. cat.*: Ln [Li(thf) ] N N 4 In 2010, Randive et al [24] found that it is good for the intermolecular hydroamination reaction in water phase. As for propiolic acid ethyl ester and saturated fat second- Scheme 5 Hydroamination/cyclization of 1-(aminomethyl)-1-allylcyc ary amine 8 (Scheme 9), including dimethylamine, diiso- lohexane by Li2[(R)-C20H12N2-(C10H22)] propyl amine and piperidine, sequentially beta amino ester compounds were acquired. Tis reaction not only H has high regio-selectivity and stereo-selectivity, using N NH2 cat. * the green and inexpensive solvent, providing a pioneer- Yield: 91% ing research method for studying the hydroamination C6D6, RT, 1 h 5 ee: 41% reaction. t In 2010, Toups and Widenhoefer [25] co-found a new CH2Bu t intramolecular palladium catalyzed hydroamination CH2Bu cat.: reaction with substrate 9 (Scheme 10) and divinyl. It is N N involved that this reaction is initiated by the oxidation Ln [Li(thf) ] N N 4 reaction between allyl group of propadiene and the silver 2 t trifuoromethane. palladium ion (Pd +) attack from the CH2Bu t back of the propadiene, forming the π propadiene ligand CH Bu 2 of cationic palladium, and generating the trans product Scheme 6 Hydroamination-cyclization of 1-(aminomethyl)-1-allylcyc at last, and the corresponding reaction mechanism was lohexane by {Li(THF) }{Ln[(R)-C H N (C H )] } 4 20 12 2 10 22 2 displayed (Scheme 11).