Hydroamination of Alkenes

Abstract

The addition of an amine NH‐functionality to alkenes (including vinyl arenes, conjugated dienes, allenes or ring‐strained alkenes), the so‐called hydroamination, represents a simple and highly atom‐economical approach for the synthesis of nitrogen‐containing products. A large variety of catalyst systems are available, ranging from alkali, alkaline earth, rare earth, Group 4 and Group 5 metals, to late transition metal catalysts, and, less prominent, Brønsted and Lewis acid‐based catalyst systems. The mode of operation of these catalyst systems can vary significantly and the different reaction mechanisms and the scope and limitations are discussed. While intramolecular hydroamination reactions can be readily achieved with a large number of catalyst systems, significantly fewer examples for the more challenging intermolecular hydroamination are known, especially for unactivated alkenes. The stereoselective hydroamination has also received significant attention due to the importance of chiral nitrogen‐containing molecules in pharmaceutical industry. A variety of highly selective chiral catalyst systems have been developed for intramolecular hydroaminations, while examples of intermolecular asymmetric hydroaminations are scarce. Hydroamination in the context of this review article is defined as the addition of HNR 2 across a non‐activated, unsaturated carbon‐carbon multiple bond. This review focuses on the hydroamination reaction of simple, non‐activated alkenes. The addition of amines to slightly activated alkenes, such as vinyl arenes, 1,3‐dienes, strained alkenes (norbornene derivatives, methylenecyclopropenes) and allenes is closely related and is covered as well. However, hydroamination reactions of alkynes and Aza‐Michael reactions involving the addition of an N‐H fragment across the conjugated or otherwise activated double bond of a Michael acceptor are not covered. The scope of amine types includes ammonia, primary and secondary aliphatic and aromatic amines, azoles, and hydrazines. N ‐Protected amines, such as ureas, carboxamides, and sulfonamides are covered as well, as they are important substrates for metal‐free and late transition metal‐based catalysts. The literature through January 2011 will be covered with two selected references from 2012 (comprising Table 3D). A supplemental reference list is provided for reports appearing February 2011 through April 2015. The chapter is organized by the nature of the carbon unsaturation to which the amine is added. Ranging from less reactive substrates such as ethylene and unactivated alkenes, to slightly activated substrates, such as vinyl arenes, and more activated substrates, including conjugated dienes, allenes and strained alkenes. Enantioselective hydroamination reactions, an area that has seen significant progress over the past decade, are discussed next. Finally, tandem hydroamination/carbocyclization reactions of aminodialkenes provide rapid access to complex alkaloidal skeletons. The tables at the end of the chapter are separated into five main sections: achiral intermolecular hydroamination, achiral intramolecular hydroamination, enantioselective intermolecular hydroamination, enantioselective intramolecular hydroamination, and tandem hydroamination/carbocyclization. Within the first four sections the tables are further divided into subsections based on the participating alkene, i.e. alkenes, vinyl arenes, dienes, allenes, and strained alkenes.

Nickel/Brønsted Acid-Catalyzed Chemo- and Enantioselective Intermolecular Hydroamination of Conjugated Dienes

“…Therefore, organic chemists have made considerable efforts toward their synthesis during the last decade (Grogan, 2018, Li and Zhang, 2014, Nugent and El-Shazly, 2010, Patil et al., 2018, Robak et al., 2010). Among them, asymmetric hydroamination of unsaturated C-C bonds serves as an efficient and powerful tool in organic synthesis, particularly hydroamination using free amines (Aillaud et al., 2007, Clement and Jerome, 2017, Dondoni, 2015, Hannedouche and Schulz, 2013, Hannedouche and Schulz, 2018, Hii, 2006, Huang et al., 2015, Huo et al., 2019, Jerome, 2018, Müller et al., 2008, Patel et al., 2017, Pirnot et al., 2016, Reznichenko and Hultzsch, 2016, Zi, 2009, Zi, 2011). In this context, transition-metal-catalyzed intermolecular asymmetric hydroamination of allenes (Berthold and Breit, 2018, Berthold et al., 2019, Cooke et al., 2012, Dion and Beauchemin, 2011, Lin et al., 2019, Parveen et al., 2017, Xu et al., 2016), alkynes (Athira et al., 2018, Liu et al., 2011, Lutete et al., 2004, Patil et al., 2006, Xu et al., 2019), and conjugated dienes (Adamson et al., 2017, Dion and Beauchemin, 2011, Lin et al., 2019, Löber et al., 2001, Park and Malcolmson, 2018, Xiong et al., 2018, Yang and Dong, 2017, Zhou and Hartwig, 2008) has been extensively studied (Figure 1B).…”

“…In this context, transition-metal-catalyzed intermolecular asymmetric hydroamination of allenes (Berthold and Breit, 2018, Berthold et al., 2019, Cooke et al., 2012, Dion and Beauchemin, 2011, Lin et al., 2019, Parveen et al., 2017, Xu et al., 2016), alkynes (Athira et al., 2018, Liu et al., 2011, Lutete et al., 2004, Patil et al., 2006, Xu et al., 2019), and conjugated dienes (Adamson et al., 2017, Dion and Beauchemin, 2011, Lin et al., 2019, Löber et al., 2001, Park and Malcolmson, 2018, Xiong et al., 2018, Yang and Dong, 2017, Zhou and Hartwig, 2008) has been extensively studied (Figure 1B). Nevertheless, the use of noble transition metals such as rhodium and palladium are often mandatory (Adamson et al., 2017, Aillaud et al., 2007, Athira et al., 2018, Berthold et al., 2019, Berthold and Breit, 2018, Clement and Jerome, 2017, Cooke et al., 2012, Dion and Beauchemin, 2011, Dondoni, 2015, Hannedouche and Schulz, 2013, Hannedouche and Schulz, 2018, Hii, 2006, Huang et al., 2015, Huo et al., 2019, Jerome, 2018, Lin et al., 2019, Liu et al., 2011, Löber et al., 2001, Lutete et al., 2004, Müller et al., 2008, Park and Malcolmson, 2018, Parveen et al., 2017, Patel et al., 2017, Patil et al., 2006, Pirnot et al., 2016, Reznichenko and Hultzsch, 2016, Xiong et al., 2018, Xu et al., 2016, Xu et al., 2019, Yang and Dong, 2017, Zhou and Hartwig, 2008, Zi, 2009, Zi, 2011); in addition, these methods suffer from limited amine scope (Adamson et al., 2017, Dion and Beauchemin, 2011, Lin et al., 2019, Löber et al., 2001, Park and Malcolmson, 2018, Xiong et al., 2018, Yang and Dong, 2017, Zhou and Hartwig, 2008), as well as excessive quantities of the unsaturated substrat...…”

Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes

“…Metal-catalyzed hydrofunctionalization of readily available alkenes with nitrogen sources is one of the most efficient methods for the synthesis of nitrogen-containing molecules; however, to achieve the high regio-and enantioselectivities of this transformation is still a challenge ( Fig. 2a) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . Among several activation strategies for alkene hydroamination, metal-catalyzed hydrogen atom transfer (HAT) reaction exhibits great Markovnikov selectivity and chemoselectivity (Fig.…”

Electrochemistry and Photoredox Catalysis: A Comparative Evaluation in Organic Synthesis

“…Olefin hydroamination is a very attractive method for C-N bond formation. For this reason, much effort has been put into designing novel synthetic methods for this transformation [108,109,110,111,112,113,114,115,116]. Possibly the most desirable route is the utilization of nitrogen-centered radicals, which are versatile intermediates for the construction of nitrogen-carbon bonds.…”