Rhodium-Catalyzed Hydrofunctionalization: Enantioselective Coupling of Indolines and 1,3-Dienes

Abstract

We communicate a strategy for the hydrofunctionalization of 1,3-dienes via Rh-hydride catalysis. Conjugated dienes are coupled to nucleophiles to demonstrate the feasibility of novel C-C, C-O, C-S, and C-N bond forming processes. In the presence of a chiral JoSPOphos ligand, hydroamination generates chiral allylic amines with high regio- and enantioselectivity. Tuning both the pK and steric properties of an acid-additive is critical for enantiocontrol.

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

“…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). 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,…”

“…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...…”

Alkyl halides as both hydride and alkyl sources in catalytic regioselective reductive olefin hydroalkylation

“…In this respect, the installation of a hydrogen and carbon-based moiety across πsystems represents an effective strategy for C-C bond construction [4][5][6] . Numerous hydrocarbofunctionalization protocols rely on conjugation (i.e., 1,3-dienes [7][8][9][10][11] , olefins such as styrenes [12][13][14] , alkenyl boronates 15,16 , and Michael acceptors 17 ) to deliver high regioselectivity. In contrast, reactions with unactivated aliphatic C=C bonds are typically plagued by lower substrate reactivity and/or poorer regiochemical differentiation leading to unsatisfactory levels of site selectivity.…”

Enantioselective Intermolecular Addition of Aliphatic Amines to Acyclic Dienes with a Pd–PHOX Catalyst

“…Dong and co-workers demonstrated a Rh-catalyzed 1,2-hydroamination of unsymmetrical acyclic dienes utilizing indoline nucleophiles; in this case, an acid additive positively impacts enantioselectivity. 6 Recently, the Hou lab disclosed the first highly enantioselective intermolecular hydroaminations with aliphatic amines, where chiral lanthanide half-sandwich catalysts allow for stereoselective amine additions to cyclopropenes. 7–10 In this work, we report the enantioselective 1,2-addition of alkyl amines to unsymmetrical acyclic dienes 11–13 catalyzed by a cationic Pd–PHOX complex.…”