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

Abstract

We report a method for the catalytic, enantioselective intermolecular addition of aliphatic amines to acyclic 1,3-dienes. In most cases, reactions proceed efficiently at or below room temperature in the presence of 5 mol % of a Pd catalyst bearing a PHOX ligand, generating allylic amines in up to 97:3 er. The presence of an electron-deficient phosphine within the ligand not only leads to a more active catalyst but also is critical for achieving high site selectivity in the transformation.

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

“…Finally, based on precedent studies (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) and the above-mentioned findings (see Supplemental Information for more results), a mechanistic profile is proposed for this transformation. As illustrated in Scheme 2, the reaction is initiated by a Ni(0) species ( I ), which undergoes oxidative addition to form a Ni(II)-H species ( II ).…”

“…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...…”

“…As an extension of our studies with nickel-catalyzed carbon-carbon bond formations (Li et al., 2019b, Wang et al., 2019), we turned our attention to carbon-heteroatom bonds. Inspired by the recent reports on metal/Brønsted acid dual catalysis (Adamson et al., 2017, Dion and Beauchemin, 2011, Han et al., 2018, Kathe and Fleischer, 2019, Lin et al., 2019, Liu and Feng, 2018, Löber et al., 2001, Park and Malcolmson, 2018, Yang and Dong, 2017, Zhou and Hartwig, 2008), we have developed a novel, room temperature nickel/Brønsted acid-catalyzed asymmetric hydroamination using conjugated dienes as a limiting reagent (Figure 1D). This protocol can transform a wide array of primary and secondary amines into allylic amines in high yields with excellent enantioselectivities.…”

Catalytic Hydrothiolation: Regio- and Enantioselective Coupling of Thiols and Dienes

“…The regiocontrol observed supports a mechanism distinct from what was previously proposed for related hydroaminations. 5h10a Further studies are warranted to elucidate the mechanism and develop access to other re-gioisomers.…”