Palladium‐Catalyzed Intermolecular Asymmetric Hydroamination with 4,4′‐Disubstituted BINAP and SEGPHOS

Abstract

BINAP or SEGPHOS, was synthesized and used for the asymmetric intermolecular hydroamination of aniline to vinylarenes with ee values of up to 85 %, and it is believed that the bulky groups on the 4,4'-positions and the narrower dihedral angle of the biaryl moiety are responsible for the ee enhancement in these reactions.Keywords: asymmetric catalysis; chiral amine; hydroamination; palladium; phosphine Asymmetric hydroamination of olefins is one of the simplest and the most atom-economical methods for the synthesis of chiral secondary amines.[1] The development of efficient asymmetric hydroamination reactions is, however, slow due to the high energy barrier of the C À N bond-forming process. Whereas Marks et al. and others carried out intramolecular asymmetric hydroamination using chiral organolanthanide catalysts, [2] Hartwig et al. and others recently reported a novel Pd-catalyzed intermolecular hydroamination of anilines to vinylarenes to afford Markovnikov addition products.[3] Asymmetric hydroamination has been explored for a few substrates, but only moderate enantioselectivities were obtained.[3a,c] Since we have recently observed significant ee enhancements of 4,4'-disubstituted BINAPs over the parent BINAP in a variety of Ru-catalyzed hydrogenation [4] and Pd-catalyzed C À C bond-forming reactions, [5] we have decided to explore the use of modified BINAPs in Pd-catalyzed asymmetric intermolecular hydroamination reactions. It is also well established that the dihedral angle of the biaryl moiety in chiral chelating phosphines can have significant effects in transition metalcatalyzed asymmetric reactions.[6] SEGPHOS (2; Figure 1), [7] which is believed to have the narrowest dihedral angle among these bisphosphines, indeed gives better ees than others in many Ru-, [7,8] Rh-, [9] Pd-, [10] and Cu-catalyzed [11] reactions. We hypothesize that more enantioselective catalysts for intermolecular hydroamination reactions can be designed by combining the potential positive effects of bulky substituents and narrow dihedral angles in biaryl-based bisphosphines. We decided to combine the 4,4'-substituent effect with the smaller dihedral angle in a SEG-PHOS system. Herein, we report the synthesis and optical resolution of new 4,4'-disubstituted SEG-PHOS (t-Bu-SEGPHOS, 2b) and the applications of 4,4'-disubstituted BINAPs 1 and SEGPHOS 2 in Pd-

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…This initial report focused on the strained alkene norbornene and the less nucleophilic arylamines as substrates. In the early 2000s, Hartwig [117,131] phosphine ligand is critical to promote enhanced reactivity [289]. To this end, the family of Segphos ligands [290] has found preferred application for intermolecular hydroamination with Ir and Pd.…”

Enantio- and Regioselective CuH-Catalyzed Hydroamination of Alkenes

“…1 Although great progress has been made in the field of late transition metal-catalyzed hydroamination, 2 several challenges still exist. For example, the intermolecular process requires activated alkenes such as vinyl arenes.…”

“…For example, the intermolecular process requires activated alkenes such as vinyl arenes. 2a,i,h or acrylic acid derivatives, 2c while asymmetric variants are limited to the addition of aryl amines to simple β -unsubstituted styrene derivatives and achieve only moderate levels of enantiomeric excess. 2a,3 In addition, there are limited methods available to obtain the anti-Markovnikov product in hydroamination reactions of aliphatic amines.…”

Effects of Silyl Substituents on the Palladium‐Catalyzed Asymmetric Synthesis of Axially Chiral (Allenylmethyl)silanes and Their SE2′ Chirality Transfer Reactions

“…The reaction of 1a with 2m with the use of the Pd/(R)-segphos species afforded (R)-3am in 75 % yield with 79 % ee (Table 2, Entry 1). The use of (R)-binap and (R)-tBu-segphos [17] decreased the enantioselectivity of the same reaction to 43 and 74 % ee, respectively (Table 2, Entries 2 and 3). Interestingly, a clear correlation was observed between the enantioselectivity of the Pd-catalyzed reaction and the steric bulk of the silyl groups in 1.…”

“…Tetrahydrofuran and hexane (homogenized with tetraglyme) were distilled from benzophenoneketyl under an atmosphere of nitrogen prior to use. The second generation Grubbs catalyst, [14] 1,4-disilyl-2-butenes (6a-c), [13] 3-bromo-5-trimethylsilylpenta-1,3-diene (1a), [12] [PdCl(π-allyl)] 2 , [20] dpbp, [15] Pd(dba) 2 , [21] (R)-segphos, [16] (S)-tBu-segphos, [17] tBuCH-(OMe) 2 , [22] and (MeO) 2 CHCH 2 CH(CO 2 Me) 2 [23] were prepared as reported. All other chemicals were obtained from commercial sources and used without additional purification.…”