The first chiral ligand library based on self-assembly through complementary hydrogen-bonding was realized. From a 10 x 4 ligand library, catalysts that show excellent activity and enantioselectivity for the asymmetric rhodium-catalyzed hydrogenation have been identified.
Tailor-made ligands are essential for efficient selectivity control in homogeneous metal-complex catalysis. Since the theoretical prediction of an optimal ligand for a given reaction, substrate, and desired selectivity is impossible, combinatorial approaches have emerged to accelerate catalyst discovery.[1] However, these approaches still suffer from limited access to structurally diverse and meaningful ligand libraries. The problem is particularly acute for the important class of bidentate ligands, for which the synthesis, in many cases, involves nontrivial operations that are unsuited for automation. Even more difficult is the synthesis of nonsymmetric bidentate ligands with two different donor sites.As a solution to this problem, we recently introduced an alternative to the classical bidentate-ligand synthesis, the selfassembly of monodentate to bidentate ligands through complementary hydrogen bonding.[2-4] Thus, on the basis of a platform analogous to the A-T base pair, the aminopyridine-isoquinolone system, libraries of achiral and chiral phosphine and phosphonite ligands were evaluated (Scheme 1 a). From these studies, excellent catalysts for regioselective hydroformylation, [5] anti-Markovnikov hydration of alkynes, [6] as well as asymmetric hydrogenation [7] have emerged. In all cases, combinatorial ligand variations were achieved by changing the donor site (Do a/b in Scheme 1 a) on the aminopyridine-isoquinolone platform. It was unclear whether this approach would be restricted to the aminopyridine-isoquinolone self-assembly system, or whether, indeed, a variation of the A-T base-pair analogous platform would also be possible (Scheme 1 b). It was reasonable to expect that any change of the platform geometry or the hydrogen-bonding system would have an immediate impact on the ligand bite angle (q) and the coordination geometry at the metal center, and thus, an important influence on the catalyst performance.[8]Herein, we report on the development of the first library of self-assembled ligands based on new heterocyclic platforms analogous to the A-T base pair. From a first evaluation of this new library of self-assembled phosphine ligands, an extremely regioselective hydroformylation catalyst emerged, in which the ligands behavior was bidentate, even in protic solvents such as methanol.As A-analogous donor-acceptor ligands (L DA in Scheme 1 b), the heterocycle-functionalized phosphines 1-5 were chosen. As T-analogous acceptor-donor ligands (L AD in Scheme 1 b), we selected the known isoquinolone 6 and the new 7-azaindole 7. The preparation of the ligands is described in the Supporting Information.The coordination properties of all 10 possible ligand combinations were studied through the NMR spectroscopic investigation of the corresponding platinum complexes [Cl 2 Pt(L DA )(L AD )] (Table 1). 31 P NMR spectroscopy showed, in all cases, the selective formation of a defined complex with a heterodimeric ligand. In the 31 P NMR spectra, an AB spin system with a 2 J(P,P) coupling constant of 14.8-17.2 Hz was det...
Tailor-made ligands are essential for efficient selectivity control in homogeneous metal-complex catalysis. Since the theoretical prediction of an optimal ligand for a given reaction, substrate, and desired selectivity is impossible, combinatorial approaches have emerged to accelerate catalyst discovery.[1] However, these approaches still suffer from limited access to structurally diverse and meaningful ligand libraries. The problem is particularly acute for the important class of bidentate ligands, for which the synthesis, in many cases, involves nontrivial operations that are unsuited for automation. Even more difficult is the synthesis of nonsymmetric bidentate ligands with two different donor sites.As a solution to this problem, we recently introduced an alternative to the classical bidentate-ligand synthesis, the selfassembly of monodentate to bidentate ligands through complementary hydrogen bonding.[2-4] Thus, on the basis of a platform analogous to the A-T base pair, the aminopyridine-isoquinolone system, libraries of achiral and chiral phosphine and phosphonite ligands were evaluated (Scheme 1 a). From these studies, excellent catalysts for regioselective hydroformylation, [5] anti-Markovnikov hydration of alkynes, [6] as well as asymmetric hydrogenation [7] have emerged. In all cases, combinatorial ligand variations were achieved by changing the donor site (Do a/b in Scheme 1 a) on the aminopyridine-isoquinolone platform. It was unclear whether this approach would be restricted to the aminopyridine-isoquinolone self-assembly system, or whether, indeed, a variation of the A-T base-pair analogous platform would also be possible (Scheme 1 b). It was reasonable to expect that any change of the platform geometry or the hydrogen-bonding system would have an immediate impact on the ligand bite angle (q) and the coordination geometry at the metal center, and thus, an important influence on the catalyst performance.[8]Herein, we report on the development of the first library of self-assembled ligands based on new heterocyclic platforms analogous to the A-T base pair. From a first evaluation of this new library of self-assembled phosphine ligands, an extremely regioselective hydroformylation catalyst emerged, in which the ligands behavior was bidentate, even in protic solvents such as methanol.As A-analogous donor-acceptor ligands (L DA in Scheme 1 b), the heterocycle-functionalized phosphines 1-5 were chosen. As T-analogous acceptor-donor ligands (L AD in Scheme 1 b), we selected the known isoquinolone 6 and the new 7-azaindole 7. The preparation of the ligands is described in the Supporting Information.The coordination properties of all 10 possible ligand combinations were studied through the NMR spectroscopic investigation of the corresponding platinum complexes [Cl 2 Pt(L DA )(L AD )] (Table 1). 31 P NMR spectroscopy showed, in all cases, the selective formation of a defined complex with a heterodimeric ligand. In the 31 P NMR spectra, an AB spin system with a 2 J(P,P) coupling constant of 14.8-17.2 Hz was det...
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