Design and Synthesis of Novel Chiral Dirhodium(II) Carboxylate Complexes for Asymmetric Cyclopropanation Reactions

Abstract

A novel approach to the design of dirhodium(II) tetracarboxylates derived from (S)-amino acid ligands is reported. The approach is founded on tailoring the steric influences of the overall catalyst structure by reducing the local symmetry of the ligand's N-heterocyclic tether. The application of the new approach has led to the uncovering of [Rh (S- PTTL) ] as a new member of the dirhodium(II) family with extraordinary selectivity in cyclopropanation reactions. The stereoselectivity of [Rh (S- PTTL) ] was found to be comparable to that of [Rh (S-PTAD) ] (up to >99 % ee), with the extra benefit of being more synthetically accessible. Correlations based on X-ray structures to justify the observed enantioinduction are also discussed.

Chiral Dirhodium(II) Carboxylates: New Insights into the Effect of Ligand Stereo-Purity on Catalyst Structure and Enantioselectivity

“…Out of the large dirhodium(II) catalyst family and by following different approaches for catalyst design, several highly enantioselective dirhodium(II) carboxylate catalysts have been reported to date [13,[35][36][37][38][39][40][41][42][43][44]. Our research group, for example, has recently reported a novel approach for the design of dirhodium(II) tetracarboxylate complexes derived from S-amino acid ligands [35,36,45].…”

“…Our research group, for example, has recently reported a novel approach for the design of dirhodium(II) tetracarboxylate complexes derived from S-amino acid ligands [35,36,45]. This approach is founded on tailoring the steric influences of the overall catalyst structure through reducing the local symmetry of the ligand's N-heterocyclic tether.…”

“…This approach is founded on tailoring the steric influences of the overall catalyst structure through reducing the local symmetry of the ligand's N-heterocyclic tether. The application of this new approach led to the uncovering of Rh 2 (S-tert PTTL) 4 (Figure 1) as a new member to the dirhodium(II) family with outstanding selectivity in asymmetric cyclopropanation reactions [35]. However, despite the number of successful approaches used for catalyst design, limited evidence is still available on how the four chiral carboxylate ligands within the dirhodium(II) carboxylate framework tailor the product chirality at the catalyst active center [46].…”

“…In the case of published X-ray crystal structures of various solvated adducts of Rh 2 (S-PTTL) 4 [47,48], Rh 2 (S-tert PTTL) 4 [35], Rh 2 (S-NTTL) 4 [49], Rh 2 (S-PTAD) 4 [35] and others [35,50,51], the incorporation of a ligand stereogenic center begets a "chiral cavity" or a "chiral pocket". Figure 2 [47,48] depicts the two most important features that are responsible for the establishment of the chiral binding pocket in Rh 2 (S-PTTL) 4 and related complexes; C-C bond torsion (bond connecting carboxylate carbon to α-carbon) that is positioned so as to guide the C-N single bond leading to a clockwise twist of the chiral cavity walls (Figure 2a), and C-N bond torsion (bond units (featuring alternating O ... H-C closest contacts, Figure 2c).…”

“…Figure 2 [47,48] depicts the two most important features that are responsible for the establishment of the chiral binding pocket in Rh 2 (S-PTTL) 4 and related complexes; C-C bond torsion (bond connecting carboxylate carbon to α-carbon) that is positioned so as to guide the C-N single bond leading to a clockwise twist of the chiral cavity walls (Figure 2a), and C-N bond torsion (bond units (featuring alternating O ... H-C closest contacts, Figure 2c). The overall visual result is that the eight oxygen atoms of the ligands' N-phthaloyl units are placed at alternate high and low positions around the periphery of the carbene binding pocket (Figure 2b) [35]. Based on these observed features, the use of optically pure ligands in the process of catalyst preparation is essential for the construction of the symmetric chiral cavity and for achieving extremely reliable enantioselective catalysis [52].…”