Over the last 20 years, small molecule hydrogen bond donors have emerged as important catalysts in enantioselective organic synthesis.[1] During this time, chiral organocatalysts dominated the landscape of H-bond donor catalysis. Noting that certain chiral motifs are difficult to access in organic catalysts, Gladysz and his co-workers at Texas A&M sought to expand the chiral pool to include inorganic transition metal complexes. Inspired by the helically chiral surface of D3-symmetric Werner complexes [Co(en)3]3+, the team utilized the classic structural motif with the added stereochemical enforcement of chiral (S,S)-1,2-diphenylethylenediamine ligands (dpen).[2-4] Accordingly, 27-4010 and 27-4011 (Figure 1) represent two diastereomeric isomers of the [Co((S,S)-dpen)3]3+ enantiomers—symbolized as Λ and Δ, respectively. In these complexes, metal-centered chirality is effectively anchored by N-coordination of the amine groups with Co3+. Notwithstanding, primary coordination of the amine does not prevent substrates from organizing at the catalyst surface through [N-H ∙ ∙ ∙ substrate] hydrogen bonding interactions.[2-4]
Figure 1. H-bond donor catalysts with axial symmetry (each of the twelve H-bond donating groups in blue).
Hydrogen bonding of the catalysts with various substrates has been shown to promote a diverse range of enantioselective transformations including C-C, C-heteroatom and C-H bond formation. As shown in Figure 2, L-[Co((S,S)-dpen)3]3Cl2BArF4 (27-4010) was found to catalyze enantioselective Michael reaction between malonate esters and nitroalkenes.[3]
Figure 2. Enantioselective Michael addition of malonate esters with nitroalkenes catalyzed by 27-4010.
The diastereomer Δ-[Co((S,S)-dpen)3]3Cl2BArF20 (27-4011) was found to serve as an efficient catalyst in enantioselective α-aminations of 1,3-dicarbonyl compounds with di-tert-butyl azodicarboxylate in the presence of N-methylmorpholine (NNM). Evaluation of a variety of substrates showed efficient conversion of five- and six-membered ring ketones (99-88% yields, >99-91% ee), 2-cyanocyclopentanone (92%, 45% ee), and an acyclic oxybutanoate (98%, >99% ee).[2]
Figure 3. Enantioselective α-aminations catalyzed by 27-4011.
Gladysz’s [Co(dpen)3][2Cl][BAr4] catalysts are readily soluble in organic solvents and offer excellent functional group tolerance while delivering high levels of enantioselectivity for a diverse range of applications. The catalysts are not air-sensitive and can be used under ambient conditions. In addition to applications in catalysis, [Co(en)3]3+ complexes have been used to resolve enantiomers for analysis by NMR.[5]
References:
Products mentioned in this blog:
27-4010: lambda-Tris[(1S,2S)-1,2-diphenyl-1,2-ethanediamine]cobalt(III) chloride tetrakis[3,5-bis(trifluoromethyl)phenyl]borate dihydrate SKJ-1 [1542135-29-4]
27-4011: delta-Tris[(1S,2S)-1,2-diphenyl-1,2-ethanediamine]cobalt(III) chloride tetrakis(2,3,4,5,6-pentafluorophenyl)borate trihydrate SKJ-3 [1867120-15-7]