Evolution of Metal Complex‐Catalysts by Dynamic Templating with Transition State Analogs

Abstract

The elicitation of hydrolytic catalysts from a dynamic library of imine‐zinc(II) complexes (and their precursor aldehydes and amines) via templating with pro‐transition state analogs (pro‐TSA) is described. pro‐TSA (2‐pyridyl)phosphonate 2 amplifies a benzimidazole‐derived complex at the expense of an imidazole analogue; the amplified complex is also more active for the hydrolysis of the pyridyl ester 1a. Employing pro‐TSA pyridyl hydrate 3 with libraries of Zn complexes of imines having nucleophilic side chains also perturbs the library in favor of imine‐Zn complexes which prove to be the more active hydrolytic agents and catalysts. The catalytichydrolyses exhibit both saturation kinetics and inhibition by the pro‐TSA. This process for catalyst evolution is operationally simple, amenable to high throughput screening, potentially applicable to a wide variety of catalytic reactions and thus could offer a practical alternative to catalytic antibodies and imprinted polymers.

Regioselectivity in the Cu(I)-Catalyzed [4 + 2]-Cycloaddition of 2-Nitrosopyridine with Unsymmetrical Dienes

“…30−32 We have developed a new method for catalyst selection based on the expected correlation between the binding affinity of transitionstate analogues (TSAs) to a catalyst and the catalyst's activity and selectivity (Figure 1). 33 As applied to selectivity control, the use of regio-or stereoisomeric TSAs in a dynamic combinatorial templating process 34−39 could allow the elicitation of catalysts selective for the product derived from the TSA employed. In our recent work, we have demonstrated the viability and efficacy of the dynamic templating strategy for the elicitation of hydrolytic Zn catalysts.…”

A Forty Year Odyssey in Metallo–Organic Chemistry

“…We established a proof-of-concept and successfully applied this strategy for the identification of Zn(imine) catalysts for pyridine ester hydrolysis with a gem-diol TSA 14 (Figure 15 a,b). 81 To enable high-throughput catalyst selection, we have shown the viability of MS analysis of metal complex mixtures for semiquantitative TSA−ML n binding 82 and we have evaluated the dynamic templating approach for the identification of metal catalysts for the kinetic resolution of esters 81 and regioselective nitroso-arene hetero-Diels−Alder reactions (Figure 16). 83 A simple affinity chromatographic method for metal-complex catalyst selection is currently being investigated in which the TSA or a substrate analogue is bound to the chromatographic support.…”

“…We established a proof-of-concept and successfully applied this strategy for the identification of Zn­(imine) catalysts for pyridine ester hydrolysis with a gem -diol TSA 14 (Figure a,b) . To enable high-throughput catalyst selection, we have shown the viability of MS analysis of metal complex mixtures for semiquantitative TSA–ML n binding and we have evaluated the dynamic templating approach for the identification of metal catalysts for the kinetic resolution of esters and regioselective nitroso-arene hetero-Diels–Alder reactions (Figure ) .…”

An efficient dynamic asymmetric catalytic system within a zinc-templated network

“…[4][5][6] A few other examples have been subsequently developed using alternative approaches, essentially reversible imine formation. [7][8][9][10][11] However, none of them dealt with controlling the stereoselectivity of the catalytic reaction. Thus, there is lack of important knowledge in this field.…”