Compounds, reactions, and screening methods
AssigneeThe Board of Trustees of the University of Illiois
InventorsJohn F. HARTWIG, Daniel W. ROBBINS, Seth J. HERZON
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Abstract
The invention provides a method comprising identifying a successful metal-mediated conjugation reaction by analyzing a test mixture for the presence of a conjugation product. The invention provides a two-dimensional approach to reaction discovery in which many catalysts for many catalytic reactions can be tested simultaneously to provide an efficient discovery platform. Reactants and products from the system can be identified using techniques such as gas chromatography, liquid chromatography, mass spectrometry, and combinations thereof.
Claims24
A method comprising heating a test mixture to potentially initiate a metal-mediated conjugation reaction;
- wherein the test mixture initially comprises a combination of seven or more reaction mixtures and optionally one or more control mixtures;
- and
- wherein each reaction mixture comprises a metal catalyst precursor, a ligand, and a diverse mixture of substrates, prior to heating or reaction initiation;
- and
- analyzing the test mixture for the presence of a conjugation product, wherein the mass of any conjugation product formed from a metal-mediated conjugation reaction exceeds the mass of any single substrate of the reaction mixtures by at least about 50%;
- thereby identifying a successful metal-mediated conjugation reaction by the presence of a conjugation product, wherein the presence of a conjugation product in the test mixture confirms that a metal-mediated conjugation reaction occurred in one or more of the reaction mixtures.
A method comprising preparing a compound of Formula I:
- wherein
- R1 is —H, —OH, —(C1-C24)alkyl, —(C1-C24)alkoxy, (C1-C24)acyl, (C1-C24)alkoxycarbonyl, (C1-C24)acyloxy, —CF3, —NO2, —CN, —CHO, or halo;
- n is 1, 2, 3, 4, or 5;
- and
- R2 is (C1-C24)alkyl, aryl, heteroaryl, heterocycle or —SiR′3 where each R′ is independently alkyl, aryl, alkoxy, or aryloxy;
- comprising contacting a compound of Formula II:
- wherein R2 is as defined above for Formula I;
- and a compound of Formula III:
- wherein R1 is as defined above for Formula I;
- in the presence of CuCl or Cu(OAc)2, to provide a reaction mixture, and
- heating the reaction mixture above 25° C., to provide the compound of Formula I.
A method comprising preparing a compound of Formula V:
- wherein
- A is C, N, O, or S;
- m is 1 when A is C, m is 0 when A is O or S, and m is 0 or 1 when A is N;
- R1 is —H, —OH, —(C1-C24)alkyl, —(C1-C24)alkoxy, (C1-C24)acyl, (C1-C24)alkoxycarbonyl, (C1-C24)acyloxy, —CF3, —NO2, —CN, —CHO, or halo;
- or two R1 groups together form a fused benzo, furan, or thiophene ring on the ring of Formula V;
- n is 1, 2, 3, 4, or 5;
- and
- each R3 is independently H, —(C1-C24)alkyl, aryl, heteroaryl, heterocycle, or —SiR′3 where each R′ is independently alkyl, aryl, alkoxy, or aryloxy, provided that both R3 groups are not H;
- comprising contacting a compound of Formula VI:
- wherein R3 is as defined above for Formula V, provided that the compound of Formula VI is a liquid or solid at 23° C.;
- and a compound of Formula VII:
- wherein
- A, m, and R1 are as defined above for Formula V;
- and
- X is B(OH)2, Br, or I;
- in the presence of Ni(cod)2 or NiCl2-dme, and a phosphine ligand or SIPr (1,3-bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazol-3-ium), to provide a reaction mixture;
- and
- heating the reaction mixture above 25° C., to provide the compound of Formula V.
Dependencies are inferred from the claim text.