Compositions and methods for catalysts based on bridged chiral amidoporphyrins and their metal complexes
In one aspect, the disclosure relates to a mode of asymmetric induction in radical processes based on enhanced hydrogen-bonding capability and the situation of metal centers in cavity-like chiral environments. Also disclosed is an asymmetric system for stereoselective synthesis of cyclopropane and aziridine derivatives. The disclosed Co(II)-based metalloradical system has been shown to have an unusual capability of controlling both the degree and sense of asymmetric induction in cyclopropanation and aziridination reactions in a systematic manner. The disclosed system is applicable to a broad scope of substrates having diazo or azido moieties and exhibits a remarkable profile of reactivity and selectivity, providing access to cyclopropane diastereomers and aziridine enantiomers in highly enantioenriched forms. Also disclosed are catalysts useful in the disclosed processes. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
1. A catalyst for the synthesis of chiral cyclopropane derivatives and chiral aziridine derivatives, the catalyst comprising Formula I:
wherein R 10a and R 10b are
wherein R 20a and R 20b are hydrogen; wherein each of R 30a , R 30b , R 30c , R 30d , R 30e , and R 30f are hydrogen; wherein n is 1 or 2; and wherein M is cobalt.
2. The catalyst of claim 1 , wherein stereocenters in the catalyst have the (R) configuration.
3. The catalyst of claim 1 , wherein n is 1.
4. The catalyst of claim 1 , wherein n is 2.
5. A method for the stereoselective synthesis of a chiral cyclopropane derivative, the method comprising contacting a diazo substrate and a vinyl-containing substrate with the catalyst of claim 1 in a solvent and wherein the solvent comprises toluene, chlorobenzene, or a combination thereof.
6. The method of claim 5 , wherein the diazo substrate comprises ethyl diazoacetate and wherein the vinyl-containing substrate comprises styrene.
7. The method of claim 5 , wherein the chiral cyclopropane derivative comprises a structure of Formula III:
wherein R 100 is C1-C10 substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl, and substituted heteroalkyl; wherein R 200 is —(C═O)R 40 ; wherein R 40 is selected from substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl, and substituted heteroalkyl, —NR 41 R 42 , —OR 41 , —SR 41 ; and herein each of R 41 and R 42 is independently selected from hydrogen, substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl, and substituted heteroalkyl.
8. The method of claim 7 , wherein the structure of Formula III comprises:
9. The method of claim 7 , wherein the ratio of (R) enantiomer at * to (S) enantiomer at * is from about 5:95 to about 95:5.
10. The method of claim 7 , wherein the ratio of (R) enantiomer at ** to (S) enantiomer at ** is from about 5:95 to about 95:5.
11. The method of claim 7 , wherein the chiral cyclopropane derivative comprises a mixture of diastereomers and wherein the mixture of diastereomers comprises at least 80% of a compound having (R) configuration at * and **.
12. A method for the stereoselective synthesis of a chiral aziridine derivative, the method comprising contacting an azido-containing substrate and a vinyl-containing substrate with the catalyst of claim 1 in a solvent and wherein the solvent comprises toluene, chlorobenzene, or a combination thereof.
13. The method of claim 12 , wherein the azido-containing substrate comprises trichloroethoxysulfonyl azide and wherein the vinyl-containing substrate comprises styrene.
14. The method of claim 12 , wherein the chiral aziridine derivative comprises a structure of Formula IV:
wherein R 300 is C1-C10 substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl, and substituted heteroalkyl; wherein R 400 is —(C═O)R 40 ; wherein R 40 is selected from substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl, and substituted heteroalkyl, —NR 41 R 42 , —OR 41 , —SR 41 ; and herein each of R 41 and R 42 is independently selected from hydrogen, substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl, and substituted heteroalkyl.
15. The method of claim 14 , wherein the structure of Formula IV comprises:
16. The method of claim 14 , wherein the ratio of (R) enantiomer at *** to (S) enantiomer at*** is from about 5:95 to about 95:5.