Catalytic systems for stereoselective synthesis of chiral amines by enantiodivergent radical C—H amination
In one aspect, the disclosure relates to a mode of asymmetric induction in radical processes based on sequential combination of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution. Also disclosed is an asymmetric system for stereoselective synthesis of strained 5-membered cyclic sulfamides via radical 1,5-C—H amination of sulfamoyl azides. The disclosed metalloradical system can control the degree and sense of asymmetric induction in the catalytic radical C—H amination in a systematic manner. The disclosed system is applicable to a broad scope of substrates with different types of C(sp 3 )—H bonds and exhibits reactivity and selectivity, providing access to both enantiomers of useful 5-membered cyclic sulfamides in a highly enantioenriched form. Also disclosed are catalysts useful in these 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 stereoselective synthesis of chiral sulfamides, the catalyst having Formula I:
wherein M comprises cobalt;
wherein m is 1;
wherein R 1 is selected from
and
wherein each R 2 and R 2 ′ is independently —CH 2 — and each R 2 is chemically linked to an adjoining R 2 ′ with a bridge having a structure
wherein n is 0, 2, 4, or 6.
2. The catalyst of claim 1 , wherein n is 4 and R 1 is
3. The catalyst of claim 1 , wherein n is 2 and R 1 is
4. A method for the stereoselective synthesis of a chiral sulfamide, the method comprising contacting a sulfamoyl azide substrate with the catalyst of claim 1 in a solvent.
5. The method of claim 4 , wherein the solvent comprises methyl tert-butyl ether (MTBE).
6. The method of claim 4 , wherein the substrate has Formula II:
wherein R 3 is a benzoyl group, and
wherein R 4 is selected from:
or wherein R 3 is —(CH 2 ) 3 -Ph and R 4 is -Ph.
7. The method of claim 6 , wherein the chiral sulfamide consists of the following structures:
8. The method of claim 7 , wherein the ratio of (R) enantiomer at * to (S) enantiomer at * is from about 4:96 to about 99:1.