Quaternary heteroatom containing compounds
A compound useful as a building block for the manufacture of various compounds is represented by Formula A or D. In Formula A and D, z is 0 or 1; Q is a heteroatom; R1 through R11 and Ra through Rf are each independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom containing hydrocarbyl group, or a functional group; d, e and f are each independently 0 or greater; each of A, B and D is independently a carbon atom or a heteroatom; and two or more of R1 though R11, Ra through Rf and Y optionally combine to form a ring. In some embodiments, R8 and R9 combine to form a carbonyl group. In some embodiments, R2 and Y combine to form a ring with the Q atom. In some embodiments, the ring includes at least one double bond.
1. A method of making an enantioenriched heteroatom-containing compound, the method comprising subjecting a compound of Formula A to palladium-catalyzed decarboxylative alkylation using an electron-poor ligand, a palladium-based catalyst, and a solvent:
wherein:
z is 1;
Q is N;
each of R 1 through R 10 is independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom-containing hydrocarbyl group, or a functional group;
Y is hydrogen, a heteroatom, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom-containing hydrocarbyl group, or a functional group; and
two or more groups selected from R 1 through R 10 and Y optionally combine to form a ring or a carbonyl group.
2. The method of claim 1 , wherein the electron-poor ligand comprises a ligand including an electron-poor moiety selected from the group consisting of fluorine atoms, partially or fully fluorinated hydrocarbyl groups, partially or fully fluorinated heteroatom-containing hydrocarbyl groups, NO 2 groups and SO 2 R groups, wherein R is hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom-containing hydrocarbyl group, or a functional group.
3. The method of claim 1 , wherein the electron-poor ligand comprises a R′-PHOX ligand, wherein R′ is selected from the group consisting of (CF 3 ) 3 groups, partially or fully fluorinated hydrocarbyl groups, partially or fully fluorinated heteroatom-containing hydrocarbyl groups, NO 2 groups and SO 2 R groups, wherein R is hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom-containing hydrocarbyl group, or a functional group.
4. The method of claim 1 , wherein R 8 and R 9 combine to form a carbonyl group.
5. The method of claim 1 , wherein R 2 and Y combine to form a ring with Q, the ring including between 3 and 12 atoms.
6. The method of claim 5 , wherein the ring includes between 4 and 7 ring atoms.
7. The method of claim 1 , wherein R 2 and Y combine to form a ring including at least one double bond.
8. The method of claim 1 , wherein R 1 is an amine-protecting group.
9. The method of claim 1 , wherein R 1 is OH.
10. The method of claim 1 , wherein the compound of Formula A is a compound represented by Formula C:
wherein:
z is 1;
each of d, e and f is independently an integer of 0 or greater;
Q 1 is N;
each of A, B and D is independently a heteroatom or a carbon atom, and an A atom that is directly adjacent the Q 1 atom is not a chiral center; and
each of R a through R f is either:
independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom-containing hydrocarbyl group, or a functional group; or
combines with another of R a through R f to form a double bond or a carbonyl group.
11. The method of claim 10 , wherein R 8 and R 9 combine to form a carbonyl group such that the compound of Formula C is represented by Formula C(i):
12. The method of claim 10 , wherein R 1 and one R a combine to form a double bond, or one R b and one R c combine to form a double bond, or one R d and one R e combine to form a double bond.
13. The method of claim 10 , wherein one R a and one R b combine to form a carbonyl group, or one R c and one R d combine to form a carbonyl group, or one R e and one R f combine to form a carbonyl group.
14. The method of claim 1 , wherein the enantioenriched heteroatom-containing compound is selected from:
15. The method of claim 1 , wherein the enantioenriched heteroatom-containing compound has an enantiomeric excess of greater than 50%.
16. The method of claim 1 , wherein the enantioenriched heteroatom-containing compound has an enantiomeric excess of about 70% or greater.