Compositions for reductive aminations utilizing supported tricarboxyborohydride reagents and methods of using the same
A modified solid-support for use as a supported reagent for use in reduction reactions, including reductive amination comprising a solid-support having an tetrasubstituted ammonium cation species ionically bonded to a borohydride anion species extending therefrom having the general formula: wherein P is a solid-support, S is a spacer group selected from the group consisting of alkylene, {including —(CH 2 ) n —}, alkyleneoxy {including -0(CH 2 ) n —}, alkylenethio {including —S(CH 2 ) n —} and alkylenecarboxy, {including —O(O)C—(CH2) n —}, n=2-16. R 1 , R 2 , R 3 and R are each independently selected from the group consisting of alkyl, cycloalkyl, haloalkyl and aryl. Y equals 1, 2 or 3. H is hydrogen or deuterium.
1. A modified solid-support for reduction reactions which comprises: a solid-support having a tetrasubstituted ammonium cation species ionically bonded to a borohydride anion species extending there from having the general formula:
wherein
P is a solid-support, which is a macroporous polystyrene, and S is an alkylene spacer R 1 , R 2 , and R 3 are each ethyl, R is methyl, Y equals 3, H is hydrogen or deuterium; and
an organic solvent wherein said organic solvent is tetrahydrofuran (THF) and stabilizes said solid-supported reagent during storage.
2. A modified solid support according to claim 1 wherein the solid-supported reagent comprising the THF has a higher activity than a solid-supported reagent in which the solvent is removed.
3. A modified solid-support according to claim 1 wherein said tetrahydrofuran is from about 1.3 to 25 wt %.
4. A modified solid support according to claim 1 wherein the amount of said THF is about 1.3 wt % to about 30 wt %.
5. A modified solid support according to claim 1 wherein the amount of said THF is about 3 wt % to about 30 wt %.
6. A modified solid support according to claim 1 wherein the amount of said THF is about 10 wt %.
7. A modified solid support according to claim 1 wherein the amount of said THF is about 25 wt %.
8. A method for synthesizing a modified solid-support of claim 2 for use in solid phase synthesis comprising:
providing a solid-support of a macroporous methylpolystyrene having a triethylammonium borohydride group extending therefrom;
exposing the solid-support with a solution containing THF and acetic acid;
performing a substitution reaction whereby three of the hydrogen atoms bonded to the boron atom is exchanged for an acetate group; and
removing the solution until less than 30 wt % of the THF remains.
9. A modified solid support according to claim 1 wherein the solid-supported reagent comprising the THF has a higher activity at 6 days of storage than a solid-supported reagent in which the solvent is removed.
10. A modified solid support according to claim 1 wherein the solid-supported reagent comprising the THF has a higher activity at 30 days of storage than a solid-supported reagent in which the solvent is removed.
11. A modified solid support according to claim 1 wherein S is methylene.
12. A method of conducting an organic synthesis reduction reaction, which comprises reacting reagents for an organic synthesis reduction in the presence of the modified solid support of claim 2 .
13. A method of reductively aminating a carbonyl group, which comprises reacting reagents for reductive amination of a carbonyl group in the presence of the modified solid support of claim 2 .
14. A method of reductively alkylating an amino group, which comprises reacting reagents for reductive alkylation of an amino group in the presence of the modified solid support of claim 2 .