Cross-coupling of phenolic derivatives
Embodiments of the invention provide methods and materials for chemical cross-coupling reactions that utilize unconventional phenol derivatives as cross-coupling partners. Embodiments of the invention can be used to synthesize a variety of useful organic compounds, for example the anti-inflammatory drug flurbiprofen.
1. A method for making a cross-coupled compound comprising:
combining together:
(1) an organoboron compound consisting essentially of an organoboronic acid, a diorganoborinic acid, a organoboronate ester, an organoboroxine, a organotrialkoxyborate, an organotrifluoroborate, an organotrihydroxyborate, a tetraorganoborate, a triorganoborane, an alkylborane or a tetrafluoroborate compound;
(2) an aryl alcohol derivative having the structure:
wherein R consists essentially of
an acyl moiety;
a carbamoyl moiety;
a carboxyl moiety;
a sulfamoyl moiety; or
a phosphoryl moiety; and
(3) a transition metal catalyst, wherein the transition metallic catalyst comprises nickel or palladium;
wherein (1), (2) and (3) are combined so as to allow a cross-coupling reaction that results in the formation of the cross-coupled compound in a yield of at least 25%;
so that the cross-coupled compound is made.
2. The method of claim 1 , wherein the cross-coupling reaction results in the formation of the cross-coupled compound in a yield of at least 50%.
3. The method of claim 1 , wherein the cross-coupled compound is formed from a one-pot synthesis.
4. The method of claim 1 , wherein the transition metallic catalyst comprises nickel.
5. The method of claim 1 , wherein the transition metal catalyst comprises an air stable Ni(II) precatalyst complex prior to its combination with (1) and (2).
6. The method of claim 1 , wherein the transition metal catalyst is regenerated simultaneously with formation of the cross-coupled compound.
7. The method of claim 1 , wherein the cross-coupled compound is formed via a Suzuki-Miyaura cross-coupling reaction.
8. A method for performing a Suzuki-Miyaura cross-coupling reaction comprising:
combining together:
(1) an organoboron compound consisting essentially of an organoboronic acid, a diorganoborinic acid, a organoboronate ester, an organoboroxine, a organotrialkoxyborate, an organotrifluoroborate, an organotrihydroxyborate, a tetraorganoborate, a triorganoborane, an alkylborane or a tetrafluoroborate compound;
(2) an aryl alcohol derivative having the structure:
wherein R consists essentially of:
an acyl moiety;
a carbamoyl moiety;
a carboxyl moiety;
a sulfamoyl moiety; or
a phosphoryl moiety; and
(3) a transition metal catalyst, wherein the transition metallic catalyst comprises nickel or palladium;
wherein (1), (2) and (3) are combined so as to allow:
oxidative addition of the transition metal catalyst and generation of a first organo-transition metal species;
reaction between the first organo-transition metal species and the organoboron compound and generation of a second organo-transition metal species; and
reductive elimination of the second organo-transition metal species, regeneration of the transition metal catalyst and generation of a cross-coupled compound in a yield of at least 25%;
so that a Suzuki-Miyaura cross-coupling reaction is performed.
9. The method of claim 8 , wherein the reaction produces the cross-coupled compound in a yield of at least 50%.
10. The method of claim 8 , wherein the organoboron compound comprises an arylboronic acid compound.
11. The method of claim 8 , wherein the metallic catalyst comprises nickel and the organo-transition metal species comprises an organo-nickel species.
12. The method of claim 8 , wherein the reaction is performed as a one-pot synthesis.
13. The method of claim 8 , wherein the Suzuki-Miyaura cross-coupling reaction is not performed in a glovebox.
14. The method of claim 8 , wherein the transition metal catalyst comprises an air stable Ni(II) precatalyst complex immediately prior to its combination with the organoboron compound and (2).
15. The method of claim 8 , further comprising performing a base mediated hydrolysis on the cross-coupled compound.
16. The method of claim 15 , wherein the cross-coupled compound is an intermediate in the synthesis of flurbiprofen.