Aminohydroxylation of alkenes
The invention relates to a process for the aminohydroxylation of alkenes using N-oxycarbamate reagents, e.g. N-acyloxycarbamate, N-alkyloxycarbonyloxycarbamate and N-aralkoxycarbonyloxycarbamate reagents. The invention particularly relates to an intermolecular aminohydroxylation reaction that can be carried out in the absence of added base. The invention also relates to novel N-oxycarbamate reagents that are stable crystalline materials. The process of the invention is useful in the synthesis of compounds having a vicinal amino alcohol moiety, such as biologically active compounds.
1. A process for preparing a β-hydroxycarbamate compound form an alkene, using an aminohydroxylation reaction, the process including the step of:
reacting the alkene with an N-oxycarbamate compound, in the presence of an osmium compound as a catalyst, to give the β-hydroxycarbamate compound;
where the process is carried out in the absence of added base and where the N-oxycarbamate compound is a compound of formula (II):
where
R 3 is an optionally substituted alkyl group, an optionally substituted aralkyl group or an optionally substituted aryl group;
R 4 is a radical of formula (ii)
or R 4 is OR 5 ;
R 2 is halogen, alkyl, alkoxy, dialkylamino, trialkylammonium, nitro, carboxy alkyl ester, alkylamide, —SO 3 H, —PO 3 H 2 or —COOH, where, when n is greater than 1, each R 2 is independently selected;
R 5 is an optionally substituted alkyl group or an optionally substituted aralkyl group; and
n is 0, 1, 2, 3, 4 or 5;
provided that the following compounds are excluded:
the compound where: R 3 is t-butyl; R 4 is a radical of formula (ii) where R 2 is Cl and n is 3; and
the compound where: R 3 is t-butyl; R 4 is a radical of formula (ii) where R 2 is methyl and n is 3.
2. A process as claimed in claim 1 wherein the N-oxycarbamate is an N-acyloxycarbamate compound of formula (I):
wherein:
R 1 is a radical of formula (iii)
R 3 is an optionally substituted alkyl group, an optionally substituted aralkyl group or an optionally substituted aryl group;
provided that the following compounds are excluded:
the compound where: R 1 is a radical of formula (iii) where R 3 is t-butyl; R 2 is Cl and n is 3; and
the compound where: R 1 is a radical of formula (iii) where R 3 is t-butyl; R 2 is methyl and n is 3.
3. A process as claimed in claim 1 , wherein the N-oxycarbamate is an N-alkyloxycarbonyloxycarbamate or an N-aralkoxycarbonyloxycarbamate compound of formula (III):
wherein:
R 5 is an optionally substituted alkyl group or an optionally substituted aralkyl group; and
R 6 is an optionally substituted alkyl group or an optionally substituted aralkyl group.
4. A process according to claim 1 , wherein the osmium catalyst is osmium tetroxide, potassium osmate(VI) dehydrate, osmium(III) trichloride or an immobilized osmium catalyst.
5. A process according to claim 1 wherein the reaction of the alkene and the N-oxycarbamate, N-acyloxycarbamate, N-alkyloxycarbonyloxycarbamate or N-aralkoxycarbonyloxycarbamate compound is carried out in an organic solvent containing water.
6. A process as claimed in claim 2 wherein the reaction of the alkene and the N-acyloxycarbamate compound is carried out in the presence of a chiral ligand.
7. A process as claimed in claim 6 where the chiral ligand is (DHQ) 2 PHAL, (DHQD) 2 PHAL or (DHQ) 2 AQN.
8. A process as claimed in claim 1 wherein the reaction of the alkene and the N-oxycarbamate, N-acyloxycarbamate, N-alkyloxycarbonyloxycarbamate or N-aralkoxycarbonyloxycarbamate compound is carried out in a mixed solvent system selected from the group consisting of acetonitrile/water, isopropanol/water, t-butanol/water, acetone/water, tetrahydrofuran/water, dioxane/water and dimethylformamide/water.
9. A process as claimed in claim 1 wherein R 2 is a halogen.
10. A process as claimed in claim 2 R 1 is EtO 2 C, MeO 2 C, 2-trimethylsilylethoxycarbonyl, phenoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, benzyloxycarbonyl, t-butoxycarbonyl or 9fluorenylmethoxycarbonyl.
11. A process as claimed in claim 1 wherein n is 1.
12. A process as claimed in claim 1 wherein R 5 is ethyl, tert-butyl, 9-fluorenylmethyl or benzyl.
13. A process as claimed in claim 3 wherein R 5 and R 6 are the same.
14. A process as claimed in claim 1 wherein the N-oxycarbamate compound is an N-acyloxycarbamate compound selected from the group consisting of:
15. A process as claimed in claim 1 wherein the N-oxycarbamate compound is an N-alkyloxycarbonyloxycarbamate or N-aralkoxycarbonyloxycarbamate compound selected from the group consisting of:
16. A compound selected from the group consisting of: