Process for the electrophilic substitution of thiazolidines or oxazolidines
View Patent ↗A process for preparing α-functionalized thiazolidines or oxazolidines, each of which are oxycarbonyl-functionalized in the 4-position, by adding a base to a reaction mixture comprising an oxycarbonyl-functionalized thiazolidine or oxazolidine and an electrophile at a temperature of greater than −40° C.
1. A process for preparing compounds of the general formula (2)
where
X is S or O and
R 1 is selected from the group consisting of hydrogen, metals of the first or second main group, linear or branched C 1 –C 12 -alkyl, C 6 –C 15 -aryl or C 7 –C 21 -aralkyl radicals, dialkylsilyl and trialkylsilyl, dialkylarylsilyl, diarylalkylsilyl, triarylsilyl radicals, and the organic radicals of the silyl radicals are in turn selected from C 1 –C 12 -alkyl and C 6 –C 15 -aryl radicals and
R 2 is selected from the group consisting of linear or branched C 1 –C 12 -alkyl, C 6 –C 15 -aryl and C 7 –C 21 -aralkyl radicals and
P is an amino protecting group and
E is a radical selected from the group consisting of optionally halogen, cyano, nitro or ester group-substituted, linear or branched C 1 –C 12 -alkyl, C 3 –C 10 -alkenyl, C 6 –C 15 -aryl and C 7 –C 21 -aralkyl radicals, or is an acyl or formyl group,
comprising adding a base to a reaction mixture comprising a compound of the general formula (1)
and an electrophile E-Y
where
Y is a leaving group,
and carrying out the reaction at a temperature of greater than −40° C.
2. A process for preparing optical isomers in the configuration of the general formula (2a)
using optical isomers of the general formulae (1a) or (1b) in pure form or as mixtures
where
X is S or O and
R 1 is selected from the group consisting of hydrogen, metals of the first or second main group, linear or branched C 1 –C 12 -alkyl, C 6 –C 15 -aryl or C 7 –C 21 -aralkyl radicals, dialkylsilyl and trialkylsilyl, dialkylarylsilyl, diarylalkylsilyl, triarylsilyl radicals, and the organic radicals of the silyl radicals are in turn selected from C 1 –C 12 -alkyl and C 6 –C 15 -aryl radicals and
R 2 is selected from the group comprising linear or branched C 1 –C 12 -alkyl, C 6 –C 15 -aryl and C 7 –C 21 -aralkyl radicals and
P is an amino protecting group and
E is a radical selected from the group consisting of optionally halogen, cyano, nitro or ester groupsubstituted, linear or branched C 1 –C 12 -alkyl, C 3 –C 10 -alkenyl, C 6 –C 15 -aryl and C 7 –C 21 -aralkyl radicals, or is an acyl or formyl group,
comprising adding a base to a reaction mixture comprising a compound of the general formula (1)
and an electrophile E-Y
where
Y is a leaving group,
and carrying out the reaction at a temperature of greater than −40° C.
3. The process of claim 1 , wherein P is selected from the group consisting of alkyl, formyl, acyl, oxycarbonyl, sulfonyl, sulfenyl and silyl radicals.
4. The process of claim 1 , wherein Y is selected from the group consisting of halogens, tosylates, azides, hydrazides, dialkylamides and sulfonates.
5. The process of claim 1 , wherein the base is an alkali metal amide.
6. The process of claim 1 , wherein E-Y is methyl iodide or dimethyl sulfate.
7. The process of claim 1 , wherein the process is carried out at a temperature of from −30° C. to +30° C.
8. The process of claim 1 , wherein R 1 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, phenyl, benzyl, trimethylsilyl, triethylsilyl and tributylsilyl.
9. The process of claim 1 , wherein R 2 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclohexyl, phenyl, tolyl, naphthyl and benzyl.
10. The process of claim 2 , wherein P is selected from the group consisting of alkyl, formyl, acyl, oxycarbonyl, sulfonyl, sulfenyl and silyl radicals.
11. The process of claim 2 , wherein Y is selected from the group consisting of halogens, tosylates, azides, hydrazides, dialkylamides and sulfonates.
12. The process of claim 2 , wherein the base is an alkali metal amide.
13. The process of claim 2 , wherein E-Y is methyl iodide or dimethyl sulfate.
14. The process of claim 2 , wherein the process is carried out at a temperature of from −30° C. to +30° C.
15. The process of claim 2 , wherein R 1 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, nbutyl, tert-butyl, phenyl, benzyl, trimethylsilyl, triethylsilyl and tributylsilyl.
16. The process of claim 2 , wherein R 2 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclohexyl, phenyl, tolyl, naphthyl and benzyl.