A process for the preparation of a α-hydroxyketone or α-aminoketone from 1,1-dicarbo substituted oxirane,
- wherein the 1,1-dicarbo substituted oxirane is a compound of the formula II
- wherein n ranges from 1 to 4;
- A1, if n is 1, is carbocyclic aryl which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, Aro, and/or by alkyl, alkoxy, alkenyl or alkenyloxy, each of which itself is unsubstituted or substituted by OPr, halogen, NR9R10, carboxy, Aro, COR1, SO2R2, nitro, CN;
- or is carbocyclic aryl substituted by O—R8—O—SiR11R12R13;
- or A1 is alkyl, alkenyl, alkoxy, alkenyloxy, each of which is unsubstituted or substituted by OPr, halogen, NR9R10, Aro, COR1, OCOR3, NR9COR3, and/or, if having at least 3 carbon atoms, can be interrupted in a carbon-carbon single bond by O, NR9, COO, CONR9;
- or A1 is hydrogen;
- A1, if n is 2, is Ar—R5—Ar;
- or is a residue R11R12Si(O—R8—O—Ar)2;
- or A1 is a direct bond;
- A1, if n is 3, is a residue (Ar)3—R6;
- or is a residue R11Si(O—R8—O—Ar)3;
- A1, if n is 4, is a residue (Ar)4—R7;
- A2 and A3 independently are alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, alkylaryl, arylalkyl, cycloalkylalkyl, or one of said residues substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN;
- and/or, if having at least 3 carbon atoms, are interrupted in a carbon-carbon single bond by O, NR9, COO, OCONR9, CONR9;
- or A2 and A3 together are C4-C11alkylene, -oxaalkylene, -azaalkylene or -alkenylene, each of which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, and/or by alkyl, alkoxy, alkenyl, alkenyloxy, each of which itself is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN;
- Ar stands for a divalent carbocyclic aryl which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, Aro, alkyl, alkoxy;
- Aro stands for aryloxy which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, alkyl, alkoxy, alkenyl, alkenyloxy;
- Pr stands for hydrogen or a protecting group;
- R1 is hydrogen, OH, alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl, alkylphenyl, alkoxyphenyl, alkoxy, alkenoxy, cycloalkoxy, cycloalkenoxy, phenoxy, alkylphenoxy, alkoxyphenoxy;
- R2 is OH, alkyl or alkoxy;
- R3 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl, alkylphenyl, alkoxyphenyl;
- R4 and R′4 independently are hydrogen, C1-C12alkyl or cyclohexyl;
- R5 is a direct bond;
- a heteroatomic spacer selected from —O—, —NR9—, —S—, —SO—, SO2—, CO, COO;
- C1-C18alkylene;
- C3-C18alkenylene;
- or C1-C18-alkylene interrupted or end-capped by —O—, —NR9—, —S—, —SO—, SO2—, CO, COO, CONR9, OCONR9, OCOO, cyclohexylene, phenylene and/or substituted by OPr or NR9R10;
- or R5 is a tri- or tetravalent C3-C12alkyl moiety with 2 of its chemical bonds attached to one Ar and its 3rd and, if present, 4th chemical bond attached to the other Ar moiety;
- R6 is C2-C18-alkane-triyl optionally interrupted or end-capped by —O—, —NR9—, —S—, —SO—, SO2—, CO, COO, CONR9, OCONR9, OCOO, cyclohexylene, phenylene, and which is unsubstituted or substituted by OPr or NR9R10;
- or is C3-C18alkene-triyl;
- R7 is C2-C18-alkane-tetryl optionally interrupted or end-capped by —O—, —NR9—, —S—, —SO—, SO2—, CO, COO, CONR9, OCONR9, OCOO, cyclohexylene, phenylene, and which is unsubstituted or substituted by OPr or NR9R10;
- or is C4-C18alkene-tetryl;
- R8 is a divalent aliphatic or cycloaliphatic residue;
- R9 and R10 independently are hydrogen, C1-C12alkyl, C1-C12alkyl substituted by OPr and/or NR4R′4, C5-C12cycloalkyl;
- or R9 and R10 are joined together to form a tetramethylene, pentamethylene, oxatetramethylene or oxapentamethylene moiety;
- R11, R12 and R13 independently are C1-C12alkyl or C1-C12alkoxy, which process comprises the steps of:
- ii) reacting a sulphonium salt conforming to the formula
- wherein R is alkyl of 1 to 20 carbon atoms, which is unsubstituted or substituted by C5-C12cycloalkyl or phenyl, and R′ is as defined for R or is C5-C12cycloalkyl, phenyl, phenyl substituted by C1-C12alkyl;
- or R and R′ together are penta- or hexamethylene, which may be substituted by C1-C12alkyl or phenyl;
- A1 is an aromatic organic carbon anchor group;
- and
- X′− is a suitable anion;
- with a ketone in presence of a base and a polar solvent, and then subsequently converting the 1,1-dicarbo substituted oxirane into an α-hydroxyketone or α-aminoketone,
- wherein the α-hydroxyketone or α-aminoketone is of the formula I′
- wherein
- n ranges from 1 to 4;
- A1, if n is 1, is carbocyclic aryl which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, Aro, and/or by alkyl, alkoxy, alkenyl or alkenyloxy, each of which itself is unsubstituted or substituted by OPr, halogen, NR9R10, carboxy, Aro, COR1, SO2R2, nitro, CN;
- or is carbocyclic aryl substituted by O—R8—O—SiR11R12R13;
- A1, if n is 2, is Ar—R5—Ar;
- or is a residue R11R12Si(O—R8—O—Ar)2;
- A1, if n is 3, is a residue (Ar)3—R6;
- or is a residue R11Si(O—R8—O—Ar)3;
- A1, if n is 4, is a residue (Ar)4—R7;
- A2 and A3 independently are alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, alkylaryl, arylalkyl, cycloalkylalkyl, or one of said residues substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN;
- and/or, if having at least 3 carbon atoms, are interrupted in a carbon-carbon single bond by O, NR9, COO, OCONR9, CONR9;
- or A2 and A3 together are C4-C11alkylene, -oxaalkylene, -azaalkylene or -alkenylene, each of which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, and/or by alkyl, alkoxy, alkenyl, alkenyloxy, each of which itself is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN;
- Ar stands for a divalent carbocyclic aryl which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, Aro, alkyl, alkoxy;
- Aro stands for aryloxy which is unsubstituted or substituted by OPr, NR9R10, carboxy, COR1, SO2R2, halogen, nitro, CN, alkyl, alkoxy, alkenyl, alkenyloxy;
- Pr stands for hydrogen or a protecting group;
- D is OH;
- R1 is hydrogen, OH, alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl, alkylphenyl, alkoxyphenyl, alkoxy, alkenoxy, cycloalkoxy, cycloalkenoxy, phenoxy, alkylphenoxy, alkoxyphenoxy;
- R2 is OH, alkyl or alkoxy;
- R3 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl, alkylphenyl, alkoxyphenyl;
- R4 and R′4 independently are hydrogen, C1-C12alkyl or cyclohexyl;
- R5 is a direct bond;
- a heteroatomic spacer selected from —O—, —NR—, —S—, —SO—, SO2—, CO, COO;
- C1-C18 alkylene;
- C3-C18 alkenylene;
- or C1-C18-alkylene interrupted or end-capped by —O—, —NR—, —S—, —SO—, SO2—, CO, COO, CONR9, OCONR9, OCOO, cyclohexylene, phenylene and/or substituted by OPr or NR9R10;
- or R5 is a tri- or tetravalent C3-C12alkyl moiety with 2 of its chemical bonds attached to one Ar and its 3rd and, if present, 4th chemical bond attached to the other Ar moiety;
- R6 is C2-C18-alkane-triyl optionally interrupted or end-capped by —O—, —NR9—, —S—, —SO—, SO2—, CO, COO, CONR9, OCONR9, OCOO, cyclohexylene, phenylene, and which is unsubstituted or substituted by OPr or NR9R10;
- or is C3-C18alkene-triyl;
- R7 is C2-C18-alkane-tetryl optionally interrupted or end-capped by —O—, —NR9—, —S—, —SO—, SO2—, CO, COO, CONR9, OCONR9, OCOO, cyclohexylene, phenylene, and which is unsubstituted or substituted by OPr or NR9R10;
- or is C4-C18alkene-tetryl;
- R8 is a divalent aliphatic or cycloaliphatic residue;
- R9 and R10 independently are hydrogen, C1-C12alkyl, C1-C12alkyl substituted by OPr and/or NR4R′4, C5-C12cycloalkyl;
- or R9 and R10 are joined together to form a tetramethylene, pentamethylene, oxatetramethylene or oxapentamethylene moiety;
- R11, R12 and R13 independently are C1-C12alkyl or C1-C12alkoxy;
- R18 and R19, independently, are selected from H, C1-C4alkyl, or are joined together to form a tetramethylene, pentamethylene, oxatetramethylene, oxapentamethylene, or to form an azatetramethylene or azapentamethylene moiety, wherein the nitrogen atom is unsubstituted or is substituted by C1-C4alkyl.