US 8,263,798 B2 · Optically active quaternary ammonium salt having axial asymmetry, and method for producing alpha-amino acid and derivative thereof by using the same

Abstract

The present invention discloses an optically active quarternary ammonium salt having axial asymmetry and a method for producing an α-amino acid and a derivative thereof using the same. The optically active quarternary ammonium salt having axial asymmetry of the present invention is a chiral phase-transfer catalyst that has a simple structure and that can be produced in a smaller number of process steps. The compound of the present invention is very useful as a phase-transfer catalyst in the synthesis of an α-alkyl-α-amino acid and a derivative thereof as well as an α,α-dialkyl-α-amino acid and a derivative thereof. Therefore, the compound of the present invention can be used in the development of novel foods and pharmaceuticals.

A method for producing an optically active α-amino acid, comprising:

alkylating a compound represented by Formula (IV):
with a compound of Formula (V):
R18—W (V)
to give a compound represented by Formula (VI):
using a compound represented by Formula (I) that is pure with respect to its axial asymmetry as a phase-transfer catalyst:
in a medium in the presence of an inorganic base,
hydrolyzing an imino group (R14R15C═N—) of a compound represented by Formula (VI):
under acidic conditions, and
hydrolyzing an ester group (—CO2R17) of the acidic-hydrolysis product under acidic or basic conditions,
wherein in Formula (I),
R2 and R2′ are each independently:
a hydrogen atom;
or
an aryl group, wherein the aryl group may be substituted with at least one group selected from the group consisting of:
a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom,
a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom,
an aryl group that may be substituted with a halogen atom or a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom, and
a halogen atom;
R3 and R3′ are each independently:
a C1 to C5 alkoxy group that may be substituted with a halogen atom and/or an aryl group, and/or that may be branched or form a cyclic group;
R4 and R4′ are each independently a group selected from the group consisting of:
(i) a hydrogen atom;
(ii) a halogen atom;
(iii) a C1 to C6 alkyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom;
(iv) a C2 to C6 alkenyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom;
(v) a C2 to C6 alkynyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom;
(vi) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be substituted with at least one group selected from the group consisting of:
a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom,
a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom,
an aryl group that may be substituted with a halogen atom or a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom, and
a halogen atom;
and
(vii) an aryl group, wherein the aryl group may be substituted with at least one group selected from the group consisting of:
a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom,
a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom,
an aryl group that may be substituted with a halogen atom or a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom, and
a halogen atom;
R7 and R8 are each independently a monovalent organic group, or
R7 and R8 are taken together to form a divalent organic group, and
X−is a halide anion;
in Formulae (IV) and (VI),
R14 and R15 are each independently:
(i) a hydrogen atom;
or
(ii) an aryl group, wherein the aryl group may be substituted with at least one group selected from the group consisting of:
a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom,
a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom,
an aryl group that may be substituted with a halogen atom or a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom, and
a halogen atom,
with the proviso that a case where R14 and R15 are both hydrogen atoms is excluded;
R16 is a group selected from the group consisting of:
(i) a hydrogen atom;
(ii) a C1 to C10 alkyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom, wherein the alkyl group may be substituted with a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom;
(iii) a C2 to C6 alkenyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom;
(iv) a C2 to C6 alkynyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom;
(v) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be substituted with at least one group selected from the group consisting of:
a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom,
a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom,
an aryl group that may be substituted with a halogen atom or a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom, and
a halogen atom;
and
(vi) an aryl group, wherein the aryl group may be substituted with at least one group selected from the group consisting of:
a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom,
a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom,
an aryl group that may be substituted with a halogen atom or a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom, and
a halogen atom;
and
R17 is a C1 to C8 alkyl group that may be branched or form a cyclic group,
in Formulae (V) and (VI),
R18 is a group selected from the group consisting of:
(i) a C1 to C10 alkyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom, wherein the alkyl group may be substituted with a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom;
(ii) a C2 to C6 alkenyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom;
(iii) a C2 to C6 alkynyl group that may be branched or form a cyclic group and that may be substituted with a halogen atom;
(iv) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be substituted with at least one group selected from the group consisting of:
a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom,
a C1 to C5 alkoxy group that may be branched and that may be substituted with a halogen atom,
an aryl group that may be substituted with a halogen atom or a C1 to C4 alkyl group that may be branched and that may be substituted with a halogen atom, and
a halogen atom;
and
(v) a C3 to C9 propargyl group or substituted propargyl group that may be branched and that may be substituted with a halogen atom,
in Formula (V),
W is a functional group having a leaving ability, and
in Formula (VI),
* indicates a newly produced asymmetric center.

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Optically active quaternary ammonium salt having axial asymmetry, and method for producing alpha-amino acid and derivative thereof by using the same

Life of this patent

Optically active quaternary ammonium salt having axial asymmetry, and method for producing alpha-amino acid and derivative thereof by using the same

Life of this patent

Abstract

Claims26