Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2002-09-03
2003-07-01
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S873000, C568S855000
Reexamination Certificate
active
06586644
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a process for producing optically active propargyl alcohols useful as synthetic intermediates for medicines, agricultural chemicals or the like. In more detail, it relates to a process for producing optically active propargyl alcohols in which an aldehyde compound and a terminal acetylene are reacted in the presence of an optically active amino alcohol, using a zinc halogenated lower alkane sulfonate as the catalyst.
PRIOR ARTS
Propargyl alcohols have been used as intermediates for various kinds of chemicals. Particularly, increasing their biological activities from their racemates, optically active propargyl alcohols have been known as useful intermediates for medicines, agricultural chemicals, polymeric materials or the like, and efficient production methods of the optically active compounds have been desired to be developed.
As a process for producing optically active propargyl alcohols, there have been reported processes in which a stoichiometric quantity of metal acetylide is added to an aldehyde or a ketone enantioselectively (Journal of American Chemical Society 1994, 116, 3151-3152, Journal of American Chemical Society 1998, 120, 2028). Among other, the processes in which a zinc acetylide is used as the metal acetylide, have been reported many. However, in such a process, a stoichiometric or more quantity of zinc dialkylate, which is unstable in the air, is generally used as the zinc acetylide (Synthesis 1999, 1453-1458, Chem. Rev. 1992, 92, 833-856.). In addition to the above, a process in which an acetylene and an aldehyde are reacted in the presence of an optically active N-methylephedrine and a stoichiometric quantity of zinc containing compound has been known as a process for producing optically active propargyl alcohols (Journal of American Chemical Society 2000, 122, 1806-1807, Organic Letters2000, 2,4233-4236.).
According to the above processes, however, still a sufficient yield of optically active propargyl alcohol and a sufficient enantioselectivity (optical yield) have not been attained, and a production process capable of attaining higher yield and enatioselectivity is desired to be developed.
Further, the above-mentioned known production processes require a stoichiometric quantity of metal reagent, and amount of the used metal is not a truly catalytic quantity. Therefore, it is also desired that the reaction system volume and the amount of starting materials required for the product are made as small as possible, amount of materials to be used and disposals are reduced, and the volumetrically efficiency and atomic economy are improved.
An object of the present invention is to provide a process for producing optically active propargyl alcohols, wherein the metal compound is used in an amount of less than equivalent molar, that is, a truly catalytic quantity of metal is used, and whereby a high yield and a high enantioselectivity of the objective optically active propargyl alcohol can be attained, and the volumetrically efficiency and atomic economy are improved, reducing amount of materials to be used and disposals.
The present inventors have found that, in a process for producing optically active propargyl alcohols by reacting an aldehyde compound and a terminal acetylene in the presence of an optically active amino alcohol, using a zinc halogenated lower alkane sulfonate as the catalyst, when the aldehyde and the terminal acetylene are those having specific structures, (1) the reaction can be carried out even in the absence of solvent or in a small amount of solvent and even by using a zinc halogenated lower alkane sulfonate in an amount of less than equivalent molar, and, as the results, high volumetrically efficiency and atomic economy can be attained, and (2) high yield and a high enatioselectivity of the produced optically active propargyl alcohol can be attained. The present invention was completed based on these findings.
SUMMARY OF THE INVENTION
The present invention provides a process for producing an optically active propargyl alcohol represented by the following formula (4):
wherein
R
1
is an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, an alkynyl group, an alkylsilyl group, an aromatic hydrocarbon group, a C2-C10 heterocyclic group having 1-3 heteroatoms or a C1-C10 alkyl group having 1-3 heteroatoms, provided that
the alkyl group, the cycloalkyl group, the alkenyl group, the cycloalkenyl group, the alkynyl group, the alkylsilyl group and the C1-C10 alkyl group having 1-3 heteroatoms are unsubstituted or substituted by 1-3 substituents selected from halogen atoms, hydroxyl groups, carboxyl groups, carbonyloxyalkyl groups which may be optionally substituted, carbonyloxyaryl groups which may be optionally substituted, nitro groups, alkyl groups, alkenyl groups, cycloalkyl groups, cycloalkenyl groups, aralkyl groups, alkoxy groups, di-substituted amino groups, aryl groups which may be optionally substituted, C2-C10 heterocyclic groups having 1-3 heteroatoms, C1-C10 alkyl groups having 1-3 heteroatoms and alkylsilyloxy groups, and
the aromatic hydrocarbon group and the C2-C10 heterocyclic group having 1-3 heteroatom are unsubstituted or substituted by 1-3 substituents selected from halogen atoms, hydroxyl groups, carboxyl groups, carbonyloxyalkyl groups which may be optionally substituted, carbonyloxyaryl groups which may be optionally substituted, nitro groups, alkyl groups, alkenyl groups, cycloalkyl groups, cycloalkenyl groups, aralkyl groups, alkoxy groups, amino groups, C1-C10 alkyl groups having 1-3 heteroatoms and alkylsilyloxy groups; and
R
2
is an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, an alkynyl group, an alkylsilyl group, an aromatic hydrocarbon group, a C2-C10 heterocyclic group having 1-3 heteroatoms or a C1-C10 alkyl group having 1-3 heteroatoms, provided that
the alkyl group, the cycloalkyl group, the alkenyl group, the cycloalkenyl group, the alkynyl group, the alkylsilyl group, and the C1-C10 alkyl group having 1-3 heteroatoms are unsubstituted or substituted by 1-3 substituents selected from halogen atoms, hydroxyl groups, carboxyl groups, carbonyloxyalkyl groups which may be optionally substituted, carbonyloxyaryl groups which may be optionally substituted, nitro groups, alkyl groups, alkanyl groups, cycloalkyl groups, cycloalkenyl groups, aralkyl groups, acyloxy groups, alkoxy groups, amino groups, groups represented by —ORa wherein Ra represents a C2-C10 heterocyclic group having 1-3 heteroatoms, aryl groups which may be optionally substituted, C2-C10 heterocyclic groups having 1-3 heteroatoms, C1-C10 alkyl groups having 1-3 heteroatoms and alkylsilyloxy groups, and
the aromatic hydrocarbon group and the C2-C10 heterocyclic group having 1-3 heteroatoms are unsubstituted or substituted by 1-3 substituents selected from halogen atoms, hydroxyl groups, carboxyl groups, carbonyloxyalkyl groups which may be optionally substituted, carbonyloxyaryl groups which may be optionally substituted, nitro groups, alkyl groups, alkenyl groups, cycloalkyl groups, cycloalkenyl groups, aralkyl groups, alkoxy groups, amino groups, C1-C10 alkyl groups having 1-3 heteroatoms and alkylsilyloxy groups;
which comprises allowing an aldehyde compound represented by the following formula (1).
R
1
—CHO (1)
wherein R
1
means as defined above,
to react with an alkyne compound represented by the following formula (2):
HC≡—C—R
2
(2)
wherein R
2
means as defined above;
in the presence of an optically active aminoalcohol represented by the following formula (3):
wherein
R
3
, R
4
, R
5
and R
6
each independently are a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkynyl group, a C1-C6 alkylsilyl group, a C3-C12 cycloalkyl group, a C2-C10 cyclic amine group or a C6-C10 aryl group, which are unsubstituted or substituted by a C1-C10 alkyl group, a C6-C10 aryl group, a nitro group, an amino group, a halogen atom, a sulfide group or a sulfonyl group, provided that optional two of R
3
, R
4
, R
5
and R
6
may toget
Barts Samuel
Carreira Erick M.
Fitch Even Tabin & Flannery
Price Elvis O.
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