JPH02223576A - Novel triflate and production of oxygen-containing compound using the same - Google Patents

Abstract

NEW MATERIAL:A triflate expressed by the formula (R and R' are cyclic or acyclic alkyl; n is 1 or 2). USE:Capable of readily synthesizing various optically active substances or cyclic ether compounds and extremely useful for producing the basic skeleton of natural compounds having physiological activity. PREPARATION:A solution of anhydrous trifluoromethanesulfonic acid in anhydrous methylene chloride is dripped into the objective alcohol-anhydrous methylene chloride-pyridine solution at about -15 deg.C in nitrogen atmosphere to afford the compound expressed by the formula. The above-mentioned triflate is used to provide an oxygen-containing compound by triflating alcohols having an oxygen functional group at the beta-position and reacting the resultant compound with an organocopper reagent or reacting the alcohols with a Grignard reagent in the presence of a copper compound catalyst.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention is directed to a novel triflate compound and its use to form ether compounds, particularly medium- and macrocyclic nityl compounds, which are the basic skeleton of certain natural products having physiological activity. The present invention relates to methods for producing various optically active compounds using compounds having this structure and easily available chiral compounds.

[Prior Art and its Problems] Natural products having medium- and macrocyclic ether structures are widely found in nature, and recently, many natural products have been found, especially in marine natural products. These compounds have attracted attention due to their unique structures and physiological activities, and various studies have been conducted on their synthesis.

1solaure, a natural product with a 7-membered ring ether structure
piBacin, a natural product having an 8-membered ring ether structure,
In the production of compounds serving as basic skeletons such as Iaurencin and Iaurepinnacin, a method of introducing a side chain by coupling reaction with a corresponding alcohol can be considered. Generally, in the coupling reaction of alcohols, the hydroxyl group is tosylated or halogenated,
This is accomplished by reacting with an organometallic compound such as a Grignard reagent.

However, in compounds with an oxygen functional group at the β position,
Due to its electron-withdrawing nature, it is extremely difficult for the reaction to proceed.

[Specific Means for Solving the Problems] In view of the above-mentioned problems, the present inventors have made extensive studies and have synthesized various new compounds in which the hydroxyl group is triflated. The present invention was achieved by discovering that when a reaction with a metal compound was carried out, the reaction progressed specifically and easily.

That is, the present invention is based on the general formula % (1) (R, R' represents a cyclic or non-cyclic alkyl group, n
indicates 1 or 2. ) and a method for producing an oxygen-containing compound using the same,
The production method is a method for producing oxygen-containing compounds, which is characterized by triflating an alcohol having an oxygen functional group at the β-position and reacting it with an organocopper reagent or with a Grignard reagent in the presence of a copper compound catalyst. be.

In the present invention, the hydroxyl group may be triflated by a commonly used method. Specifically, a solution of trifluoromethanesulfonic acid anhydride in anhydrous methylene chloride is added to a target alcohol-anhydrous methylene chloride-pyridine solution at -15°C.
drop it over a nitrogen atmosphere to react.

Triflate is obtained from the reaction product by a conventional method, water is removed by azeotropic distillation with toluene, and then the triflate is subjected to the next reaction step.

The coupling reaction for introducing a side chain is performed by reacting the triflate thus obtained with a Grignard reagent or an organic copper reagent, and in the case of a Grignard reagent, it is preferable to use a copper compound as a catalyst.

As the Grignard reagent, commonly used ones such as alkylmagnesium bromide and arylmagnesium bromide can be used as appropriate, and as the organocopper reagent, those prepared from methyllithium or butyllithium can be used, and the necessary All you have to do is choose one that has a side chain.

Ether compounds such as diethyl ether and tetrahydrofuran are preferably used as the solvent for the coupling reaction. In the Campling reaction of the present invention, a copper compound is used as a catalyst, and a monovalent copper compound such as cupric halide is used. The reaction temperature is -30~
It can be in the range of 30°C, more preferably in the range of -10 to 10°C.

Hereinafter, the present invention will be explained in detail with reference to Examples.

Example 1 Trifluoromethanesulfonic anhydride (762 mg, 2.7 mmol) was added to a mixture of 5 ml of methylene chloride, tetrahydropyran-2 methanol (210 mg, 1.8 mmol), and 0.44 ml of pyridine. was added dropwise at 15°C and reacted for 20 minutes under a nitrogen atmosphere to obtain 427 mg of tetrahydropyran-2-methyltrifluoromethanesulfone (tetrahydropyran-2-methyltrifluoromethanesulfone).This was a colorless oil containing Hn m r (CDC13) and IR. The data for (neat) is as follows.

'Hnmr(CDCl2) 61.20-2.10
(6)1. m), 3.30-3.80 (2Hm),
3.90-4.20 (IH, m), 4.40 (2) 1
．． d, J=4.8Hz) IR (neat) 2950
．． 2g50,1410.1240,1200,11.5
0,950760.610 cm-' Then, ice-cooled CuBr (60 mg, 0.42 mm
C, (, H(fig Br (4ml1.2.7mm
Add an anhydrous ether solution of 0+) to the previously obtained triflate of tetrahydropyran-2-methanol (4
27 mg, 1.8 mmol) in tetrahydrofuran (3
ml) was added with stirring at 0°C, and stirring was continued for an additional 2 hours to carry out the reaction. The reaction solution was added to a saturated ammonium chloride solution and purified by flash chromatography to obtain 2-hexyltetrahydropyran (
257 mg, yield 84%).

Examples 2 to 12 Triflate formation was performed in the same manner as in Example 1 to obtain various triflates. Coupling reactions of these triflates were carried out and the results shown in Table 1 were obtained. In the table, tetrahydrofuran was used as the reaction solvent except for Example 3.8, in which diethyl ether was used.

In addition, diethyl ether was used as a solvent for all Grignard reagents. In Example 12, the reaction was carried out at -15°C using Me2CuLi as a reaction reagent. Yield represents the isolated yield after purification.

In addition, the physical properties of the triflates of Example 4 and Example 7, 'H
n m r (CDCl2) and l R (neat
) data are as follows.

Colorless unstable oil 'Hnmr (CDCl2) δ1.6-2.3 (411
, m), 3.6-4.0<2H, m), 4.0-4.
4(IH,m), 4.4-4.6(2H,m)IR(
neat) 2980, 2880, 1410, 124
0,1200,1150,1100950.610c
m' Colorless needle crystals with one branch, melting point 25-27°C [α]2. . -9,14°(C4,90,C)ICl3
)'Hnmr(CDCl2) δ1.45<6H
, s> , 4.15-4.30 (2H, m), 4.50
-4.70 (4H, m) I R (neat) 3000, 2950, 1410
,1200,1150.950,850790.760
．． 600 cm' Comparative Example 1 No CuBr catalyst was used, the reaction temperature was room temperature, and the reaction time was 1
The coupling reaction was carried out in the same manner as in Example 1 except that the reaction time was 8 hours, and the yield was 37%.

[Effects of the Invention] According to the present invention, various optically active substances and cyclic ether compounds can be synthesized into containers, which is extremely useful for producing basic skeletons of physiologically active natural compounds.

Claims (2)

[Claims] (1) General formula R[CH(OR')CH_2OSO_2CF_3]_n
(I) A novel triflate represented by (R and R' represent a cyclic or non-cyclic alkyl group, and n represents 1 or 2). (2) A method for producing an oxygen-containing compound, which comprises triflating an alcohol having an oxygen functional group at the β-position and reacting it with an organic copper reagent or a Grignard reagent in the presence of a copper compound catalyst.