WO1996021507A1

WO1996021507A1 - Catalyst for asymmetric diels-alder reactions

Info

Publication number: WO1996021507A1
Application number: PCT/US1996/000090
Authority: WO
Inventors: Won S. Park
Original assignee: Albemarle Corporation
Priority date: 1995-01-09
Filing date: 1996-01-11
Publication date: 1996-07-18

Abstract

Catalyst prepared according to the formula (1): 2 A1H3 + Ar(-OH)2 + 2Rc-OH + 2HC1; where Rc is a chiral alcohol selected from the group consisting of diacetone-D-glucose, diacetone-D-allofuranose, norborneol, isocamphenol and menthol and Ar is chiral diol whose chirality is caused by restricted rotation about a single bond. These catalytic compounds are useful in catalyzing asymmetric Diels-Alder reactions.

Description

CATALYST FOR ASYMMETRIC DIELS-ALDER REACTIONS

Field of Invention

The present invention relates to a new catalyst useful for carrying out an asymmetric Diels- Alder reaction. More particularly, the present invention provides an optically active aluminum catalyst useful in such Diels- Alder reaction.

Background of the Invention

Enantioselective catalysis using chiral metal complexes provides one of the most general and flexible methods for achieving asymmetric organic reactions. Metallic elements possess a variety of catalytic activities, and permutations of organic ligands or other auxiliary groups directing the steric course of the reaction are practically unlimited. Efficient ligands must be endowed with, for example, suitable functionality, appropriate chirality, a structure capable of differentiating space either electronically or sterically and skeletal rigidity or flexibility.

Among the asymmetric organic reactions catalyzed by chiral transition metal complexes, asymmetric hydrogenation has been one of the best studied, due in large part to the fact that it is the basis for the first commercialized catalytic asymmetric process. See, for example, ApSimon, et al., Tetrahedron. 1986, 42, 5157.

Some of the more interesting of the asymmetric hydrogenation catalysts are those derived from BINAP [2,2'-bis(diphenylphosphino)-lJ,'-binaphthyl]. See, for example, U.S. Pat. Nos.: 4,691,037; 4,739,084; 4,739,085; 4,764,629; 4,994,607; and 4,766,277. Unlike the more classical models of chiral (asymmetric) molecules, chirality in the case of the BINAP compounds arises from the restricted rotation about the single bond joining the naphthalene rings. Isomers arising from this type of asymmetry are termed atropisomers.

BINAP-based Ru(II) and Rh(I) complexes induce high enantioselectivity in catalytic reactions. See Noyori and Takaya, Ace. Chem. Res.. 1990, 23, 345. The use of BINAP as a metal complexing reagent in asymmetric reactions other than hydrogenation was reported by Narasaka et al., Chem. Lett. (1986) 1967 (and also see Narasaka et al., Chem. Lett. (1987) 2409). In this report, the Diels-Alder reaction of 1,3-dienes and conformationally rigid dienophiles prepared from reacting α,β-unsaturated acids with l,3-oxazolidin-2-one was catalyzed by a BINAP titanium complex to produce the cycloadducts in high enantiomeric excess (ee).

In a former study, Chapuis et al., J. Helv. Chim Acta (1987) 7_Ω, 437, described the use of chiral Lewis acids prepared in situ from EtAlCl₂ and chiral diols (in a 2: 1 ratio) or a sulfonamide (in a 1:1 ratio). Enantiomeric excesses up to 98% for the cycloadduct were achieved when the Diels-Alder reaction was performed with the bidentate dienophile BINAP bearing an oxazolidinone moiety. However, there was no report on the possible use of a catalytic amount of chiral complex, and the system was restricted to the bidentate crotonate dienophile.

A hetero Diels-Alder reaction has been performed in the presence of racemic complex of aluminum with BINAP and (+)-3-bromocamphor (0.3 mol equiv each). Cis- dihydropyrone was isolated with ee up to 80% (instead of 95% ee with pure (S) complex). Maruaka et al., J. Am. Chem. Soc. 111. 789 (1984). Previously small ee's in hetero Diels-Alder reaction with menthoxydichloroaluminum as the chiral catalyst had been reported. Quimfere et al., J. Chem. Soc. Chem. Commun., 676 (1987).

Summary

The present invention relates to a novel chiral catalyst prepared from an aluminum hydride, a chiral alcohol and an atropisomer of a diol. The catalyst is a chiral complex and is useful for carrying out an asymmetric Diels-Alder reaction of dienes with dienophiles. Description of the Preferred Embodiments

In the present specification, alkyl means straight or branched chain alkyl having 1 to 20 carbon atoms and includes, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl, tertiary butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, 2-ethylhexyl, 1,1,3,3-tetramethylbutyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, and eicosyl.

Cycloalkyl means cyclic alkyl having 3 to 7 carbon atoms and includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

Substituted aryl means phenyl or naphthyl substituted by a least one substituent selected from the group consisting of halogen (chlorine, bromine, fluorine or iodine), amino, nitro, hydroxy, alkyl, alkoxy, which means straight or branched chain alkoxy having 1 to 10 carbon atoms, and includes, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, secondary butoxy, tertiary butoxy, pentyloxy, isopentyloxy, haloalkyl which means straight or alkyl having 1 to 8 carbon atoms which is substituted by at least one halogen, and includes, for example, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, 2-chloroethyl, 2-bromoethyl, 2-fluoroethyl, 3- chloropropyl, 3-bromopropyl, 3-fluoropropyl, 4-chlorobutyl, 4-fluorobutyl, dichloromethyl, dibromomethyl, difluoromethyl, diiodomethyl, 2,2-dichloroethyl, 2,2- dibromoethyl, 2,2-difluoroethyl, 3,3-dichloropropyl, 3,3-difluoropropyl, 4,4- dichlorobutyl, 4,4-difluorobutyl, trichloromethyl, trifluoromethyl, 2,2,2-trifluoroethyl,

2,3,3-trifluoroproρyl, 1,1,2,2-tetrafluoroethyl and 2,2,3, 3-tetτafluoropropyl.

Haloalkyl means straight or branched chain alkyl having 1 to 10 carbon atoms which is substituted by at least one halogen as mentioned above.

Phenylalkyl means that the alkyl moiety is straight or branched chain alkyl having 1 to 8 carbon atoms and include, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3- phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl and 8-phenyloctyl.

Substituted phenylalkyl means above-mentioned phenylalkyl which is substituted by at least one substituted selected from the group consisting of halogen, amino, nitro, hydroxy, alkyl, alkoxy and haloalkyl on the phenyl nucleus.

The chiral complex catalyst of use in the asymmetric Diels-Alder reaction according to the present invention is prepared according to the following reaction:

2A1H₃ + Ar(-OH)₂ + 2R.-OH + 2HC1 (1)

The expected species of the reaction product is:

where Ar(-OH)₂ is a chiral aryl diol having restricted rotation about a single bond (a atropisomer) and

R_<.OH is a chiral alcohol that is not Ar(OH)₂.

An especially preferred catalyst in accordance with reaction (1) of the presen invention is where,

Ar(-OH)₂ is (-)-2,2-Bi-l-naphthol and R,.OH is diacetone-D-glucose.

Another especially preferred catalyst in the reaction (1) is one where Ar(-OH)₂

and

R_cOH is a compound of the formula:

where R is C, to C₆ linear or branched alkyl, phenyl, substituted phenyl, to C₆ linear or branched alkoxy or halo, Ar is phenyl. The most convenient route for the preparation of the above chiral diol starts with the Diels-Alder reaction of anthracene with vinylene carbonate to form compound of the following formula

where R is as previously defined. The cyclic carbonate is easily hydrolyzed to the cis- diol (using, for example, aqueous base).

The chiral diols having restricted rotation about a single bond within the molecule include bicyclic diols, binaphthyl diols, bipyrryl diols, biphenyl diols, paracyclophane diols, etc. It is preferred, however, that the chiral diols are binaphthyl diols, either substituted or unsubstituted. Particularly preferred are binaphthyl compounds of the formula

where R_A and R_B are the same or different and are alkyl. Illustrative of such binaphthy diol compounds are the following: 1,1 '-binaphthyl diol; δ.δ'-dimethyl-U'-binaphthyl diol 5,5'-dimethyl-l, -binaphthyl diol;

As a further reactant in the preparation of the catalysts of this invention, a chiral alcohol is also employed. While any chiral alcohol is useful in the preparation of these catalysts, preferably the chiral alcohols include those compounds whose chirality is due to the presence of an asymmetric carbon atom to which the -OH moiety is attached or to those bicyclic alcohols where rotation is restricted because of the ring. Particularly preferred chiral alcohols include the enantiomers of diacetone-D-glucose, diacetone-D-allofuranose, norborneol, isocamphenol, hydroquinine, 2-hydroxy-3-methylbutyric acid, ethyl ester, 2- hydroxy-4-phenylbutyric acid, ethyl ester, etc.

The chiral catalysts of the present invention are typically prepared by first reacting sodium aluminum hydride with a complex formed of hydrogen chloride and diethyl ether in a polar, aprotic solvent, such as tetrahydrofuran. The reaction is a well-known method for preparing aluminum hydride. See, for example. Cha et al.. J. Org. Chem.. 58.(15).

3974 (1993). The aluminum hydride solution is subsequently used to treat the chiral diol. A preferred mole ratio of hydride to diol is 2 to 1, which results in a solution of partially complexed aluminum bearing a still-reactive hydride atom. This hydride is readily replaced by reactions with the chiral alcohol and a solution of hydrogen chloride/diethyl ether. The course of these reactions is easily followed by monitoring the hydrogen gas evolution. Complete reactions (yields are typically in excess of 90%) for additions of the diol, the chiral alcohol, and hydrogen chloride/diethyl ether occur readily at room temperature. The solid catalyst obtained after evaporation of solvent is used directly in subsequent reactions as suspensions in non-polar solvent according to a further embodiment of the present invention.

A preferred embodiment of the process utilized to prepare the chiral catalyst in accordance with the present invention is where the solvent is tetrahydrofuran, the temperature is 25 °C, the pressure is atmospheric and the atmosphere under which the reaction is carried out consists essentially of solvent vapors. Argon or nitrogen can also be used as inert gases over the reaction mixture during the reaction process.

As earlier noted, the catalyst composition of the invention offers an improve process for carrying out a Diels-Alder reaction to provide the 1,4-addition of a diene to second component, a dienophile, including contacting a mixture of the chiral Diels-Alde catalyst and the diene and dienophile, either neat or in an inert solvent, in an ine atmosphere.

Prior art processes for catalytically coupling dienes to dienophiles using chir catalysts are known in the art and are described in Kagan et al., Chem. Rev.. _ , 1007

1019 (1982) and in Scheffeld, Ed, Modern Synthetic Methods. £, 115-197, Springe Verlag, Heidelberg 1989, in which the respective reactants and conditions for suc reactions are incorporated herein by reference.

Details regarding the process with respect to typical solvents used, proces conducted under neat conditions, catalyst concentration, substrate concentration, reactio temperature range, pressure, methods of isolation and purification, yields and selectivitie of products in the processes are all described in the prior art and need not be reiterate herein.

The novelty of this improved process is the discovery that the subject composition are surprisingly effective catalysts for the respective asymmetric catalysis of Diels-Alde reactions, even in the case of hindered dienophiles, such as 2-methyl-2-cyclopentene-l-on or 2-methyl-2-cyclohexene-l-one.

Preferred dienes for use in the reaction are 1 ,4-disubstituted linear dienes and 1 ,4 optionally substituted cyclic dienes as well as 2,3-dimethylbutadiene, 2-methy 1-1,3 butadiene, and cyclopentadiene.

Preferred dienophiles are in the form

-Z—Z—l o r Z— C=C— Z '

where Z and Z' are individually -CHO, -COR, -COOH, -COOR, -COC1, -COAr, -CN

NO₂, -Ar, -CH₂OH, -CH₂C1, -CH₂NH₂, -CH₂CN, -CH₂COOH, halogen, or cyclopenta-2-ene-l-one or cyclohexa-1-ene-l-one. The following examples are for the purpose of illustration only and are not intended to limit the scope of the present invention.

EXAMPLES A1H, -I- 1/2 BINOL + DADG + HCl: fin-situ. System A A1H₃ in THF showed complete evoluion of stoichiometric amount hydrogen on east step, when treated with 2,2'-bi-l-naphthol (one-half equivalent), diacetone-D-glucose, and with HCl, successively. When the Diels-Alder reaction of 2-methyl-2-cyclopentene-l-one (MCPN) with isoprene was carried out using the resulting catalyst system (equimolar amount) as a suspension in toluene at 70°C (standard condition), 86% conversion and 79% yield of the Diels-Alder resulted in 4 days. 2,5-dimethylhydroindanone (1) and 2,4,- dimethylhydroindanone (2) was produced in 90:10. The major product, 2,5- dimethylhydroindanone, analyzed to have 8-14% ee on a chiral GC using a Chiraldex G- TA column from Astec Inc. Examples are listed in Table 1.

TABLE 1

A1H, + 1/2 BINOI. 4- DADG System

Claims

1. An optically active Diels Alder catalyst prepared according to the formula

2A1H₃ + Ar(OH)₂ -I- 2R_cOH + 2HC1

where -R-OH is a chiral alcohol selected from the group consisting of diacetone-D- glucose, diacetone-D-allofiiranose, norbomeol, isocamphenol and menthol and Ar(OH)₂ is chiral diol whose chirality is caused by restricted rotation about a single bond.

2. The compound according to claim 1 wherein said chiral diol is selected from the group consisting of bicyclic diol, binaphthyl diol, bipyrryl diol, biphenyl diol and paracycloxane diol.

3. The compound according to claim 2 where said chiral diol is a binaphthyl diol.

4. The compound according to claim 3 wherein said chiral alcohol is diacetone-D-glucose .

5. The compound according to claim 2 wherein said chiral diol is a bicyclic diol.

6. The compound according to claim 6 wherein said chiral alcohol is diacetone-D-glucose .

7. In the catalyzed, asymmetric Diels-Alder reaction of the 1 ,4-addition of a diene to a dienophile, the improvement comprising carrying out said reaction in the presence of a catalytically effective amount of an optically active compound prepared according to the following reaction: 2A1H₃ + Ar(-OH)₂ + 2R.OH + 2HC1

where R_e is a chiral alcohol selected from the group consisting of diacetone-D-glucose, diacetone-D-allofuranose, norbomeol, isocamphenol and menthol and Ar is chiral diol whose chirality is caused by restricted rotation about a single bond.

8. The reaction according to claim 7 wherein said chiral diol is selected from the group consisting of bicyclic diol, binaphthyl diol, bipyrryl diol, biphenyl diol and paracycloxane diol.

9. The reaction according to claim 8 where said chiral diol is a binaphthyl diol.

10. The reaction according to claim 9 wherein said chiral alcohol is diacetone-D-glucose .

11. The reaction according to claim 8 wherein said chiral diol is a bicyclic diol.

12. The reaction according to claim 11 wherein said chiral alcohol is diacetone-D-glucose.

13. The improved reaction according to claim 7 where the diene is isoprene and the dienophile is hindered cyclic alkenones, like 2-methyl-2-cyclopenten-l-one, 2- methyl-2-cyclohexen-l-one, etc.