Ethylaluminum Dichloride1

EtAlCl2

[563-43-9]  · C2H5AlCl2  · Ethylaluminum Dichloride  · (MW 126.95)

(strong Lewis acid that can also act as a proton scavenger; reacts with HX to give ethane and AlCl2X)

Alternate Name: dichloroethylaluminum.

Physical Data: mp 32 °C; bp 115 °C/50 mmHg; d 1.207 g cm-3.

Solubility: sol most organic solvents; stable in alkanes or arenes.

Analysis of Reagent Purity: solutions are reasonably stable but may be titrated before use by one of the standard methods.1e

Form Supplied in: commercially available neat or as solutions in hexane or toluene.

Handling, Storage, and Precautions: must be transferred under inert gas (Ar or N2) to exclude oxygen and water. Use in a fume hood.

Alkylaluminum Halides.

Since the early 1980s, alkylaluminum halides have come into widespread use as Lewis acid catalysts. These strong Lewis acids offer many advantages over traditional metal halide Lewis acids such as Boron Trifluoride, Aluminum Chloride, Titanium(IV) Chloride, and Tin(IV) Chloride. Most importantly, the alkyl group on the aluminum will react with protons to give an alkane and a new Lewis acid. Alkylaluminum halides are therefore Brønsted bases, as well as Lewis acids. The alkyl groups are also nucleophilic, and this is the major disadvantage in the use of these compounds as Lewis acids.

Pure, anhydrous Lewis acids do not catalyze the polymerization of alkenes or the Friedel-Crafts alkylation of aromatics by alkenes. Cocatalysts, such as water or a protic acid, react with the Lewis acid to produce a very strong Brønsted acid that will protonate a double bond. Therefore, use of strictly anhydrous conditions should minimize side reactions in Lewis acid-catalyzed ene, Diels-Alder, and [2 + 2] cycloaddition reactions. Unfortunately, it is difficult to prepare anhydrous, proton-free AlCl3, BF3, etc. Alkylaluminum halides are easily prepared and stored in anhydrous form and, more importantly, scavenge any adventitious water, liberating an alkane and generating a new Lewis acid in the process.

Using alkylaluminum halides, Lewis acid-catalyzed reactions can now be carried out under aprotic conditions. This is of value when side reactions can be caused by the presence of adventitious protons; it is of special value when acidic protons are produced by the reaction. In these cases, use of the appropriate alkylaluminum halide in stoichiometric rather than catalytic amounts gives high yields of products not formed at all with other Lewis acids. The Me2AlCl-catalyzed ene reactions of aliphatic aldehydes with alkenes, which give homoallylic alcohol-Me2AlCl complexes that react further to give methane and the stable methylaluminum alkoxides, is an example of this type of reaction (eq 1).1h,2 Loss of methane prevents the alcohol-Lewis acid complex from solvolyzing or protonating double bonds.

The alkylaluminum halides cover a wide range of acidity. Replacing chlorines with alkyl groups decreases Lewis acidity. EtAlCl2 and Methylaluminum Dichloride are only slightly less acidic than AlCl3. Diethylaluminum Chloride and Dimethylaluminum Chloride are substantially less acidic, and Trimethylaluminum, Me2AlOR, and MeAl(OR)2 are even weaker Lewis acids. Alkylaluminum halides with fractional ratios of alkyl to chloride are also available. The sesquichlorides are commercially available. Other reagents can be prepared by mixing two reagents in the desired proportion. If no reaction occurs with the alkylaluminum halide, a stronger Lewis acid should be tried. If polymerization or other side reactions compete, a weaker Lewis acid should be used. The sequential ene and Prins reactions shown in eq 2 proceed cleanly with Me3Al2Cl3.3 Complex mixtures are obtained with the stronger Lewis acid EtAlCl2 while the weaker Lewis acid Me2AlCl reacts with Formaldehyde to give ethanol.

Use of more than one equivalent of Lewis acid will produce complexes that are formally 1:2 substrate Lewis acid complexes, but are more likely salts with a R2Al-substrate cation and an aluminate anion.4-6 This substrate in this salt is much more electrophilic and reactive than that in simple Lewis acid complexes.

These reagents are easier to use than typical inorganic Lewis acids. They are soluble in all organic solvents, including hexane and toluene, in which they are commercially available as standardized solutions. In general, alkane solvents are preferred since toluene can undergo Friedel-Crafts reactions. On a laboratory scale, these reagents are transferred by syringe like alkyllithiums and, unlike anhydrous solid Lewis acids, they do not require a glove bag or dry box for transfer.

While the Brønsted basicity of the alkyl group is advantageous, these alkyl groups are also nucleophilic. The addition of the alkyl group from the aluminum in the Lewis acid-reagent complex to the electrophilic center can be a serious side reaction. The ease of alkyl donation is R3Al > R2AlCl > R3Al2Cl3 > RAlCl2. When the nucleophilicity of the alkyl group is a problem, a Lewis acid with fewer alkyl groups should be examined. Addition of diethyl ether or another Lewis base may moderate the reaction if its greater acidity causes problems.

Ethylaluminum compounds are more nucleophilic than methylaluminum compounds and can donate a hydrogen as well as an ethyl group to the electrophilic center. Unfortunately, methylaluminum compounds must be prepared from Chloromethane, while ethylaluminum compounds can be prepared much more cheaply from Ethylene. Therefore ethylaluminum compounds are usually used unless the nucleophilicity of the alkyl group is a problem. Although the predominant use of alkylaluminum halides is as Lewis acids, they are occasionally used for the transfer of an alkyl group or hydride to an electrophilic center.

Eq 3 shows an unusual reaction in which the nature of the reaction depends on the amount, acidity, and alkyl group of the alkylaluminum halide.6 Use of 1 equiv of Me2AlCl leads to a concerted ene reaction with the side chains cis. Use of 2 equiv of Me2AlCl produces a more electrophilic aldehyde complex that cyclizes to a zwitterion. Chloride transfer is the major process at -78 °C; at 0 °C, chloride transfer is reversible and a 1,5-proton transfer leads to an ene-type adduct with the side chains trans. Use of 2 equiv of MeAlCl2 forms a cyclic zwitterion that undergoes two 1,2-hydride shifts to form the ketone. A similar zwitterion forms with EtAlCl2, but b-hydride transfer leading to the saturated alcohol is faster than 1,2-hydride shifts.

Catalysis of Diels-Alder Reactions.

EtAlCl2 is a useful Lewis acid catalyst for Diels-Alder reactions. It is reported to be more efficacious for the Diels-Alder reaction of Acrolein and butadiene than either AlCl3 or Et2AlCl.7 It is a useful catalyst for intramolecular Diels-Alder reactions with a,b-unsaturated esters (eq 4)8 and aldehydes9 as dienophiles. It has also proven to be a very efficient catalyst for the inter-10 and intramolecular11 asymmetric Diels-Alder reaction of chiral a,b-unsaturated acyl sultams (eq 5) and has been used to catalyze a wide variety of Diels-Alder reactions.12

Catalysis of Ene Reactions.

Although AlCl3 can be used as a Lewis acid catalyst for ene reactions of a,b-unsaturated esters,13a better results are obtained more reproducibly with EtAlCl2. Ene reactions of Methyl Propiolate proceed in good yield with 1,1-di-, tri-, and tetrasubstituted alkenes (eq 6).14 A precursor to 1,25-dihydroxycholesterol can be prepared by an ene reaction with methyl propiolate. Three equiv of EtAlCl2 are needed since the acetate esters are more basic than methyl propiolate (eq 7).15 Endo products are obtained stereospecifically with methyl a-haloacrylates (eq 8).14 EtAlCl2 has also been used to catalyze intramolecular ene reactions (eq 9).16

EtAlCl2 is usually too strong a Lewis acid for ene reactions of carbonyl compounds.13b,c However, alkenes that contain basic sites that complex to the Lewis acid do not undergo Me2AlCl-catalyzed ene reactions with formaldehyde. In these cases, EtAlCl2 is the preferred catalyst.17,18 The dienyl acetate shown in eq 10 reacts with excess Formaldehyde and EtAlCl2 to provide the conjugated diene ene adduct that undergoes a quasi-intramolecular Diels-Alder reaction to afford a pseudomonic acid precursor. Me2AlCl catalyzes the ene reaction of aliphatic aldehydes with 1,1-di-, tri-, and tetrasubstituted alkenes. Terminal alkenes are less nucleophilic, so the only reaction is addition of a methyl group to the aldehyde. EtAlCl2, a stronger Lewis acid with a less nucleophilic alkyl group, catalyzes the reaction of aliphatic aldehydes with terminal alkenes in CH2Cl2 at 0 °C to give 50-60% of the ene adduct.18 Use of EtAlCl2 as a catalyst affords the best diastereoselectivity in the ene reaction of dibenzylleucinal with Isobutene (eq 11).19 EtAlCl2 has also been used to catalyze intramolecular ene reactions of trifluoromethyl ketones.20

Catalysis of Intramolecular Sakurai Reactions.

EtAlCl2 has been extensively used as a catalyst for intramolecular Sakurai additions. Enones (eqs 12 and 13)21,22 have been most extensively explored. Different products are often obtained with fluoride or Lewis acid catalysis. EtAlCl2 is the Lewis acid used most often although TiCl4 and BF3 have also been used. EtAlCl2 also catalyzes intramolecular Sakurai reactions with ketones23 and other electrophiles.24 The cyclization of electrophilic centers onto alkylstannanes25 and Prins-type additions to vinylsilanes26 are also catalyzed by EtAlCl2.

Catalysis of [2 + 2] Cycloadditions.

EtAlCl2 catalyzes a wide variety of [2 + 2] cycloadditions. These include the addition of alkynes or allenes to alkenes to give cyclobutenes and alkylidenecyclobutanes (eq 14),27 the addition of electron-deficient alkenes to allenyl sulfides (eq 15),28 the addition of propiolate esters to monosubstituted and 1,2-disubstituted alkenes to form cyclobutene carboxylates (eq 16),14b and the addition of allenic esters to alkenes to form cyclobutanes.29

Generation of Electrophilic Cations.

EtAlCl2 has proven to be a useful Lewis acid for inducing a wide variety of electrophilic reactions. It is particularly useful since an excess of the reagent can be used so that all nucleophiles are complexed to acid. Under these conditions, intermediates tend to collapse to give cyclobutanes or undergo hydride shifts to give neutral species. Reaction of the 1:2 Crotonaldehyde-EtAlCl2 complex with 2-methyl-2-butene at -80 °C affords a zwitterion that collapses to give mainly the cyclobutane. Closure of the zwitterion is reversible at 0 °C. Since there are no nucleophiles in solution, two 1,2-hydride shifts take place to give the enal (eq 17).5 Intramolecular versions of these reactions are also quite facile (eqs 18 and 19).5,21 EtAlCl2 promotes the ring enlargement of 1-acylbicyclo[4.2.0]oct-3-enes (eq 20).30

EtAlCl2 catalyzes the Friedel-Crafts acylation of alkenes with acid chlorides,31 the formal [3 + 2] cycloaddition of alkenes with cyclopropane-1,1-dicarboxylates (eq 21),32 the Friedel-Crafts alkylation of anilines and indoles with a-aminoacrylate esters,33 and the formation of allyl sulfoxides from sulfinyl chlorides and alkenes.34 EtAlCl2 induces the Beckmann rearrangement of oxime sulfonates. The cationic intermediates can be trapped with enol silyl ethers (eq 22).35 EtAlCl2 is the preferred catalyst for addition of the cation derived from an a-chloro sulfide to an alkene to give a cation which undergoes a Friedel-Crafts alkylation (eq 23).36

EtAlCl2 reacts with aliphatic sulfones to generate an aluminum sulfinate and a cation that can be reduced to a hydrocarbon by EtAlCl2,37 trapped with a nucleophile such as Allyltrimethylsilane,38 or undergo a pinacol-type rearrangement (eq 24).39

Elimination Reactions.

EtAlCl2 induces elimination of two molecules of HBr from the dibromide to give the dihydropyridine (eq 25).40 The usual base-catalyzed elimination is ineffective.

Nucleophilic Addition.

EtAlCl2 has been used to activate conjugated systems toward attack of an external nucleophile or to transfer a hydride or ethyl group as a nucleophile. Addition of a cuprate to the chiral amide in the presence of EtAlCl2 improves the diastereoselectivity, affording a >93:7 mixture of stereoisomers (eq 26).41 Reaction of butyrolactones with EtAlCl2 reduces the lactone to a carboxylic acid by opening to the cation and hydride delivery (eq 27).42 Sulfonimidyl chlorides react with EtAlCl2 at -78 °C to provide S-ethyl sulfoximines in 65-95% overall yield (eq 28).43

Modification of Carbanions.

Trimethylsilyl allylic carbanions react with aldehydes in the presence of EtAlCl2 exclusively at the a-position to give threo adducts (eq 29).44

Related Reagents.

Diethylaluminum Chloride; Diethylaluminum Iodide; Dimethylaluminum Chloride; Dimethylaluminum Iodide; Methylaluminum Dichloride.


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Barry B. Snider

Brandeis University, Waltham, MA, USA



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