Dimethylaluminum Chloride1

Me2AlCl

[1184-58-3]  · C2H6AlCl  · Dimethylaluminum Chloride  · (MW 92.51)

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

Alternate Name: chlorodimethylaluminum.

Physical Data: mp -21 °C; bp 126-127 °C; d 0.996 g cm-3.

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

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

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

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

Introduction.

The general properties of alkylaluminum halides as Lewis acids are discussed in the entry for Ethylaluminum Dichloride. Dialkylaluminum halides are less acidic than alkylaluminum dihalides. Me2AlCl is more expensive than Diethylaluminum Chloride, but the methyl group of Me2AlCl is much less nucleophilic than the ethyl group of Et2AlCl. Much higher yields will generally be obtained by use of Me2AlCl in the ene reactions of carbonyl compounds. In other cases, such as the Diels-Alder reactions of a,b-unsaturated esters, comparable yields will be obtained with either Lewis acid.

Catalysis of Diels-Alder Reactions.

Me2AlCl has been used as a Lewis acid catalyst for inter- and intramolecular Diels-Alder reactions with a wide variety of dienophiles. High diastereoselectivity is obtained from chiral a,b-unsaturated N-acyloxazolidinones with more than 1 equiv of Me2AlCl.2 Use of Me2AlCl as a catalyst affords high yields in inter- and intramolecular Diels-Alder reactions of a,b-unsaturated ketones (eq 1),3,4 and intramolecular Diels-Alder reactions of a,b-unsaturated aldehydes.4,5 Me2AlCl-catalyzed Diels-Alder reactions of a,b-unsaturated N-acylsultams (eq 2)6 and 1-mesityl-2,2,2-trifluoroethyl acrylate (eq 3)7 proceed in high yield with excellent asymmetric induction. Methylaluminum sesquichloride, prepared from Me2AlCl and Methylaluminum Dichloride, catalyzes an intramolecular Diels-Alder reaction with an aldehyde as the dienophile to afford a dihydropyran.8

Catalysis of Ene Reactions.9

A wide variety of Lewis acids will catalyze the ene reactions of formaldehyde with electron-rich alkenes. Electron-deficient aldehydes, such as chloral and glyoxylate esters, also undergo ene reactions with a variety of Lewis acid catalysts. Ene reactions of aliphatic and aromatic aldehydes with alkenes that can form a tertiary cation, and of formaldehyde with mono- and 1,2-disubstituted alkenes, are best carried out with 1 or more equiv of Me2AlCl. The alcohol-Me2AlCl complex produced in the ene reaction decomposes rapidly to give methane and a nonbasic aluminum alkoxide that does not react further (eq 4). This prevents solvolysis of the alcohol-Lewis acid complex or protonation of double bonds. Good to excellent yields of ene adducts are obtained from aliphatic and aromatic aldehydes and 1,1-di- and trisubstituted alkenes. Formaldehyde is more versatile and gives good yields of ene adducts with all classes of alkenes.10 When less than 1 equiv of Me2AlCl is used, g-chloro alcohols are formed, resulting from the stereospecifically cis addition of the hydroxymethyl and chloride groups to the double bond (eq 5). The chloro alcohols are converted to ene-type adducts in the presence of excess Me2AlCl. Formaldehyde undergoes Me2AlCl-induced reactions with terminal alkynes to give a 2:3 mixture of the ene adduct allenic alcohol and the (Z)-3-chloro allylic alcohol in 50-75% yield (eq 6).11

Me2AlCl catalyzes the ene reactions of a variety of aldehydes with (Z)-3b-acetoxy-5,17(20)-pregnadiene at -78 °C.12 The stereoselectivity with aliphatic aldehydes is >10:1 in favor of the 22a-isomer, while aromatic aldehydes produce predominantly the 22b-isomer (eq 7). Me2AlCl is also the Lewis acid of choice for ene reactions of a-halo aldehydes (eq 8).13 Ene reactions of vinyl sulfides to produce enol silyl ethers are also catalyzed by Me2AlCl (eq 9).14

Type-I intramolecular ene reactions of aldehydes, such as citronellal, that contain electron-rich trisubstituted double bonds proceed readily thermally or with a variety of Lewis acids. Intramolecular ene reactions with less nucleophilic 1,2-disubstituted double bonds proceed efficiently with Me2AlCl as the Lewis acid catalyst (eqs 10 and 11).15,16

Type-II intramolecular ene reactions of aldehydes and ketones proceed readily with Me2AlCl as the Lewis acid.17-19 Unsaturated aldehydes and ketones can be generated in situ by Me2AlCl-catalyzed reaction of Acrolein and Methyl Vinyl Ketone with alkylidenecycloalkanes at low temperatures (eq 12).17 The monocyclic aldehyde reacts further under these conditions. The monocyclic ketone can be isolated at low temperature but undergoes a second ene reaction at rt to give the bicyclic alcohol. b-Keto esters form tertiary alcohols in intramolecular ene reactions. The products are stable because they are converted to the aluminum alkoxide (eq 13).18 Intramolecular Me2AlCl-catalyzed ene reactions have been used for the preparation of the bicyclic mevinolin ring system (eq 14).19

Generation of Electrophilic Cations.

Me2AlCl in dichloromethane cleaves THP ethers without deprotecting t-butyldimethylsilyl ethers.20 Azido enol silyl ethers undergo Me2AlCl-catalyzed reactions with Allyltributylstannane and enol ethers, giving conjugate addition-type products that are isolated as the silyl enol ethers (eq 15).21 Me2AlCl will open norbornane epoxide to the rearranged chlorohydrin.22

Formation and Reaction of Aluminum Enolates.

Aluminum enolates prepared from esters react with imines to give a b-lactam resulting from aldol-type addition followed by ring closure (eq 16).23

Formation and Reaction of Alkynylaluminum Reagents.

Lithium acetylides react with Me2AlCl to give dimethylaluminum acetylides that react analogously to the more commonly used diethylaluminum acetylides (see Diethylaluminum Ethoxyacetylide). Addition of the aluminum acetylide to propiolactone results in an SN2 reaction to give an alkynic acid (eq 17).24

Reaction as a Nucleophile.

Me2AlCl will react analogously to MeMgBr and transfer a methyl group to many nucleophiles. Since Methylmagnesium Bromide and Methyllithium are readily available, use of Me2AlCl to deliver a methyl group is needed only when the stereochemistry of addition is an important issue. High levels of asymmetric induction are obtained in the conjugate addition of Me2AlCl to unsaturated acyloxazolidinones with carbohydrate-derived chiral auxiliaries (eq 18).25 Me2AlCl differs from higher dialkylaluminum chlorides in that methyl addition is a radical process that requires photochemical or radical initiation. Me2AlCl will convert acid chlorides to methyl ketones.26


1. For reviews, see Ref. 1 under Ethylaluminum Dichloride.
2. (a) Evans, D. A.; Chapman, K. T.; Bisaha, J. TL 1984, 25, 4071. (b) Evans, D. A.; Chapman, K. T.; Bisaha, J. JACS 1984, 106, 4261. (c) Evans, D. A.; Chapman, K. T.; Bisaha, J. JACS 1988, 110, 1238. (d) Sugahara, T.; Iwata, T.; Yamaoka, M.; Takano, S. TL 1989, 30, 1821. (e) Hauser, F. M.; Tommasi, R. A. JOC 1991, 56, 5758.
3. (a) Sakan, K.; Smith, D. A. TL 1984, 25, 2081. (b) Ireland, R. E.; Dow, W. C.; Godfrey, J. D.; Thaisrivongs, S. JOC 1984, 49, 1001.
4. Marshall, J. A.; Shearer, B. G.; Crooks, S. L. JOC 1987, 52, 1236.
5. Takeda, K.; Kobayashi, T.; Saito, K.; Yoshii, E. JOC 1988, 53, 1092.
6. Oppolzer, W.; Dupuis, D.; Poli, G.; Raynham, T. M.; Bernardinelli, G. TL 1988, 29, 5885.
7. Corey, E. J.; Cheng, X.-M.; Cimprich, K. A. TL 1991, 32, 6839.
8. Trost, B. M.; Lautens, M.; Hung, M. H.; Carmichael, C. S. JACS 1984, 106, 7641.
9. (a) Snider, B. B. COS 1991, 5, 1. (b) Snider, B. B. COS 1991, 2, 527. (c) Mikami, K.; Shimizu, M. CRV 1992, 92, 1021.
10. (a) Snider, B. B.; Rodini, D. J.; Kirk, T. C.; Cordova, R. JACS 1982, 104, 555. (b) Cartaya-Marin, C. P.; Jackson, A. C.; Snider, B. B. JOC 1984, 49, 2443. (c) Tietze, L. F.; Beifuss, U.; Antel, J.; Sheldrick, G. M. AG(E) 1988, 27, 703. (d) Metzger, J. O.; Biermann, U. S 1992, 463.
11. Rodini, D. J.; Snider, B. B. TL 1980, 21, 3857.
12. (a) Mikami, K.; Loh, T.-P.; Nakai, T. TL 1988, 29, 6305. (b) Mikami, K.; Loh, T.-P.; Nakai, T. CC 1988, 1430. (c) Houston, T. A.; Tanaka, Y.; Koreda, M. JOC 1993, 58, 4287.
13. Mikami, K.; Loh, T.-P.; Nakai, T. CC 1991, 77.
14. Tanino, K.; Shoda, H.; Nakamura, T.; Kuwajima, I. TL 1992, 33, 1337.
15. Snider, B. B.; Karras, M.; Price, R. T.; Rodini, D. J. JOC 1982, 47, 4538.
16. (a) Smith, A. B., III; Fukui, M. JACS 1987, 109, 1269. (b) Smith, A. B., III; Fukui, M.; Vaccaro, H. A.; Empfield, J. R. JACS 1991, 113, 2071.
17. (a) Snider, B. B.; Deutsch, E. A. JOC 1982, 47, 745. (b) Snider, B. B.; Deutsch, E. A. JOC 1983, 48, 1822. (c) Snider, B. B.; Goldman, B. E. T 1986, 42, 2951.
18. Jackson, A. C.; Goldman, B. E.; Snider, B. B. JOC 1984, 49, 3988.
19. (a) Wovkulich, P. M.; Tang, P. C.; Chadha, N. K.; Batcho, A. D.; Barrish, J. C.; Uskoković, M. R. JACS 1989, 111, 2596. (b) Barrish, J. C.; Wovkulich, P. M.; Tang, P. C.; Batcho, A. D.; Uskoković, M. R. TL 1990, 31, 2235. (c) Quinkert, G.; Schmalz, H.-G.; Walzer, E.; Kowalczyk-Przewloka, T.; Dürner, G.; Bats, J. W. AG(E) 1987, 26, 61. (d) Quinkert, G.; Schmalz, H.-G.; Walzer, E.; Gross, S.; Kowalczyk-Przewloka, T.; Schierloh, C.; Dürner, G.; Bats, J. W.; Kessler, H. LA 1988, 283. (e) Cohen, T.; Guo, B.-S. T 1986, 42, 2803.
20. Ogawa, Y.; Shibasaki, M. TL 1984, 25, 663.
21. Magnus, P.; Lacour, J. JACS 1992, 114, 3993.
22. Murray, T. F.; Varma, V.; Norton, J. R. JOC 1978, 43, 353.
23. Wada, M.; Aiura, H.; Akiba, K.-Y. TL 1987, 28, 3377.
24. Shinoda, M.; Iseki, K.; Oguri, T.; Hayasi, Y.; Yamada, S.-I.; Shibasaki, M. TL 1986, 27, 87.
25. (a) Rück, K.; Kunz, H. AG(E) 1991, 30, 694. (b) SL 1992, 343. (c) S 1993, 1018.
26. Ishibashi, H.; Takamuro, I.; Mizukami, Y.-I.; Irie, M.; Ikeda, M. SC 1989, 19, 443.

Barry B. Snider

Brandeis University, Waltham, MA, USA



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