[13497-97-7]  · AlCl2H  · Dichloroalane  · (MW 98.90)

(reduction of acetals,1 orthoesters,2 oxazolidines,3 and ozonides;4 hydrogenolysis of ethers,5 and alcohols;6 ring opening of epoxides7 and oxetanes;8 reduction of ketones,9 azetidinones,10 and phosphonates;11 hydroalumination of alkenes12)

Physical Data: bp 95 °C in high vacuum.13a

Solubility: sol benzene, chloroform, ether, THF.

Form Supplied in: not commercially available.

Analysis of Reagent Purity: normally prepared in situ as a solution in ether and used without purification or analysis; however, the bis-THF adduct has been characterized by NMR, IR, and elemental analysis.13b

Preparative Methods: generally prepared in situ from Lithium Aluminum Hydride (1 equiv) and Aluminum Chloride (3 equiv) in ether at 0 °C;4,11b alternatively, can be prepared in pure form by reaction of AlH3 (1 equiv) with AlCl3 (2 equiv) in ether followed by vacuum distillation.13a The bis-THF adduct [Cl2AlH.2(THF)] is a stable crystalline compound (mp 90-95 °C) which can be prepared by either of the methods described above (substituting THF for ether as the solvent).13b

Purification: by distillation.

Handling, Storage, and Precautions: generally prepared in situ and used immediately; handle under dry nitrogen in a fume hood.

Reduction of Acetals, Orthoesters, and Oxazolidines.

Dichloroalane (1) may be used for the reduction of acetals to ethers.1 However, Dibromoalane is generally superior for this purpose. For the reduction of orthoesters to acetals, either (1) or alane (AlH3) is suitable (eq 1).2 Similarly, oxazolidines may be reduced to amino alcohols with either (1) or alane.3 Substitution of alane for (1) may result in a different stereochemical outcome in some cases.2,3

Reduction of Ozonides to Ethers.

Ozonides can be reduced to ethers with (1) in low to moderate yields (varying amounts of diol are obtained as the major byproduct) (eq 2).4 Substitution of Sodium Borohydride-Trifluoroacetic Acid for (1) in this reaction results in considerable differences in product ratios and yields.

Hydrogenolysis of Fluorenyl Ethers and Benzylic/Allylic Alcohols.

Dichloroalane (1) reductively cleaves fluoren-9-yl ethers in refluxing dichloromethane/ether (eq 3).5 The necessity of elevated temperatures may lead to formation of byproducts in some cases. Benzylic alcohols (and some chlorides) can also be cleaved by reaction with (1), although the necessary conditions are again relatively harsh and byproduct formation is common.6a Catalytic hydrogenolysis (H2, Palladium on Carbon) is probably superior for most substrates. Limited examples of hydrogenolysis of allylic alcohols with (1) also exist.6b

Ring Opening of Epoxides and Oxetanes.

Dichloroalane (1) has been used to reduce epoxides, although rearrangement and/or byproduct formation is common due to the Lewis acidity of the reagent.7 For example, attempted reduction of an alkene-substituted cyclohexane epoxide afforded predominantly cyclized products with no reduced product present (eq 4).7a The best reduction substrates are phenyl-substituted epoxides with limited rearrangement options.7c Similar results have been reported for reduction of oxetanes with (1).8

Reduction of Ketones.

In combination with Copper(I) Iodide, (1) can effect 1,4-reduction of a,b-unsaturated ketones. However, lithium aluminum hydride/copper iodide is generally superior for this purpose.9a There are several examples of the reduction of ketones with (1).9b,c,d However, (1) has no apparent advantage over more readily accessible hydride reagents (e.g. sodium borohydride or lithium aluminum hydride) for this purpose. Dibromoalane is superior to (1) for selective reduction of the more hindered of two ketones.9e

Reduction of Azetidinones to Azetidines.

Azetidin-2-ones can be efficiently reduced with (1) in refluxing ether to afford azetidines in excellent yield (eq 5).10 This reagent is markedly superior to other reducing agents for this purpose.

Reduction of Phosphonates to Phosphines.

Dichloroalane (1) is an excellent reagent for the preparation of alkynylphosphines,11a allenylphosphines,11a or vinylphosphines11b by reduction of the corresponding phosphonates. For example, vinylphosphine has been prepared on a gram scale by reduction of a vinylphosphonate with (1) (eq 6).11b Attempts to effect this reduction with lithium aluminum hydride or alane were unsuccessful.

Hydroalumination of Alkenes.

Alkylaluminum species derived by reaction of (1) with alkenes can react with a variety of electrophiles. The net result of this process is the addition of HX across the double bond in an anti-Markovnikov sense. The reaction may be catalyzed by an organoborane12a or a transition metal hydride.12b For example, organoborane-catalyzed hydroalumination of 1-dodecene with (1) followed by reaction of the intermediate organoaluminum species with Bromine affords 1-bromododecane in excellent yield (eq 7).12a

Bis(dialkylamino)alanes are also excellent reagents for this purpose and may be superior to (1).12b It is possible to obtain alcohols via hydroalumination-oxidation of alkenes,12c but hydroboration-oxidation is preferred for this transformation. It has also been reported that propargylic ethers and amines can be reduced to the corresponding trans allylic ethers and amines by the action of (1).12f However, (1) appears to be inferior to other hydride reagents for this purpose.

Related Reagents.

Aluminum Hydride; Dibromoalane; Lithium Aluminum Hydride-Copper(I) Iodide.

1. (a) Mori, A.; Fujiwara, J.; Maruoka, K.; Yamamoto, H. TL 1983, 24, 4581. (b) Mori, A.; Fujiwara, J.; Maruoka, K.; Yamamoto, H. JOM 1985, 285, 83. (c) Zajac, W. W., Jr.; Byrne, K. J. JOC 1972, 37, 521. (d) Loewen, P. C.; Makhubu, L. P.; Brown, R. K. CJC 1972, 50, 1502.
2. Eliel, E. L.; Nader, F. W. JACS 1970, 92, 3045.
3. Fuganti, C.; Ghiringhelli, D.; Grasselli, P.; Mazza, M. TL 1974, 2261.
4. Fujisaka, T.; Nojima, M.; Kusabayashi, S. JOC 1985, 50, 275.
5. Hajko, J.; Borbas, A.; Liptak, A.; Kajtar-Peredy, M. Carbohydr. Res. 1991, 216, 413.
6. (a) Brewster, J. H.; Bayer, H. O.; Osman, S. F. JOC 1964, 29, 110. (b) Brewster, J. H.; Bayer, H. O. JOC 1964, 29, 105.
7. (a) Maruoka, K.; Saito, S.; Ooi, T.; Yamamoto, H. SL 1991, 255. (b) Elsenbaumer, R. L.; Mosher, H. S.; Morrison, J. D.; Tomaszewski, J. E. JOC 1981, 46, 4034. (c) Guyon, R.; Villa, P. BSF(2) 1975, 2599 (CA 1976, 84, 163 877q).
8. Schaal, D.; Seyden-Penne, J. CR(C) 1968, 266, 217 (CA 1968, 68, 68 558x).
9. (a) Ashby, E. C.; Lin, J. J.; Kovar, R. JOC 1976, 41, 1939. (b) Guyon, R.; Villa, P. BSF(2) 1977, 152 (CA 1977, 87, 84 195z). (c) Guyon, R.; Villa, P. BSF(2) 1977, 145 (CA 1977, 87, 84 194y). (d) Pauling, H. HCA 1975, 58, 1781 (CA 1976, 84, 44 375q). (e) Maruoka, K.; Araki, Y.; Yamamoto, H. JACS 1988, 110, 2650.
10. Yamashita, M.; Ojima, I. JACS 1983, 105, 6339.
11. (a) Guillemin, J. C.; Savignac, P.; Denis, J. M. IC 1991, 30, 2170. (b) Cabioch, J. L.; Denis, J. M. JOM 1989, 377, 227.
12. (a) Maruoka, K.; Sano, H.; Shinoda, K.; Nakai, S.; Yamamoto, H. JACS 1986, 108, 6036. (b) Ashby, E. C.; Noding, S. A. JOC 1979, 44, 4364. (c) Maruoka, K.; Sano, H.; Shinoda, K.; Yamamoto, H. CL 1987, 73. (d) Sansoulet, J.; Welvart, Z. BSF(2) 1962, 77 (CA 1963, 58, 5626e). (e) Sato, F.; Sato, S.; Kodama, H.; Sato, M. JOM 1977, 142, 71. (f) Kruglikova, R. I.; Babaeva, L. G.; Polteva, N. A.; Unkovskii, B. V. JOU 1974, 10, 968.
13. (a) Wiberg, E.; Schmidt, M. ZN(B) 1951, 6, 460. (b) Schmidt, D. L.; Flagg, E. E. IC 1967, 6, 1262.

Timothy A. Blizzard

Merck Research Laboratories, Rahway, NJ, USA

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