Diisobutylaluminum Hydride1


[1191-15-7]  · C8H19Al  · Diisobutylaluminum Hydride  · (MW 142.22)

(reducing agent for many functional groups; opens epoxides; hydroaluminates alkynes and alkenes)

Alternate Names: DIBAL; DIBAL-H; DIBAH.

Physical Data: mp -80 to -70 °C; bp 116-118 °C/1 mmHg; d 0.798 g cm-3; fp -18 °C.

Solubility: sol pentane, hexane, heptane, cyclohexane, benzene, toluene, xylenes, ether, dichloromethane, THF.

Form Supplied in: can be purchased as a neat liquid or as 1.0 and 1.5 M solutions in cyclohexane, CH2Cl2, heptane, hexanes, THF, and toluene.

Handling, Storage, and Precautions: neat liquid is pyrophoric; solutions react very vigorously with air and with H2O, and related compounds, giving rise to fire hazards; use in a fume hood, in the absence of oxygen and moisture (see Lithium Aluminum Hydride for additional precautions); THF solutions should only be used below 70 °C, as above that temperature ether cleavage is problematic.

Reduction of Functional Groups.2

Diisobutylaluminum hydride has several acronyms: DIBAH, DIBAL-H, and DIBAL. For the purpose of this article, DIBAL will be used.

In general, aldehydes, ketones, acids, esters, and acid chlorides are all reduced to the corresponding alcohols by this reagent. Alkyl halides are unreactive towards DIBAL. Amides are reduced to amines, while nitriles afford aldehydes upon hydrolysis of an intermediate imine. Isocyanates are also reduced to the corresponding imines. Nitro compounds are reduced to hydroxylamines. Disulfides are reduced to thiols, while sulfides, sulfones, and sulfonic acids are unreactive in toluene at 0 °C. Tosylates are converted quantitatively to the corresponding alkanes. Cyclic imides can be reduced to carbinol lactams.

Comparable stereochemistry2 is observed in the reduction of ketones with DIBAL, Aluminum Hydride, and Lithium Aluminum Hydride. Excellent 1,3-asymmetric induction is possible with DIBAL (eq 1); however, this is strongly solvent dependent.3a

In addition to the hydroxy directing group, amines and amides also showed excellent 1,3-asymmetric induction.3b In conjunction with chiral additives, DIBAL can reduce ketones with moderate to good enantioselectivity (eq 2).4 The use of the Lewis acid Methylaluminum Bis(2,6-di-t-butyl-4-methylphenoxide) (MAD) along with DIBAL allows discrimination between carbonyl groups (eq 3).5,6

Reduction of a-halo ketones to the carbonyl compounds can be accomplished with DIBAL in the presence of Tin(II) Chloride and N,N,N,N-Tetramethylethylenediamine (eqs 4 and 5).7 Under these conditions, vicinal dibromides are converted to the corresponding alkenes.

DIBAL is the reagent of choice (see also Aluminum Hydride) for the reduction of a,b-unsaturated ketones to the corresponding allylic alcohols (eq 6).8a A reagent derived from DIBAL and Methylcopper in HMPA alters the regiochemistry such that 1,4-reduction results (eq 7).8b Reductions of chiral b-keto sulfoxides occur with high diastereoselectivity.9 The choice of reduction conditions makes it possible to obtain both epimers at the carbinol carbon (eqs 8 and 9).

In conjuction with Triethylaluminum, DIBAL has been used to mediate a reductive pinacol rearrangement10 with enantiocontrol, as shown in eq 10.22

DIBAL is an excellent reagent for the reduction of a,b-unsaturated esters to allylic alcohols without complications from 1,4-addition (eq 11).11

Due to its Lewis acidity, DIBAL can be used in the reductive cleavage of acetals (see also Aluminum Hydride). Chiral acetates are reduced with enantioselectivity (eq 12).12 Oxidation of the intermediate alcohol followed by b-elimination gives an optically active alcohol, resulting in a net enantioselective reduction of the corresponding ketone.

At low temperatures DIBAL converts esters to the corresponding aldehydes (eq 13)13 and lactones to lactols (eq 14).14 DIBAL reduction of a,b-unsaturated g-lactones followed by an acidic work-up transforms the intermediate lactol to the furan (eq 15).15 The reduction of nitriles can lead to aldehydes after hydrolysis of an intermediate imine (eq 16).16 However, cyclic imines can be produced if a Sodium Fluoride work-up follows the reduction of halonitriles (eq 17).17 Furthermore, imines can be reduced with excellent stereocontrol (eq 18).18

DIBAL can also be used for the reductive cleavage of cyclic aminals and amidines (eq 19).19 Oximes can be reduced to amines. Due to the Lewis acidity of DIBAL, however, rearranged products are obtained (eq 20).20 This chemistry was used to prepare the alkaloid pumiliotoxin C via the Beckmann rearrangement/alkylation sequence shown in eq 21.21

While sulfones are unreactive with DIBAL at 0 °C in toluene,2 reduction to the corresponding sulfide has been accomplished at higher temperatures.22 This reaction can be accomplished with Lithium Aluminum Hydride, but fewer equivalents are required and yields are better using DIBAL (eq 22).

The reagent combination of DIBAL and n-Butyllithium, which is most likely lithium diisobutylbutylaluminum hydride, has also been used as a reducing agent.23

Epoxide Ring Opening.

As a result of its Lewis acidity, several reaction pathways are followed in the reductive ring opening of epoxides by DIBAL. Attack at the more hindered carbon via carbenium ion-like intermediates (see also Aluminum Hydride) or SN2 type reactions, are both known with vinyl epoxides. These modes stand in contrast to results with LiAlH4 (eqs 23-25).24

Hydroalumination Reactions.

DIBAL reacts with alkynes and alkenes to give hydroalumination products. Syn additions are usually observed; however, under appropriate conditions, equilibration to give a net anti addition is possible.25 If the substrate has both an alkene and an alkyne group, then chemoselectivity for the alkyne is observed (eq 26).26

The intermediate alkenylalane can be used in several ways. If a protiolytic work-up is used, then formation of the corresponding (Z)-alkene is observed (eq 27).27 Treatment of the alkenylalane with Methyllithium affords an ate complex which is nucleophilic and reacts with a variety of electrophiles, e.g. alkyl halides, CO2, MeI, epoxides, tosylates, aldehydes, and ketones (eq 28).1c,1h,26

Hydroalumination of a terminal alkene followed by treatment of the intermediate alane with oxygen gives a primary alcohol (eq 29).28

Alkenylalanes can dimerize to afford 1,3-butadienes (eq 30),29 and can be cyclopropanated under Simmons-Smith conditions to give cyclopropylalanes (eq 31),30 which can be used for further chemistry.

Alkenylalanes can also be transmetalated (eq 32),31 or coupled with vinyl halides via palladium catalysis (eq 33).32

Addition of DIBAL to allenes has been observed to occur at the more highly substituted double bond (eq 34).33

The conversion of unconjugated enynes to cyclic compounds has also been accomplished using DIBAL (eq 35).34

Related hydroalumination reactions have been reported using Lithium Aluminum Hydride.

1. (a) Mole, T.; Jeffery, E. A. Organoaluminum Compounds; Elsevier: Amsterdam, 1972. (b) Winterfeldt, W. S 1975, 617. (c) Zweifel, G.; Miller, J. A. OR 1984, 32, 375. (d) Maruoka, K; Yamamoto, H. AG(E) 1985, 24, 668. (e) Maruoka, K.; Yamamoto, H. T 1988, 44, 5001. (f) Dzhemilev, V. M.; Vostrikova, O. S.; Tolstikov, G. A. RCR 1990, 59, 1157. (g) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis; VCH: New York, 1991. (h) Eisch, J. J. COS 1991, 8, 733. (i) Eisch, J. J. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed.; Pergamon: Oxford, 1982; vol. 1, p 555. (j) Zietz, J. R.; Robinson, G. C.; Lindsay, K. L. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed.; Pergamon: Oxford, 1982; vol. 7, p 365.
2. Yoon, N. M.; Gyoung, Y. S. JOC 1985, 50, 2443.
3. (a) Kiyooka, S.; Kuroda, H.; Shimasaki, Y. TL 1986, 27, 3009. (b) Barluenga, J.; Aguilar, E.; Fustero, S.; Olano, B.; Viado, A. L. JOC 1992, 57, 1219.
4. Oriyama, T.; Mukaiyama, T. CL 1984, 2071
5. (a) Maruoka, K.; Itoh, T.; Yamamoto, H. JACS 1985, 107, 4573. (b) Maruoka, K.; Sakurai, M.; Yamamoto, H. TL 1985, 26, 3853
6. Maruoka, K.; Araki, Y.; Yamamoto, H. JACS 1988, 110, 2650.
7. Oriyama, T.; Mukaiyama, T. CL 1984, 2069.
8. (a) Wilson, K. E.; Seidner, R. T.; Masamune, S. CC 1970, 213. (b) Tsuda, T.; Kawamoto, T.; Kumamoto, Y.; Saegusa, T. SC 1986, 16, 639.
9. Solladie, G.; Frechou, G.; Demailly, G. TL 1986, 27, 2867.
10. Suzuki, K.; Katayama, E.; Matsumoto, T.; Tsuchihashi, G. TL 1984, 25, 3715.
11. Daniewski, A. R.; Wojceichowska, W. JOC 1982, 47, 2993.
12. Mori, A.; Fujiwara, J.; Maruoka, K.; Yamamoto, H. TL 1983, 24, 4581.
13. Szantay, C.; Toke, L.; Kolonits, P. JOC 1966, 31, 1447.
14. Vidari, G.; Ferrino, S.; Grieco, P. A. JACS 1984, 106, 3539.
15. Kido, F.; Noda, Y.; Maruyama, T.; Kabuto, C.; Yoshikoshi, A. JOC 1981, 46, 4264.
16. Marshall, J. A.; Andersen, N. H.; Schlicher, J. W. JOC 1970, 35, 858.
17. Overman, L. E.; Burk, R. M. TL 1984, 25, 5737.
18. Matsumura, Y.; Maruoka, K.; Yamamoto, H. TL 1982, 23, 1929.
19. Yamamoto, H.; Maruoka, K. JACS 1981, 103, 4186.
20. Sasatani, S.; Miyazaki, T.; Maruoka, K.; Yamamoto, H. TL 1983, 24, 4711.
21. Hattori, K.; Matsumura, Y.; Miyazaki, T.; Maruoka, K.; Yamamoto, H. JACS 1981, 103, 7368.
22. Gardner, J. N.; Kaiser, S.; Krubiner, A. Lucas, H. CJC 1973, 51, 1419.
23. Kim., S.; Ahn, K. H. JOC 1984, 49, 1717.
24. Lenox, R. S.; Katzenellenbogen, J. A. JACS 1973, 95, 957.
25. Eisch, J. J.; Foxton, M. W. JOC 1971, 36, 3520.
26. Utimoto, K.; Uchida, K.; Yamaya, M.; Nozaki, H. TL 1977, 3641.
27. Gensler, W. J.; Bruno, J. J. JOC 1963, 28, 1254.
28. Ziegler, K.; Kropp, F.; Zosel, K. LA 1960, 629, 241.
29. Eisch, J. J.; Kaska, W. C. JACS 1966, 88, 2213.
30. Zweifel, G.; Clark, G. M.; Whitney, C. C. JACS 1971, 93, 1305.
31. (a) Negishi, E.; Boardman, L. D. TL 1982, 23, 3327. (b) Negishi, E.; Jadhav, K. P.; Daotien, N. TL 1982, 23, 2085.
32. Babas, S.; Negishi, E. JACS 1976, 98, 6729.
33. Monturi, M.; Gore, J. TL 1980, 21, 51.
34. Zweifel, G.; Clark, G. M.; Lynd, R. CC 1971, 1593.

Paul Galatsis

University of Guelph, Ontario, Canada

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