Aluminum Isopropoxide1


[555-31-7]  · C9H21AlO3  · Aluminum Isopropoxide  · (MW 204.25)

(mild reagent for Meerwein-Ponndorf-Verley reduction;1 Oppenauer oxidation;13 hydrolysis of oximes;16 rearrangement of epoxides to allylic alcohols;17 regio- and chemoselective ring opening of epoxides;20 preparation of ethers21)

Alternate Name: triisopropoxyaluminum.

Physical Data: mp 138-142 °C (99.99+%), 118 °C (98+%); bp 140.5 °C; d 1.035 g cm-3.

Solubility: sol benzene; less sol alcohols.

Form Supplied in: white solid (99.99+% or 98+% purity based on metals analysis).

Preparative Methods: see example below.

Handling, Storage, and Precautions: the dry solid is corrosive, moisture sensitive, flammable, and an irritant. Use in a fume hood.

NMR Analysis of Aluminum Isopropoxide.

Evidence from molecular weight determinations indicating that aluminum isopropoxide aged in benzene solution consists largely of the tetramer (1), whereas freshly distilled molten material is trimeric (2),2 is fully confirmed by NMR spectroscopy.3

Meerwein-Ponndorf-Verley Reduction.

One use of the reagent is for the reduction of carbonyl compounds, particularly of unsaturated aldehydes and ketones, for the reagent attacks only carbonyl compounds. An example is the reduction of crotonaldehyde to crotyl alcohol (eq 1).1 A mixture of 27 g of cleaned Aluminum foil, 300 mL of isopropanol, and 0.5 g of Mercury(II) Chloride is heated to boiling, 2 mL of carbon tetrachloride is added as catalyst, and heating is continued. The mixture turns gray, and vigorous evolution of hydrogen begins. Refluxing is continued until gas evolution has largely subsided (6-12 h). The solution, which is black from the presence of suspended solid, can be concentrated and the aluminum isopropoxide distilled in vacuum (colorless liquid) or used as such. Thus the undistilled solution prepared as described from 1.74 mol of aluminum and 500 mL of isopropanol is treated with 3 mol of crotonaldehyde and 1 L of isopropanol. On reflux at a bath temperature of 110 °C, acetone slowly distills at 60-70 °C. After 8-9 h, when the distillate no longer gives a test for acetone, most of the remaining isopropanol is distilled at reduced pressure and the residue is cooled and hydrolyzed with 6 N sulfuric acid to liberate crotyl alcohol from its aluminum derivative.

The Meerwein-Ponndorf-Verley reduction of the ketone (3) involves formation of a cyclic coordination complex (4) which, by hydrogen transfer, affords the mixed alkoxide (5), hydrolyzed to the alcohol (6) (eq 2).4 Further reflection suggests that under forcing conditions it might be possible to effect repetition of the hydrogen transfer and produce the hydrocarbon (7). Trial indeed shows that reduction of diaryl ketones can be effected efficiently by heating with excess reagent at 250 °C (eq 3).5

A study6 of this reduction of mono- and bicyclic ketones shows that, contrary to commonly held views, the reduction proceeds at a relatively high rate. The reduction of cyclohexanone and of 2-methylcyclohexanone is immeasurably rapid. Even menthone is reduced almost completely in 2 h. The stereochemistry of the reduction of 3-isothujone (8) and of 3-thujone (11) has been examined (eqs 4 and 5). The ketone (8) produces a preponderance of the cis-alcohol (9). The stereoselectivity is less pronounced in the case of 3-thujone (11), although again the cis-alcohol (12) predominates. The preponderance of the cis-alcohols can be increased by decreasing the concentration of ketone and alkoxide.

This reducing agent is the reagent of choice for reduction of enones of type (14) to the a,b-unsaturated alcohols (15) (eq 6). Usual reducing agents favor 1,4-reduction to the saturated alcohol.7

The Meerwein-Ponndorf-Verley reduction of pyrimidin-2(1H)-ones using Zirconium Tetraisopropoxide or aluminum isopropoxide leads to exclusive formation of the 3,4-dihydro isomer (eq 7).8 The former reducing agent is found to be more effective.

Reductions with Chiral Aluminum Alkoxides.

The reduction of cyclohexyl methyl ketone with catalytic amounts of aluminum alkoxide and excess chiral alcohol gives (S)-1-cyclohexylethanol in 22% ee (eq 8).9

Isobornyloxyaluminum dichloride is a good reagent for reducing ketones to alcohols. The reduction is irreversible and subject to marked steric approach control (eq 9).10

Diastereoselective Reductions of Chiral Acetals.

Recently, it has been reported that Pentafluorophenol is an effective accelerator for Meerwein-Ponndorf-Verley reduction.11 Reduction of 4-t-butylcyclohexanone with aluminum isopropoxide (3 equiv) in dichloromethane, for example, is very slow at 0 °C (<5% yield for 5 h), but in the presence of pentafluorophenol (1 equiv), the reduction is cleanly completed within 4 h at 0 °C (eq 10). The question of why this reagent retains sufficient nucleophilicity is still open. It is possible that the o-halo substituents of the phenoxide ligand may coordinate with the aluminum atom, thus increasing the nucleophilicity of the reagent.

Chiral acetals derived from (-)-(2R,4R)-2,4-Pentanediol and ketone are reductively cleaved with high diastereoselectivity by a 1:2 mixture of diethylaluminum fluoride and pentafluorophenol.11 Furthermore, aluminum pentafluorophenoxide is a very powerful Lewis acid catalyst for the present reaction.12 The reductive cleavage in the presence of 5 mol % of Al(OC6F5)3 affords stereoselectively retentive reduced b-alkoxy ketones. The reaction is an intramolecular Meerwein-Ponndorf-Verley reductive and Oppenauer oxidative reaction on an acetal template (eq 11).

The direct formation of a,b-alkoxy ketones is quite useful. Removal of the chiral auxiliary, followed by base-catalyzed b-elimination of the resulting b-alkoxy ketone, easily gives an optically pure alcohol in good yield. Several examples of the reaction are summarized in Table 1.

Although the detailed mechanism is not yet clear, it is assumed that an energetically stable tight ion-paired intermediate is generated by stereoselective coordination of Al(OC6F5)3 to one of the oxygens of the acetal; the hydrogen atom of the alkoxide is then transferred as a hydride from the retentive direction to this departing oxygen, which leads to the (S) configuration at the resulting ether carbon, as described (eq 12).

Oppenauer Oxidation.13

Cholestenone is prepared by oxidation of cholesterol in toluene solution with aluminum isopropoxide as catalyst and cyclohexanone as hydrogen acceptor (eq 13).14

A formate, unlike an acetate, is easily oxidized and gives the same product as the free alcohol.15 For oxidation of (16) to (17) the combination of cyclohexanone and aluminum isopropoxide and a hydrocarbon solvent is used: xylene (bp 140 °C at 760 mmHg) or toluene (bp 111 °C at 760 mmHg) (eq 14).

Hydrolysis of Oximes.16

Oximes can be converted into parent carbonyl compounds by aluminum isopropoxide followed by acid hydrolysis (2N HCl) (eq 15). Yields are generally high in the case of ketones, but are lower for regeneration of aldehydes.

Rearrangement of Epoxides to Allylic Alcohols.

The key step in the synthesis of the sesquiterpene lactone saussurea lactone (21) involved fragmentation of the epoxymesylate (18), obtained from a-santonin by several steps (eq 16).17 When treated with aluminum isopropoxide in boiling toluene (N2, 72 h), (18) is converted mainly into (20). The minor product (19) is the only product when the fragmentation is quenched after 12 h. Other bases such as potassium t-butoxide, LDA, and lithium diethylamide cannot be used. Aluminum isopropoxide is effective probably because aluminum has a marked affinity for oxygen and effects cleavage of the epoxide ring. Meerwein-Ponndorf-Verley reduction is probably involved in one step.

a-Pinene oxide (22) rearranges to pinocarvenol (23) in the presence of 1 mol % of aluminum isopropoxide at 100-120 °C for 1 h.18 The oxide (22) rearranges to pinanone (24) in the presence of 5 mol % of the alkoxide at 140-170 °C for 2 h. Aluminum isopropoxide has been used to rearrange (23) to (24) (200 °C, 3 h, 80% yield) (eq 17).19

Regio- and Chemoselective Ring Opening of Epoxides.

Functionalized epoxides are regioselectively opened using trimethylsilyl azide/aluminum isopropoxide, giving 2-trimethylsiloxy azides by attack on the less substituted carbon (eq 18).20

Preparation of Ethers.

Ethers ROR are prepared from aluminum alkoxides, Al(OR)3, and alkyl halides, RX. Thus EtCHMeOH is treated with Al, HgBr2, and MeI in DMF to give EtCHMeOMe (eq 19).21

1. Wilds, A. L. OR 1944, 2, 178.
2. Shiner, V. J.; Whittaker, D.; Fernandez, V. P. JACS 1963, 85, 2318.
3. Worrall, I. J. J. Chem. Educ. 1969, 46, 510.
4. Woodward, R. B.; Wendler, N. L.; Brutschy, F. J. JACS 1945, 67, 1425.
5. Hoffsommer, R. D.; Taub, D.; Wendler, N. L. CI(L) 1964, 482.
6. Hach, V. JOC 1973, 38, 293.
7. Picker, D. H.; Andersen, N. H.; Leovey, E. M. K. SC 1975, 5, 451.
8. Høseggen, T.; Rise, F.; Undheim, K. JCS(P1) 1986, 849.
9. Doering, W. von E.; Young, R. W. JACS 1950, 72, 631.
10. Nasipuri, D.; Sarker, G. JIC 1967, 44, 165.
11. Ishihara, K.; Hanaki, N.; Yamamoto, H. JACS 1991, 113, 7074.
12. Ishihara, K.; Hanaki, N.; Yamamoto, H. SL 1993, 127; JACS, 1993, 115, 10 695.
13. Djerassi, C. OR 1951, 6, 207.
14. Eastham, J. F.; Teranishi, R. OSC 1963, 4, 192.
15. Ringold, H. J.; Löken, B.; Rosenkranz, G.; Sondheimer, F. JACS 1956, 78, 816.
16. Sugden, J. K. CI(L) 1972, 680.
17. Ando, M.; Tajima, K.; Takase, K. CL 1978, 617.
18. Scheidl, F. S 1982, 728.
19. Schmidt, H. CB 1929, 62, 104.
20. Emziane, M.; Lhoste, P.; Sinou, D. S 1988, 541.
21. Lompa-Krzymien, L.; Leitch, L. C. Pol. J. Chem. 1983, 57, 629.

Kazuaki Ishihara & Hisashi Yamamoto

Nagoya University, Japan

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