Methylaluminum Bis(2,6-di-t-butylphenoxide)

[128353-30-0]  · C29H45AlO2  · Methylaluminum Bis(2,6-di-t-butylphenoxide)  · (MW 452.72)

(designer Lewis acid for amphiphilic alkylation and conjugate addition)

Solubility: sol CH2Cl2, toluene, hexane.

Form Supplied in: prepared from commercially available reagents and used in situ.

Preparative Method: prepared by reaction of a 1-2 M hexane solution of Trimethylaluminum with 2 equiv of 2,6-di-t-butylphenol in toluene or CH2Cl2 at rt for 1 h in a similar manner to that described in the preparation of MAD or MAT.1

Handling, Storage, and Precautions: the dry solid and solutions are highly flammable and must be handled in the absence of oxygen and moisture. The solution should be used as prepared for best results. Use in a fume hood.

Amphiphilic Alkylation.

The exceptionally bulky, oxygenophilic organoaluminum reagent methylaluminum bis(2,6-di-t-butylphenoxide), like Methylaluminum Bis(2,6-di-t-butyl-4-methylphenoxide) (MAD) and Methylaluminum Bis(2,4,6-tri-t-butylphenoxide) (MAT), has been used for stereoselective activation of carbonyl groups. Combination of this modified organoaluminum compound, as a bulky Lewis acid, with Grignard reagents or organolithium reagents generates the amphiphilic alkylation system, in which substituted cyclohexanones afford equatorial alcohols with high selectivity (eq 1).2 This approach is quite useful in the stereoselective alkylation of steroidal ketones. Thus reaction of cholestan-3-one with Methyllithium gives predominantly 3b-methylcholestan-3a-ol (axial alcohol), whereas the amphiphilic methylation of the ketone gives 3a-methylcholestan-3b-ol (equatorial alcohol) exclusively (eq 2).1,2

The amphiphilic alkylation of a-substituted aldehydes using the title aluminum reagent and Grignard reagents affords anti-alcohols preferentially (eq 3), as also observed with MAD/RMgX or MAT/RMgX.2

Conjugate Addition.

The title reagent has also been used for conjugate alkylation and reduction of a,b-unsaturated ketones with organolithiums and Lithium n-Butyl(diisobutyl)aluminum Hydride, respectively (eqs 4 and 5).3 The 1,4 vs. 1,2 selectivity is not much different from that observed with MAD or MAT.4

1. (a) Maruoka, K.; Itoh, T.; Yamamoto, H. JACS 1985, 107, 4573. (b) Maruoka, K.; Itoh, T.; Sakurai, M.; Nonoshita, K.; Yamamoto, H. JACS 1988, 110, 3588.
2. Itoh, T.; Maruoka, K.; Yamamoto, H., unpublished results.
3. Nonoshita, K.; Maruoka, K.; Yamamoto, H., unpublished results.
4. (a) Maruoka, K.; Nonoshita, K.; Yamamoto, H. TL 1987, 28, 5723. (b) Nonoshita, K.; Maruoka, K.; Yamamoto, H. BCJ 1988, 61, 2241.

Keiji Maruoka & Hisashi Yamamoto

Nagoya University, Japan

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