Methylaluminum Bis(4-bromo-2,6-di-t-butylphenoxide)

[118495-99-1]  · C29H43AlBr2O2  · Methylaluminum Bis(4-bromo-2,6-di-t-butylphenoxide)  · (MW 610.50)

(designer Lewis acid for Claisen rearrangements;1-4 epoxide rearrangements;5-7 intramolecular ene reactions;8-10 a-primary alkylation of ketones;11 oxetanone synthesis12)

Alternate Name: MABR.

Solubility: sol toluene, CH2Cl2.

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 4-bromo-2,6-di-t-butylphenol (2 equiv) in CH2Cl2 or toluene at 25 °C for 1 h.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.

Claisen Rearrangement.

The modified organoaluminum reagent methylaluminum bis(4-bromo-2,6-di-t-butylphenoxide) was developed as a bulky Lewis acid for effecting the stereoselective Claisen rearrangement of allylic vinyl ethers.1 Thus reaction of 1-isobutyl-2-propenyl vinyl ether with MABR in CH2Cl2 at -78 °C affords (Z)-7-methyl-4-octenal with high stereoselectivity (E/Z = 7:93). This selectivity is opposite to that observed in ordinary thermal and Lewis acid-induced rearrangements (eq 1). The Claisen rearrangement of the optically active substrate with MABR reveals a chairlike transition-state conformation with the isobutyl substituent axial in order to relieve a severe 1,2-steric interaction between the isobutyl and very bulky MABR ligands.2

Such unusual behavior is also observed in the MABR-promoted Claisen rearrangement of bisallylic vinyl ethers and allylic phenyl ethers (eq 2).3,4

Epoxide Rearrangements.

A new, stereocontrolled rearrangement of epoxy silyl ethers to b-siloxy aldehydes has been effected using MABR as a catalyst under mild conditions. Used in combination with the Sharpless asymmetric epoxidation of allylic alcohols, this rearrangement represents a new approach to the synthesis of various optically active b-hydroxy aldehydes, useful intermediates in natural product synthesis (eq 3).5 MABR has also been used to transform a variety of simple epoxides to carbonyl compounds with high efficiency and selectivity.

This approach enables the practical asymmetric synthesis of both erythro and threo aldols based on the MABR-promoted selective rearrangement of optically active threo and erythro epoxy silyl ethers (eq 4).6 The migratory aptitude of alkyl substituents in the Lewis acid-promoted epoxide rearrangement has been investigated with the MABR reagent.7

Intramolecular Ene Reactions.

The intramolecular ene reaction of a-substituted d,ε-unsaturated aldehydes has been executed with high trans selectivity, not observed with ordinary Lewis acids (eq 5).8 This method has been used for the asymmetric synthesis of the cyclohexyl fragment of FK-506.9 Since MABR is also the reagent of choice for epoxide rearrangements, this approach has been directly applied to the cyclization of alkenic epoxides (eq 6).10

a-Primary Alkylation of Ketones.

a-Primary alkylation of carbonyl compounds via the corresponding enol silyl ethers with primary alkyl triflates has been realized in the presence of MABR under mild conditions (eq 7).11 Here, only monoalkylation products are obtained.

Oxetanone Synthesis.

Reaction of Trimethylsilylketene and aldehydes with MABR affords cis-2-oxetanones with high selectivity (eq 8).12 In the case of aromatic and a,b-unsaturated aldehydes, (Z)-2-alkenoic acids are directly obtained via the ring opening of the intermediary cis-2-oxetanones (eq 9).

1. (a) Maruoka, K.; Nonoshita, K.; Banno, H.; Yamamoto, H. JACS 1988, 110, 7922. (b) Nonoshita, K.; Banno, H.; Maruoka, K.; Yamamoto, H. JACS 1990, 112, 316.
2. Nonoshita, K.; Maruoka, K.; Yamamoto, H. BCJ 1992, 65, 541.
3. Maruoka, K.; Banno, H.; Nonoshita, K.; Yamamoto, H. TL 1989, 30, 1265.
4. Maruoka, K.; Sato, J.; Banno, H.; Yamamoto, H. TL 1990, 31, 377.
5. (a) Maruoka, K.; Ooi, T.; Yamamoto, H. JACS 1989, 111, 6431. (b) Maruoka, K.; Bureau, R.; Ooi, T.; Yamamoto, H. SL 1991, 491. (c) Maruoka, K.; Nagahara, S.; Ooi, T.; Yamamoto, H. TL 1989, 30, 5607. (d) Maruoka, K.; Ooi, T.; Nagahara, S.; Yamamoto, H. T 1991, 47, 6983.
6. (a) Maruoka, K.; Sato, J.; Yamamoto, H. JACS 1991, 113, 5449. (b) Maruoka, K.; Sato, J.; Yamamoto, H. T 1992, 48, 3749.
7. Maruoka, K.; Ooi, T.; Yamamoto, H. T 1992, 48, 3303.
8. Maruoka, K.; Ooi, T.; Yamamoto, H. JACS 1990, 112, 9011.
9. Maruoka, K.; Saito, S.; Ooi, T.; Yamamoto, H. SL 1991, 579.
10. Maruoka, K.; Murase, N.; Ooi, T.; Yamamoto, H. SL 1991, 857.
11. Maruoka, K.; Sato, J.; Yamamoto, H. JACS 1992, 114, 4422.
12. Maruoka, K.; Concepcion, A. B.; Yamamoto, H. SL 1992, 31.

Keiji Maruoka & Hisashi Yamamoto

Nagoya University, Japan

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