Introduction
Trimethylaluminium (or trimethylaluminum, TMA) [CAS Reg. No. 75-24-1] is an organometallic
reagent from the family of alanes, described first in 1939.[1 ] This highly pyrophoric compound is a liquid at room temperature (mp 15 °C) and is
commercialized neat or as a solution in an organic solvent (hexane, heptane, toluene,
chlorobenzene).
This reagent can be prepared, amongst other methods, from aluminium and chloroform,
dimethylaluminium chloride or methylaluminium sesquichloride, treated with sodium
or sodium/potassium.[2 ] The preparation has been industrialized above all by Ziegler,[3 ] who later reported the Ziegler–Natta polymerization with TMA.
This versatile reagent has a high Lewis acid character, much more than zinc or magnesium
organometallic compounds. In addition, the reagent is used as methyl nucleophilic
donor, the cheapest one thanks to its industrial use.
Table 1 Use of Trimethylaluminium
(A) Gremaud and Alexakis accomplished the copper-catalyzed enantioselective 1,4-addition
of TMA on β,γ-unsaturated α-keto esters.[4 ] The reaction was performed with excellent 1,4-regioselectivity, yield, and enantiomeric
excess only with the simple commercially available ligand BINAP.
(B) Alternatively to the well-known zirconium-catalyzed carbometalation of alkynes,
a new regio- and stereospecific scandium-catalyzed methodology was employed by Hou
and co-workers.[5 ]
(C) The Cu-catalyzed enantioselective conjugate addition of a β-alkenylalkylaluminium
reagent (prepared via Ni catalysis) to an α,β-unsaturated ketone (which is issued
by Zr-catalyzed carboalumination using TMA) was reported by McGrath and Hoveyda.[6 ] This multicomponent reaction allowed the enantioselective synthesis of β,β-disubstituted
ketones from alkynes.
(D) Although m -tert -alkylbenzenes are not accessible by traditional Friedel–Crafts reaction, Carlier
and co-workers synthesized this kind of compounds by methylation of activated tertiary
benzylic alcohols using TMA.[7 ] Alcohol activation could be carried out using thionyl chloride or concentrated hydrochloride
solution.
(E) Even though the direct amidation of esters using TMA is a well-known strategy,
Chen and co-workers reported the direct amidation of carboxylic acids using a stoichiometric
amount of TMA. The amide bond formation proceeded with high yields even though bulky
or weakly nucleophilic amines were employed.[8 ]
(F) West and co-workers were able to show that TMA promotes Nazarov reaction on dienones.
Symmetrical dienones afforded cyclopentanone products in good yields as single diastereoisomers.[9 ]
(G) Woodward and co-workers described the 1,2-asymmetric addition of organozinc halides
to aldehydes promoted by TMA. Optimization using an in situ prepared organozinc reagent
afforded higher yields and enantioselectivities.[10 ]
(H) Colby and co-workers proposed a simple carbonyl group differentiation between
an aldehyde and an ester (or ketone). Indeed, if the aldehyde moiety is masked as
an aluminium aminal, a chemoselective addition to the ester (or ketone) moiety is
allowed. In situ unmasking is then performed by hydrolysis or using a Dowex® resin.[11 ]
