Sodium Bis(2-methoxyethoxy)aluminum Hydride1

NaAlH2(OCH2CH2OMe)2

[22722-98-1]  · C6H16AlNaO4  · Sodium Bis(2-methoxyethoxy)aluminum Hydride  · (MW 202.19)

(reducing agent for many functional groups;1 methylation reagent for aryl-activated compounds;19 can function as a base;21 can hydroaluminate alkenes and alkynes22)

Alternate Names: SMEAH, Red-Al®, Vitride.

Physical Data: fp 4 °C (3.4 M toluene solution); d 1.036 g cm-3 (3.4 M toluene solution), d 1.122 g cm-3 (solid); highly viscous liquid at rt; thermally stable up to 205 °C, upon which vigorous decomposition starts.

Solubility: sol aromatic hydrocarbons, ether, THF, DME; insol aliphatic hydrocarbons.

Form Supplied in: 3.4 M solution in toluene. 145 g contains 1 mol of active hydride. The pure compound is a slightly yellow, glassy solid.

Analysis of Reagent Purity: concentration can be determined by iodometric titration.

Handling, Storage, and Precautions: highly flammable; moisture sensitive; reacts less strongly with H2O than LiAlH4; potent skin irritant. Use in a fume hood.

Functional Group Reductions.

SMEAH has reducing properties fully comparable to Lithium Aluminum Hydride, making it a valuable alternative reducing reagent.1,2 Some practical advantages of SMEAH are that it does not ignite when exposed to moist air or O2, has greater solubility in aromatic solvents and ethers, and reactions can be carried out at higher temperatures (up to 200 °C). Carboxylic esters, acids, acid chlorides, anhydrides, aldehydes, and ketones are efficiently converted to the alcohol. Cyclic anhydrides and lactones yield diols. Carboxylic esters are not reduced at -78 °C and t-Bu and Ph esters are generally stable to SMEAH at low temperature.

Nitriles, amides, imines, azido compounds, nitro compounds, isocyanates, urethanes, sulfonamides, oximes, lactams, and imides can be reduced to the amine. The formation of aziridines can complete with simple reduction of ketoximes and their O-alkyl derivatives. Nitroarenes form azoxyarenes, azoarenes, or hydrazoarenes depending on reaction conditions.3

Alkanesulfonates can be converted to alkanes or to alcohols. Phosphate esters afford the alcohol.4 Some epoxides can be reduced to the alcohol (temperatures above 0 °C are required). Disulfides give thiols while sulfoxides yield sulfides. Sulfones are generally inert or give low yields of sulfides. Haloalkanes, haloarenes, and organosilicon halides undergo hydrogenolysis to the alkane, arene, and silane, respectively.5 Benzylic aldehydes or alcohols, aryl alkyl or diaryl ketones, and aryl acids containing strong electron donating groups in the ortho or para position also undergo hydrogenolysis at 120-140 °C.6 Acetals are usually stable toward hydrogenolysis or elimination at 0-20 °C, except in the presence of a conjugated double bond and bromide (eq 1)7a or in certain quinone monoacetal systems.6b

Partial Reductions.

Low-temperature conditions or the use of alcohol or amine-modified SMEAH have proven especially valuable for partial functional group reductions.1,2 Carboxylic esters, nitriles, and amides can be reduced to the aldehyde at low temperatures. The morpholine or N-methylpiperazine modified reagent also yields aldehydes at -55 to 0 °C.8,9 Lactones are converted to lactols by unmodified SMEAH at -70 °C2b or with the EtOH, pyridine, or i-PrOH modified reagent at 0 °C. N-Substituted cyclic imides provide hydroxylactams upon reduction at -78 °C.10 It is the reagent of choice for the reduction of Cp2ZrCl2 to Cp2ZrClH.11

Selective Reductions.

Vinylogous amides have been selectively reduced to the b-ketoamine (eq 2).12a SMEAH is superior to LiAlH4 for the reduction of acetal-protected cyanohydrins to the aldehyde.12b It chemoselectively reduces a-formyl ketones to the a-hydroxymethyl ketone.12c Lactones are stable in the presence of ketone or aldehyde functionality at low temperatures. SMEAH modified by alcohols or in pyridine solvent selectively reduces lactones in the presence of an amide or ester.13a Ester groups in amidoesters undergo selective reduction at 0 °C and short reaction times.13b SMEAH gives higher yields than LiAlH4 in the reduction of some hydroxy-substituted carbonyl compounds (eq 3).13c 5,5-Disubstituted hydantoins are selectively reduced at the 4-position13d and keto aldehydes have been cleanly reduced to the keto alcohol.13e Optically active a-alkoxy carboxamides have been reduced to the a-alkoxy aldehydes without racemization.13f

1,2-vs. 1,4-Reductions.

The structure of the enone, solvent, relative initial concentrations, temperature, and softness or hardness of the hydride reagent all play a role in controlling the mode of addition to enone systems. SMEAH typically acts as a hard hydride, favoring 1,2-addition in these reactions. High yields of the allylic alcohol have been reported by inverse addition of the hydride to aliphatic or alicyclic a,b-unsaturated aldehydes and esters.14a,b It favors 1,2-addition to cyclic a-enones and is the reagent of choice for the low-temperature reduction of enol esters of alicyclic 1,3-diketones (eq 4).14c Alkyl esters are not reduced under these conditions. The SMEAH/CuBr/2-butanol reagent is extremely efficient for 1,4-reduction.15 Nitrile and ester functions are stable under the conditions of the conjugate reduction, while aldehydes, ketones, and bromides are attacked by the complex.

Stereoselective Reductions.

The stereochemistry of reductions often varies, depending on the solvent. A possible factor is the degree of solvation. In some cases, complete reversal of stereochemistry has been observed by using SMEAH in benzene versus THF.1 In comparison to other reducing agents, SMEAH often shows stereoselectivity opposite to that of LiAlH4, Sodium Borohydride, or lithium trialkoxyaluminum hydrides. Unsymmetrical epoxides are attacked preferentially at the least-substituted carbon atom to give the more highly substituted alcohol as the major product.16a Exceptionally high regioselectivity in the reduction of a,b-epoxy alcohols to the 1,3-diol has been observed (eq 5).16b-e Substituents at the a-carbon reverses the selectivity and decreases the reaction rate. The reduction of a-silyloxy ketones produces syn-vicinal diols with high levels of diastereoselectivity.16f,g

SMEAH reacts with bridged bicyclic ketones from the less hindered side of the carbonyl.17a Reduction of gem-dihalocyclopropanes gives anti-monohalides as the major product.17b It reduces a-alkynic alcohols to trans-allylic alcohols with high selectivity.18a-d Alkynyl ethers give almost exclusively O-alkyl enol ethers with the (E) configuration with SMEAH, but with alcohol-modified SMEAH reagent (Z)-enol ethers are obtained (eq 6).18e

Methylation Reagent.

The reduction of aryl-conjugated double bonds yields selective methylation at the more highly arylated carbon atom.19 The Me group originates from the hydride OMe group. Aryl-activated alkanes undergo methylation by this reagent. Diaryl and condensed aromatic ketones undergo hydrogenolysis and subsequent methylation at the benzylic carbon.

Reductive Cleavage of Ethers.

Ethers are usually stable at temperatures below 100 °C. At higher temperatures, cleavage of the ether linkage occurs. SMEAH is a useful reagent for debenzylation and deallylation of aryl benzyl and aryl allyl ethers (eq 7).20 The reaction is enhanced by a vicinal methoxy group. This method is recommended for debenzylation and deallylation of phenolic ethers that are labile to acid or catalytic hydrogenolysis.

Use as a Base.

SMEAH can act as a strong base. It is known to promote isomerization and dehydrogenation of aromatic hydrocarbons by a base-catalyzed reaction.21a,b The Stevens rearrangement of berbine methiodide affords the spiroisoquinoline derivative in high yield.21c

Hydroalumination Reagent.

Double and triple bonds undergo catalytic hydroalumination with a number of aluminum hydride reagents.22 The effectiveness of SMEAH in this reaction is comparable to that of LiAlH4, NaAlH4, NaAlHMe3, LiAlH2(NR2)2, or NaAlH2(NR2)2.

Related Reagents.

Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride.


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Melinda Gugelchuk

University of Waterloo, Ontario, Canada



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