Alkoxyaluminum hydride reductions

Reduction of o /i-unsatin-ated lactams, S,6-dihydro-2-pyridones, with lithium aluminum hydride, lithium alkoxyaluminum hydrides and alane gave the corresponding piperidines. 5-Methyl-5,6-dihydro-2-pyridone (with no substituent on nitrogen) gave on reduction with lithium aluminum hydride in tetrahydrofuran only 9% yield of 2-methylpiperidine, but l,6-dimethyl-5,6-dihydro-2-pyridone and 6-methyl-l-phenyl-5,6-dihydro-2-pyridone afforded 1,2-dimethylpiperidine and 2-methyl-1-phenylpiperidine in respective yields of 47% and 65% with an excess of lithium aluminum hydride, and 91% and 92% with alane generated from lithium aluminum hydride and aluminum chloride in ether. Lithium mono-, di- and triethoxyaluminum hydrides also gave satisfactory yields (45-84%) [7752]. 

For reviews of reductions with alkoxyaluminum hydrides, see M4lek Org. Read. 1988, 36, 249-590, 1985, 34, 1-317 MSIek Cerny Synthesis 1972, 217-234. 

A general method for the synthesis of 2-deoxyaldoses utilizes a reaction sequence involving the formation and subsequent reduction of ketene dithioacetal intermediates (Scheme 10). Reduction of ketene diethyl dithioacetal 12 with lithium aluminum hydride proceeds via the alkoxyaluminum hydride salt involving the 3-hydroxyl group. Several deoxy hexoses and pentoses were prepared by this method, and also their 2-deuterio analogues.45... 

J. Malek, Reduction by Metal Alkoxyaluminum Hydrides. Part II. Carboxylic Acids and Derivatives, Nitrogen Compounds, and Sulfur Compounds, Org. React. 1988, 36, 249-590. 

Based on the accompanying kinetic data and an observation that lithium cation is essential in the lithium aluminum hydride reduction,5 Ashby and Boone proposed that the reduction would occur via a six-membered transition state in which the lithium cation is involved4 (Scheme 4.II). Because the aluminum in the boat transition state TS-boat is proximal to the carbonyl oxygen, the boat transition state might be of lower energy than the chairlike transition state TS-chair. Furthermore, the boatlike transition state would be a favored states as it results in direct formation of the lithium alkoxyaluminum hydride intermediate. 

The enantioselective reduction of unsymmetrical ketones to produce optically active secondary alcohols has been one of the most vibrant topics in organic synthesis.8 Perhaps Tatchell et al. were first (in 1964) to employ lithium aluminum hydride to achieve the asymmetric reduction of ketones9 (Scheme 4.IV). When pinacolone and acetophenone were treated with the chiral lithium alkoxyaluminum hydride reagent 3, generated from 1.2 equivalents of 1,2-0-cyclohexylidene-D-glucofuranose and 1 equivalent of LiAlHzt, the alcohol 4 was obtained in 5 and 14% ee, respectively. Tatchell improved the enantios-electivity in the reduction of acetophenone to 70% ee with an ethanol-modified lithium aluminum hydride-sugar complex.10... 

Asymmetric reduction of (5s)-sulfmimine 110 with diisobutylaluminum hydride (DIBAL) afforded a diastereomeric mixture of sulfinamides 111 in 92% yield and in a ratio of 96 4.34 Use of sodium boron hydride, lithium aluminum hydride, or lithium alkoxyaluminum hydride resulted in lower optical yields.33,34,75 The sul-finyl group can be removed by treating 111 with trifluoroacetic acid (TFA) and methanol to give a-phenylethyl amine (112). 

Reductions by Metal Alkoxyaluminum Hydrides Jaroslav Males... 

A comparison of four tri-f-alkoxyaluminum hydrides revealed that lithium tris[(3-ethyl-3-pen-tyl)oxy]aluminum hydride, prepared from LAH and 3-ethyl-3-pentanol, was the most selective for reduction of aldehydes over ketones of all types. Even the less reactive benzaldehyde was reduced in THE at -78 C faster than cyclohexanone (97.7 2.3). A good correlation between the steric demands of the reducing agent and the observed chemoselectivity was observed. 

Alkoxyaluminum hydrides including Red-Al, Li(Bu 0)3AlH and Li(MeO)3AlH have been used extensively, particularly for the reduction of o-quinones to the corresponding o-hydroquinones. It appears that the use of more soluble reagents and powerful ethereal solvents also favors reduction to the hydro-quinone. ... 

A number of reviews which relate to reduction in general and only in part to the types of reduction presently being considered may also be of interest to the reader. These include a review of hydride reductions in general by Brown and Krishnamurthy and of metal alkoxyaluminum hydrides in particular by Malek. ° The important role of electrophilic catalysis in achieving reductive S—O bond cleavage is summarized in a review of the applications of iodotrimethylsilane by Olah and Narang. ... 

The properties of complex metal hydrides, particularly those of aluminum, and their use in organic synthesis have been compared in a number of papers, review articles and monographs. " ° Useful tables, listing the most appropriate hydride reagents for selective reduction of various polyfunctional compounds, have been published. " Use of chiral metal alkoxyaluminum hydride complexes in asymmetric synthesis has also been reviewed. ... 

Asymmetric reductions of saturated and unsaturated carbonyl compounds are performed either with alkoxyaluminum hydrides or alkoxyboron hydrides bearing chiral substituents, with chiral boranes, or with achiral boranes in the presence of stoichiometric or catalytic amounts of oxazaborolidines [602, 604, 611] (see Chapter 2). The most efficient chiral alkoxyaluminum hydrides [87, 566] are generated in situ from solutions ofLiAfflU by addition of (17 ,23)-A -methylepkedrine... 

L Reductions by Metal Alkoxyaluminum Hydrides Jaroslav Malek 2. Fluorination by Sulfur Tetrafluoride Chia-Lin J. Wang... 

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