Lithium aluminum hydride complex with carbonyls

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

The reaction of complex hydrides with carbonyl compounds can be exemplified by the reduction of an aldehyde with lithium aluminum hydride. The reduction is assumed to involve a hydride transfer from a nucleophile -tetrahydroaluminate ion onto the carbonyl carbon as a place of the lowest electron density. The alkoxide ion thus generated complexes the remaining aluminum hydride and forms an alkoxytrihydroaluminate ion. This intermediate reacts with a second molecule of the aldehyde and forms a dialkoxy-dihydroaluminate ion which reacts with the third molecule of the aldehyde and forms a trialkoxyhydroaluminate ion. Finally the fourth molecule of the aldehyde converts the aluminate to the ultimate stage of tetraalkoxyaluminate ion that on contact with water liberates four molecules of an alcohol, aluminum hydroxide and lithium hydroxide. Four molecules of water are needed to hydrolyze the tetraalkoxyaluminate. The individual intermediates really exist and can also be prepared by a reaction of lithium aluminum hydride... 

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

Reduction of unsaturated ketones to unsaturated alcohols is best carried out Nit v complex hydrides. a,/3-Unsaturated ketones may suifer reduction even at the conjugated double bond [764, 879]. Usually only the carbonyl group is reduced, especially if the inverse technique is applied. Such reductions are accomplished in high yields with lithium aluminum hydride [879, 880, 881, 882], with lithium trimethoxyaluminum hydride [764], with alane [879], with diisobutylalane [883], with lithium butylborohydride [884], with sodium boro-hydride [75/], with sodium cyanoborohydride [780, 885] with 9-borabicyclo [3.3.1]nonane (9-BBN) [764] and with isopropyl alcohol and aluminum isopro-... 

Addition of hydride to the carbonyl carbon to form an alcohol, or the reverse, changes the oxidation state and so is usually classified separately from other carbonyl reactions. Some of these processes are nevertheless fundamentally similar to the ones we have been considering. Reductions by complex metal hydrides, such as lithium aluminum hydride or sodium borohydride, are additions ofH - (Equation 8.27) the metal hydride ion is simply a convenient source of this extremely basic species. The carbonyl oxygen takes the place of the hydride in coordination with the boron (or aluminum in the case of an alumino-... 

All reactions and sample preparations are carried out in an inert-atmosphere enclosure under dry nitrogen. Solvents and reagents are dried in the following manner. Benzene, tetrahydrofuran, and n-pentane are freshly distilled from lithium aluminum hydride pyridine is distilled over barium oxide and tetramethylethylenediamine is distilled over calcium hydride. Solvents used in preparing nmr and infrared samples are degassed by a freeze-thaw technique. Nmr spectra are obtained with torch-sealed nmr tubes. The commercial transition metal carbonyl complexes are recrystallized and vacuum-dried before use. Glassware is routinely flame-dried. 

The first chiral aluminum catalyst for effecting asymmetric Michael addition reactions was reported by Shibasaki and coworkers in 1986 [82], The catalyst was prepared by addition of two equivalents of (i )-BINOL to lithium aluminum hydride which gave the heterobimetallic complex 394. The structure of 394 was supported by X-ray structure analysis of its complex with cyclohexenone in which it was found that the carbonyl oxygen of the enone is coordinated to the lithium. This catalyst was found to result in excellent induction in the Michael addition of malonic esters to cyclic enones, as indicated in Sch. 51. It had previously been reported that a heterobimetallic catalyst prepared from (i )-BINOL and sodium and lanthanum was also effective in similar Michael additions [83-85]. Although the LaNaBINOL catalyst was faster, the LiAlBINOL catalyst 394 (ALB) led to higher asymmetric induction. 

Addition of an ethyl group at Cis is a much more complex proposition. The scheme for preparing the 16/3-ethyl derivative begins with Knoevenagel condensation of DHEA acetate (8-1) with acetaldehyde and base to afford the ethylidene derivative 8-2 (Scheme 4.8a). Catalytic reduction adds hydrogen from the bottom side to give 8-3. The carbonyl at C17 is then reduced with lithium aluminum hydride the acetate is also reduced in the process. Reaction with... 

Pierre and Handel have studied the effect of [2.1.1]-cryptate on the lithium aluminum hydride reduction of cyclohexanone in diglyme [16]. The [2.1.1]-cryptate strongly complexes lithium ion and if sufficient cryptate is used to sequester all of the lithium ion, no reduction occurs. Apparently, lithium ion is needed as an electrophilic catalyst for the reduction to occur (see Eq. 12.8). Consistent with this interpretation is the observation that even in the presence of cryptate, reduction will occur if an excess of lithium iodide is also present. The relatively low reactivity of tetrabutyl-ammonium borohydride in benzene solution may also reflect this property, at least in part [9]. Likewise, the jS-hydroxyethyl quaternary ammonium ions may be better catalysts than non-oxygenated quaternary ions because the hydroxyl may hydrogen bond to carbonyl and provide electrophilic catalysis [5]. Similar, though less dramatic results, have been observed in the reduction of aromatic aldehydes and ketones by lithium aluminum hydride in the presence of [2.1.1]-cryptate [17]. 

Addition of deuterium to carbonyl double bonds and their nitrogen analogs is accomplished by complex metal hydrides in an increasing number of examples. In this reduction two deuterium atoms are transferred of course, only the deuterium on carbon is firmly bound, and that attached to the hetero atom can be removed in the usual way. Since such reactions can in general be carried out with LiAlD4 in aprotic solvents, the use of lithium aluminum deuteride, LiAlH4,. offers no peculiarities. The necessary LiAlD4, which is extremely sensitive to hydrolysis, is commercially available. It can be conveniently handled as a solution in a dry dialkyl ether or in tetrahydrofuran at temperatures up to ca. 130°. 

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