Carbonyl groups diisobutylaluminum

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

A structurally unusual 3-blocker that uses a second molecule of itself as the substituent on nitrogen is included here in spite of the ubiquity of this class of compounds. Exhaustive hydrogenation of the chromone (13-1) leads to a reduction of both the double bond and the carbonyl group, as in the case of (11-2). The car-boxyhc acid is then reduced to an aldehyde (13-2) by means of diisobutylaluminum hydride. Reaction of that intermediate with the ylide from trimethylsulfonium iodide gives the oxirane (13-3) via the addition-displacement process discussed earlier (see Chapters 3 and 8). Treatment of an excess of that epoxide with benzylamine leads to the addition of two equivalents of that compound with each basic nitrogen (13-4). The product is then debenzylated by catalytic reduction over palladium to afford nebivolol (13-5) [16]. The presence of four chiral centers in the product predicts the existence of 16 chiral pairs. 

The mechanism of diisobutylaluminum hydride reduction involves formation of a six-membered transition state with aluminum complexed to the carbonyl of the ester group, which is required for the delivery of the hydride from the electrophilic aluminum hydride to the carbonyl group. The alkoxy moiety is then displaced during workup resulting in the desired peptide aldehyde. This mechanism accounts for the fact that the reduction stops after the conversion of the ester into the aldehyde. 23 ... 

The hydride donor with a covalent M—H bond that is very frequently used for reducing carbonyl groups is iBu2AlH (DIBAL stands for diisobutylaluminum hydride). It can be used in ether, THF, toluene, saturated hydrocarbons, or CH2C12. 

Triisobutylaluminum (racemic) is commercially available in toluene solution. Triethylaluminum and related compounds are used, of course, commercially in Ziegler-Natta polymerization. These solutions can be handled safely in contrast to the pure materials, which are violently reactive. The applications of triisobutylaluminum have been reviewed." Its use is difficult to divorce from its chemical relative, diisobutylaluminum hydride, which is probably more often used for reductions of carbonyl groups. This latter reagent reduces, of course, via the reactive aluminum-hydride bond. The thought that the dialkylaluminum is less bulky than the trimer is misleading there is a greater tendency of the former towards aggregation." ... 

Finally, the introduction of additives may allow the stereoselectivity of the reductions to increase. Thus the addition of ZnCl, to Zn(BH4)2 or the coordination of the carbonyl group by a bulky Lewis acid such as diisobutylaluminum 2,6-di-r-Bu-4-methylphenolate (BHT) induces high and opposite stereoselectivities from chiral P-ketoesters 3.135 (Figure 3.46). In the first case, chelation is strengthened, and the reduction involves a cyclic transition state. In the second case, chelation is disfavored, and the other isomer is formed [TDl]. Chelation may also be promoted in reductions of P-ketoesters or amides by addition of TiCl4 [SG2] or MnCl2 in catalytic amounts [FOl]. 

Aluminum enolates can be formed by conjugate addition with diisobutylaluminum hydride (DIBAL-H) and a catalytic amount of methylcopper in a mixture of THF and HMPA (Scheme 28). " The role of copper and HMPA is crucial, for without these 1,2-reduction of the carbonyl group takes place. The effect of copper(l) on conjugate addition is not unexpected. In regard to the solvents it is suggested that HMPA functions not as a cosolvent but as an essential ligand. Treatment of an a. -un-saturated ketone with trimethylaluminum and a catalyst leads to a dimethylaluminum enolate with moderate ( )/(Z) selectivity. The (Z)-enolate reacts with diphenylketene to give another enolate (Scheme... 

Tsuji and coworkers have developed diisobutylaluminum phenoxide-pyridine as an effective aldol condensation catalyst and applied it to the macrocyclization of 2,15-hexadecanedione (equation 132). Addition of the diketone at high dilution to a solution of the catalyst in hexane provides a mixture of cis and trans isomers of the and A enones. Catalytic hydrogenation of the mixture affords ( )-muscone. The authors explain the regioselectivity of the process by assuming that the aluminum phenoxide functions as a Lewis acid, coordinating to the carbonyl group. Pyridine functions as a base to remove a proton from the less hindered methyl group. 

Allylic sulfides 60 were derived from camphor by reacting the enolate with S-allyl thiosulfonates and reducing the carbonyl group with diisobutylaluminum hydride61. Oxidation with peracid leads to the chiral sulfoxides which undergo diastereoselective sigmatropic rearrangements (Section D.7.4.). 

C-1 Selective reduction of malates is not restricted exclusively to the diesters, but succeeds with anhydrides as well. Selective reduction of anhydride 54 at the C-1 site with sodium borohydride affords lactone 55 in 61% overall yield from 7b. A second reduction of the lactone carbonyl with diisobutylaluminum hydride furnishes lactol 56, which is then converted to acetal 57 with 2,2-dimethylpropane-l,3-diol. Introduction of the required acetylene group requires an additional 5 steps. 

In the late 1970s, Jean-Louis Luche and co-workers began to evaluate the role of lanthanide salts in selective organic reductions. Even with the extensive arsenal of available reagents, including sodium cyanoborohydride, diisobutylaluminum hydride and 9-borabicyclononane (9-BBN), there has remained room for improvement in yield, selectivity and reaction conditions in reductions of carbonyl groups in complex organic molecules. 

Diisobutylaluminum hydride converts the amide into an aldehyde. Acidic hydrolysis releases the carbonyl group from the acetal. The product is an oxoalkanal capable of intramolecular aldol condensation under the acidic conditions to give the observed product ... 

The reduction can be carried out in a distereoselective manner also when the chiral group is in Imposition to the carbonyl. Moreover, a reversal of the sense of the diastereoselectivity can be achieved by the use of diisobutylaluminum hydride (dibal-H) or tetramethylammonium triacetoxy-borohydride (Me4NBH(OAc)3) to give 1,3-jyn or l,3-anti diols, respectively (Scheme 34) <93S903>. 

The furanone 42, although commercially available, could also be obtained in large amounts by epoxidation of 3,3-dimethyl-4-pentenoic acid with 3-chloroperoxybenzoic acid (MCPBA) in chloroform at room temperature (84%). After protection of the primary alcohol 42 as a benzyl ether, the carbonyl unit was reduced with diisobutylaluminum hydride in ether at -78 °C to afford the diastereomeric pair of lactols 43 in 97% yield and a ratio of approximately 2 1. The lactols were methylated with p-toluene sulfonic acid in methanol to provide the functionalized tetrahydrofurans in nearly quantitative yield. The benzyl group was removed by hydrogenolysis over palladium hydroxide on carbon to afford the alcohols 44 in 94% isolated yield use of other catalysts, such as palladium on carbon, gave less reproducible results. 

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