Hydride, diisobutylaluminum carbonyls

The major obstacle to this approach is that there are few reagents capable of generating higher homologues of titanocene-methylidene. Although the procedure is not straightforward, the titanacycle 21 formed by the addition of diisobutylaluminum hydride to the double bond of (l-propenyl)titanocene chloride 22 serves as a titanocene-propylidene 23 equivalent in carbonyl olefmation (Scheme 14.12) [22]. 

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. 

Arenediazonium tetrafluoroborates, 19 Azidotrimethylsilane, 24 N-Chlorosuccinimide, 79 Diphenyldiazomethane, 242 a-Substituted a-amino acids a-Methylbenzylamine, 185 Methyl N-benzyloxy carbonyl-a-chloro-glycinate, 186 Pivaldehyde, 249 Miscellaneous compounds Diisobutylaluminum hydride-Boron trifluoride etherate, 116 Tin(IV) chloride, 300 Amino alcohols... 

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. 

Diisobutylaluminum benzenetellurolate, prepared from diphenyl ditellurium and diisobutylaluminum hydride, adds in a 1,4-fashion to a,/i-unsaturated aldehydes, ketones, and carboxylic acid esters to give as intermediates /i-phenyltelluro-substituted aluminum enolates that can be hydrolyzed to the carbonyl compounds or reacted with aldehydes to produce aldol adducts2. 

AD-mix-P 9-BBN Bn Boc Bz BOM CDI m-CPBA CSA Cy DBU DDQ DEAD DIAD DIBAL-H DIPT DME DMF DMAP DMSO EDC HMPA HOBT KHMDS LDA MEM MOM MoOPH NaHMDS NBS NMM NMO Piv PMB Reagent for Sharpless asymmetric dihydroxylation 9-Borabicyclo[3.3.1 ]nonyl Benzyl t-Butoxy carbonyl Benzoyl B enzyloxy methyl Carbonyldiimidazole m-Chloroperoxybenzoic acid Camphorsulfonic acid Cyclohexyl 1,8 -Diazabicy clo[5.4.0] undec-7-ene 2,3 -Dichloro-5,6-dicyano-p-benzoquinone Diethyl azodicarboxylate Diisopropyl azodicarboxylate Diisobutylaluminum hydride Diisopropyl tartrate Dimethoxyethane A,N-Dimethylformamide 4-Dimethylaminopyridine Dimethyl sulfoxide N-(3-Dimethylaminopropyl)-A -ethylcarbodiimide Hexamethylphosphoramide 1 -Hydroxybenzotriazole Potassium hexamethyldisilazane Lithium diisopropylamide Methoxyethoxymethyl Methoxymethyl Oxidodiperoxymolybdenum(pyridine)(hexamethylphophoramide) Sodium hexamethyldisilazane N - Bromosuccinimide A-Methylmorpholine A-Methylmorpholine A-oxide Pivaloyl /j-Methoxybenzyl... 

Efficient conjugate reduction of several a,/8-unsaturated carbonyl substrates was similarly realized by combining ATPH with diisobutylaluminum hydride-BuLi ate complex (DIBAH-BuLi) as a reducing agent [144]. Diisobutylaluminum hydride-t-BuLi was more effective for the 1,4 reduction of a,/ -unsaturated aldehydes, as illustrated in Sch. 105. 

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." ... 

Diisobutylaluminum hydride reacts chemoselectively with a triple bond in competition Vv ith a double bond in enynes. However, a carbonyl moiety contained in an alkyne is reduced preferentially. 

Diisobutylaluminum hydride (DIBAH) is undoubtedly one of the most common reducing agents in organic synthesis and recent interest in the synthetic utility of DIBAH has been directed toward diastereoselective reduction of carbonyl substrates. High, i-syn diastereoselectivity has been achieved in the chelation-controlled reduction of P-hydroxy ketones with DIBAH in THF [49], The choice of solvents strongly affects the selectivity. Use of CH2CI2 or toluene in place of THF did not show any diastereoselectivity. 

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>. 

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... 

Ethynylnickel compounds, prepared from aluminum acetylides and nickel acetylace-tonate pretreated with diisobutylaluminum hydride, also undergo insertions with a, 8-unsaturated carbonyl compounds to form enolates which hydrolyze to 4-ynones . Similarly, vinylnickel derivatives from vinylzirconium compounds and nickel acetylace-tonate add to a, 8-unsaturated ketones to give enolates ... 

Particularly satisfying was the ease with which 157 was homologated to 158 (92%). Reduction of the ketone carbonyl in a chemoselective manner was not possible because of the steric protection it benefits from. This potential complication was skirted when it was found that the hydroxy lactol produced by diisobutylaluminum hydride reduction responded to the Fetizon reagent only at the five-membered site to deliver 159. With the stereochemistry of 159 securely established by NOE analysis, no obstacles were encountered during acetylation and the subsequent completion of sidechain construction. 

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. 

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. 

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