Epoxidations diisobutylaluminum hydride

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. 

Epoxidation. The last steps in a total synthesis of pentalenolactone (3) required epoxidation of 1, The reaction of alkaline hydrogen peroxide with 1 afforded mainly the undesired -epoxide, epimeric with 2. The desired reaction was effected by reduction of 1 with diisobutylaluminum hydride to the allylic hemiacetal and application of the Sharpless epoxidation reaction. After reoxidation (Jones reagent), the desired epoxide 2 was obtained in 45% yield. Alkaline hydrolysis then gave the natural product (3). ... 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

The reverse regiocontrol, giving 1,2-diols, is observed with DIBAL-H (diisobutylaluminum hydride). The remarkable effect of titanium tetraisopropoxide as an additive to lithium borohydride has also been reported. In this reaction benzene is a better solvent than THF, probably because a Ti complex using both oxygens in epoxy alcohols is formed in benzene before the hydride attack. Other metal hydrides used include sodium hydrogen telluride (NaHTe) and an ate complex derived from DIBAL-H and butyllithium, both of which reduce epoxides to alcohols, although they have been tested with only a small number of examples. In the former case the reaction may proceed via a 2-hydroxyalkyltellurol intermediate. 

Wittig olefination of D- or L-glyceraldehyde acetonide with Ph3P=CHCHO gives, after reduction of the enal with diisobutylaluminum hydride, ( )-allylic alcohols that undergo Katsuki-Sharpless enantioselective epoxidation [255,256,257]. The method has been applied to prepare D-arabinitol (=D-lyxitol) and ribitol (a meso alditol) and D-arabinitol (or xylitol, another meso alditol) [258],... 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

Blattellastanoside B (172) was also synthesized as shown in Figure 7.14.15 Reduction of the chloro epoxide A with diisobutylaluminum hydride was followed by acetylation to give B selectively, although the yield was only 29% with 68% of the recovered A. Treatment of B with sodium methoxide in methanol at 0°C yielded C, which afforded epoxy alcohol D by further treatment with sodium methoxide at 60 °C. Glucosylation of C with acetobromo-D-glucose was followed by deacetylation to give blattellastanoside B (172) as microcrystalline powder, mp 158-160°C. A comparison of the H- and 13C-NMR spectra of the synthetic 172 with those of blattellastanoside B proved the identity. 

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. 

The a,j5-unsaturated -lactone 1107 is constructed by Ghosez s methodology, which involves treating the epoxide with the lithio anion of methyl-3-phenylsulfonyl orthopropionate followed by acid hydrolysis and DBU-induced elimination. Reduction of the lactone to a lactol with diisobutylaluminum hydride and subsequent C-glycosidation furnishes aldehyde 1108 with a 4 1 epimeric ratio. This is then carried on to the desired fragment 1109. 

In this case, diol 66 was converted into the monobenzoate 67 and was epox-idized at the trisubstituted double bond. The epoxide was reduced and the triol obtained was ozonolytically degraded to the lactone of olivomycosonic acid (68). The half-reduction of the lactone 68 with diisobutylaluminum hydride (DIBAH) furnished 63. 

With the two methyl stereocenters successfully set, we next focused on installing the secondary C4-hydroxyl group. Using selenium dioxide, we were able to convert the allylic methyl ether in one step into an enal (174), which we then reduced with diisobutylaluminum hydride (175, Scheme 32). This allylic alcohol could be epoxidized with /m-CPBA, thus ensuring installation of the desired C4-hydroxyl group stereocenter under substrate-controlled conditions... 

Conjugated ester 6.271 was treated with diisobutylaluminum hydride to reduce the ester moiety to an alcohol. This allylic alcohol was subjected to Sharpless asymmetric epoxidation. 1 Opening the epoxide (5.272) with azide was followed by protection of the diol moiety to give 5.273.154 Reduction of the azide, protection of the amine, and oxidation gave lactam 5.274.154 Acid hydrolysis gave 4-amino-2,3-dihydroxy-3-methylbutanoic acid, 6.275, a degradation product of carzinophilin.i55[Pg.231]

The stereochemical information is introduced by (J )-methyl p-toluenesulfoxide 110. This compound is deprotonated with lithium diisopropylamide and reacted with a-chloro methylacetate 109 to give a-chloroketone 111. This ketone when reacted with diisobutylaluminum hydride at —78°C gives (J )-chlorohydrine 112, whereas reaction of ketone 111 with diisobutylaluminum hydride and zinc chloride gives the corresponding (S)-chlorohydrine 113. Treatment of both chlorohydrines with potassium carbonate resulted in the formation of epoxides 114 and 116. These can now be reacted with either (Z)- or (T)-vinyl cuprates to give the desired homoallylic alcohols 115 and 117 in diastereomeric excesses around 90%. 

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