DIBAH reduction

Stille coupling (12, 56).1 The key step in a synthesis of (E)-neomanoalide (4) involves palladium-catalyzed coupling of an allyl halide with an a-stannylfuran. Thus 1 and 2 couple in the presence of Pd(dba)2 and P(C6H5), to form 3 as a 1 1 mixture of (E)- and (Z)-isomers in 66% yield. Conversion of 3 to 4 involves reduction (DIBAH) and selective singlet oxygen oxidation of a 2-silylfuran to a butenolide. 

Regioselective lithiation.1 This complex undergoes selective lithiation at the orf/io-position, which can be trapped by methylation to give (2-methylpyridine)tri-carbonylchromium. The disilyl complex 2 undergoes selective lithiation at C4 because of steric effects. Reduction (DIBAH) of 1 provides (l,2-dihydro-pyridine)tri-carbonylchromium (3) after quenching (MeOH). Reaction of 1 with RLi followed by alkylation with CH3I provides the complex 4. 

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. The partial reduction of an ester by dhsobutylaluminum hydride (DIBAH), for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways. The reaction is normally carried out at —78 °C (dry-ice temperature) in toluene solution. 

A TEA/DIBAH mixture can be added to cold (-78°C) monomer until the stable colored complex forms. The purification reaction is then allowed to proceed for 60 minutes at room temperature. This procedure allows for removal of impurities without reduction of the ester. Significantly narrower gel permeation chromatograms (Mw/Mn <1.25) of poly(t-butyl methacrylate) are obtained when the samples are prepared from TEA/DIBAH purified monomer. 

C gives a mixture of dibromoketones 166a and 166b, and when these are treated with zinc-copper in methanol saturated with ammonium chloride at room temperature, the debromination product 167 is obtained in quantitative yield. Reduction of 167 with an excess of DIBAH in THF at — 78°C and then at room temperature leads to a mixture of the 6,7-dehydro-3-hydroxytropanes 168 and 169 (93 7 ratio) (Scheme 10). 

Hayashi, M., Yoshiga, T., Nakatani, K. et al. (1994) Reduction of or-trialkylsiloxy nitriles with diisobutylalu-minium hydride (DIBAH) a facile preparation of (t-lrialkylsiloxy aldehydes and their derivatives. Tetrahedron, 50, 2821-2830. 

Selective reduction of ketones.1 This reagent can be used to effect selective reduction of the more hindered of two ketones by DIBAH or dibromoalane. Thus treatment of a 1 1 mixture of two ketones with 1-2 equiv. of 1 results in preferential complexation of the less hindered ketone with 1 reduction of this mixture of free and complexed ketones results in preferential reduction of the free, originally more hindered, ketone. An electronic effect of substituents on a phenyl group can also play a role in the complexation. This method is not effective for discrimination between aldehydes and ketones, because MAD-complexes are easily reduced by hydrides. MAD can also serve as a protecting group for the more reactive carbonyl group of a diketone. The selectivity can be enhanced by use of a more bulky aluminum reagent such as methylaluminum bis(2-f-butyl-6-( 1,1-diethylpropyl)-4-methylphenoxide). 

Pentitol synthesis An asymmetric synthesis of L-arabinitol involves condensation of the (E)-a,fJ-unsaturated ester (2) with the anion of methyl (R)-p-tolyl sulfoxide (1). The resulting p-keto sulfoxide (3) is reduced stereoselectively by ZnCl2/DIBAH (13, 115-116) to 4. Osmylation of 4 with (CH,)3NO and a catalytic amount of 0s04 (13, 224-225) yields essentially a single triol (5). Finally, a Pum-merer rearrangement of the sulfoxide followed by reduction of an intermediate... 

Scheme 2.46 Synthesis of natural products by reduction of propargylic electrophiles with aluminum hydrides. DIBAH = diisobutylaluminum hydride ...

Recently, diisobutylaluminium hydride (DIBAH) was found to be a selective reducing agent in the reduction of steroidal 5,7 and 22,24(28) dienes (equation 32)100. 

The synthesis of the non-natural ( )-7,14-epz-l(15),8-dolastadien-7,14-ol (rac-7yl4-epi-l09) was published by Paquette in 1986 and is highlighted by a photochemical rearrangement of the 6,6,6-tricyclic a,yS-epoxy ketone 148 into the 5,7,6-tricyclic dolastane skeleton (149) (Scheme 23) [84]. The succeeding hydroxylation of carbon atom by photo oxygenation with singlet oxygen as well as a DIBAH reduction of a keto function proceeded with an undesired substrate-induced diastereoselectivity to provide the racemic 7,14-epimer of the natural dolastane 109. 

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

The synthesis of (-t-)-benzoylselenopederic acid (569) (477) (Scheme 71), the left-hand half of pederin (147), began with (-f-)-3-keto imide 570, which was subjected to the recently developed syn-directing Zn(BH4)2 reduction (482) to give 5yn-a-methyl-3-hydroxy acid derivative 571. Imide 571, after protection of the hydroxyl group as the THP ether, was reduced with DIBAH, and the resulting aldehyde was treated with lithium enolate of tm-butyl acetate to give the p-... 

Aldehydes are prepared by the hydroboration-oxidation of alkynes (see Section 5.3.1) or selective oxidation of primary alcohols (see Section 5.7.9), and partial reduction of acid chlorides (see Section 5.7.21) and esters (see Section 5.7.22) or nitriles (see Section 5.7.23) with lithium tri-terr-butox-yaluminium hydride [LiAlH(0- Bu)3] and diisobutylaluminium hydride (DIBAH), respectively. 

Primary and tertiary alcohols are obtained conveniently from esters by the reduction of LiAlH4 and two molar equivalents of organometallic reagents (R MgX or R Li), respectively (see Sections 5.7.22 and 5.5.5). A less powerful reducing agent, diisobutylaluminium hydride (DIBAH), reduce an ester to an aldehyde (see Section 5.7.22). 

Reduction of nitrile with a less powerful reducing reagent, e.g. DIBAH, produces aldehyde. The reaction is carried out at low temperatures (—78 °C) in toluene. 

Reduction of attenes.1 DIBAH preferentially reduces the more substituted double bond of an allene. Actually the hydride may attack the less substituted double bond and an allylic rearrangement during hydrolysis may be involved. The reduction of 1,1-diphenylallene2 follows a different course, but may represent a special case. 

Lactones - ethers, y- and (5-Lactones can be converted into tetrahydrofuranes and tetrahydropyrancs, respectively, by a two-step procedure. The first step is the well-known reduction of lactones to lactols with DIBAH (1, 261 2, 140). The second step is deoxygenation of the alcohol with triethylsilanc and BF3 etherate.1 This reaction is compatible with several other functional groups, even including hydroxyl groups. 

It was also possible to prepare a variety of deoxy analogs of 10 and 12 by reduction of the lactone carbonyl with DIBAH, and further reduction of the corresponding lactols with Et3SiH and BF3 OEt2 (Figure 9.7). The resultant deoxoartemisinin analogs 14, substituted at 3 and 9, have been reported.26... 

Reduction of ketosulfoxides with DIBAH in the presence ofZnCl2... 

Diastereoselective reduction of chiral -keto sulfoxides (11,291-292). Chiral p-keto sulfoxides 1, prepared by reaction of p-(tolylsulfinyl)methyllithium with esters, are reduced by DIBAH in THF diastereoselectively to (R,S)-2. In the presence of ZnCl2, the opposite diastereoselectivity obtains. The paper includes a new method for conversion of these p-hydroxy sulfoxides into chiral epoxides.1... 

Asymmetric reduction of ketones.2 A reducing agent prepared by treatment of a mixture of SnCl2 and (S)-l-[l-methyl-2-pyrrolidinyl]methylpiperidine (11, 525, 12, 490) with DIBAH effects asymmetric reduction of prochiral ketones in 60-80% ee (equation I). 

Titanium(III) chloride-Diisobutylaluminum hydride. A black, solid lower-valent titanium reagent (1) is obtained on reduction of TiCl3 3THF with DIBAH in toluene.1... 

Recently, Schwartz and Shoer have described the use of (C5H5)2ZrCl2 as a catalyst in the reduction of CO by diisobutylaluminum hydride (DIBAH) (81). The products of this reaction, after aqueous acid workup, were methanol, ethanol, 1-propanol, and 1-butanol in decreasing amounts. A labeling... 

A total of three equivalents of DIBAH and two equivalents of CO are consumed in each run with eventual precipitation of (C5H5)2ZrCl2. The sequence can be repeated with no loss of activity. This system may provide valuable insight into the notion of chain growth in CO reduction chemistry despite the fact that H2 is not employed directly as the reductant. 

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

The enantiomer ent-2 is also easily accessible from 5 by methyl es-ter/diethylamide exchange and subsequent esterification with diazomethane to 23 followed by DIBAH reduction 11... 

Numerous reducing agents were tried at this point unsuccessfully. For example, lithium aluminum hydride destroyed the substrate, whereas DIBAH or lithium borohydnde in THF and sodium borohydride in ethanol led to reduction of the quinoline system. On the other hand, both potassium borohydride (either with or without 18-crown-6) and zinc borohydride (with or without ethanol) produced no reaction at all. Lithium triethylborohydride resulted in de-methoxylation, and sodium borohydride in refluxing THF gave a 45% yield of diol 16 together with overreduced product. 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

The hemiacetal exists as an equilibrium mixture of cyclic compound 20 and its open counterpart (21), but an aldehyde addition reaction can occur only with the acyclic form A Wittig reaction of the stabilized ylide leads to an a. (3-unsaluraied ester that has the configuration with respect to the double bond. This reaction occurs under neutral conditions, so 1,4-addition of the alcohol to the a.p-unsaturated ester is avoided.6 A subsequent DIBAH reduction leads to ally lie alcohol 6 in a reaction that ordinarily shows complete 1,2-selectivit. ... 

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