Ester with DIBAL

A similar mechanism is operative in the reduction of carboxylic esters with DIBAL (Figure 17.61). The tetrahedral intermediate A is formed by addition of an A1—H bond of the reducing agent to the ester C=0 bond. This tetrahedral intermediate A does not necessarily decompose immediately to an aldehyde and ROAl(iBu)2. In nonpolar media, A definitely decomposes quite slowly. In fact, at very low temperatures A remains unchanged until it is protonated to a hemiacetal during aqueous workup. The latter eliminates water to give the aldehyde. 

The use of DIBAL-H to reduce nitriles to aldehydes has been added, as has the low-temperature reduction of esters with DIBAL-H to produce aldehydes. Several problems have been added that include these reactions in synthesis. 

The configurationally unstable diethyl 3-(S)-tert-butoxycarbonylamino-3-formylphosphonate is prepared in 80% yield by low-temperature reduction of the corresponding methyl ester with DIBAL-H in toluene and subsequent hydrolysis with 1 M HCl. ... 

Conversion of D to (+)-testudinariol A (149) is summarized in Figure 6.8. After reduction of D with DIBAL-H, the resulting aldehyde E was treated with dimethylaluminum chloride in dichloromethane to give the cyclized product F after TBS protection. Ketone G, prepared from F, was then treated with a chiral phosphonoacetate H in the presence of NaHMDS to give the desired (Z)-ester as the major product. Reduction of the (Z)-ester with DIBAL-H furnished I. Alcohol I was converted to bromide J and sulfone K, respectively. Alkylation of K with J afforded L. Its reductive desulfonization and silyl deprotection yielded (+)-testudinariol A (149) in 4.4% overall yield based on A (19 steps). The spectroscopic... 

Recently, an intramolecular 1,3-dipolar cycloaddition of transient enantiomerically pure oxa-alkenyl nitrones illustrated a synthesis of enantiomerically pure 3,7-dioxa-2-azabicyclo-[3.3.0]octanes. Treatment of (5)-112 with allyl bromide or cinnamyl chloride in diethyl ether in the presence of silver(I) oxide affords the alkylated esters 173 and 174, respectively. No racemization occurs in this process, as determined by proton nmr. Reduction of the esters with DIBAL at — 72 °C provides the corresponding aldehydes, which are immediately reacted with JV-alkylhydroxylamines in order to minimize racemization. The resulting nitrones 175 cannot be isolated, but undergo spontaneous intramolecular 1,3-dipolar cycloaddition to the enantiomerically pure 3,7-dioxa-2-azabicylo[3.3.0]octanes 176a-d (Scheme 40) [48]. 

The diastereomeric retinaldehyde derivatives (394), (395), (396), and (397) were synthesized from the ketone (390) by the following procedure (Nakanishi et aL, 1976) The allenic ketone (390) was reacted with the C2 phosphonate (167) to give the mixture of ester isomers (391), which was reduced with di-isobutylaluminum hydride (DIBAL) and then oxidized with manganese dioxide. The 9 -cis aldehyde (392) was separated by chromatography and was reacted with the C5 phosphonate (166) to give a mixture of 9Z, 2>E and 9Z 13Z isomers of the ester (393). Treatment of the 9-cis, 13-trans ester with DIBAL and manganese... 

A Ester treatment first with DIBAL and then with [(C2H50)2P(0) CFC02C2H5], B ester added to a solution of [(C2H50)2P(0) CFC02C2H5] and then reduced by DIBAL. Isolated yields are based on R cOOR ... 

The strategy for the construction of 13 from aldehyde 16 with two units of phosphonate 15 is summarized in Scheme 12. As expected, aldehyde 16 condenses smoothly with the anion derived from 15 to give, as the major product, the corresponding E,E,E-tri-ene ester. Reduction of the latter substance to the corresponding primary alcohol with Dibal-H, followed by oxidation with MnC>2, then furnishes aldehyde 60 in 86 % overall yield. Reiteration of this tactic and a simple deprotection step completes the synthesis of the desired intermediate 13 in good overall yield and with excellent stereoselectivity. 

When a cold (-78 °C) solution of the lithium enolate derived from amide 6 is treated successively with a,/ -unsaturated ester 7 and homogeranyl iodide 8, intermediate 9 is produced in 87% yield (see Scheme 2). All of the carbon atoms that will constitute the complex pentacyclic framework of 1 are introduced in this one-pot operation. After some careful experimentation, a three-step reaction sequence was found to be necessary to accomplish the conversion of both the amide and methyl ester functions to aldehyde groups. Thus, a complete reduction of the methyl ester with diisobutylalu-minum hydride (Dibal-H) furnishes hydroxy amide 10 which is then hydrolyzed with potassium hydroxide in aqueous ethanol. After acidification of the saponification mixture, a 1 1 mixture of diastereomeric 5-lactones 11 is obtained in quantitative yield. Under the harsh conditions required to achieve the hydrolysis of the amide in 10, the stereogenic center bearing the benzyloxypropyl side chain epimerized. Nevertheless, this seemingly unfortunate circumstance is ultimately of no consequence because this carbon will eventually become part of the planar azadiene. 

In order to establish the correct absolute stereochemistry in cyclopentanoid 123 (Scheme 10.11), a chirality transfer strategy was employed with aldehyde 117, obtained from (S)-(-)-limonene (Scheme 10.11). A modified procedure for the conversion of (S)-(-)-limonene to cyclopentene 117 (58 % from limonene) was used [58], and aldehyde 117 was reduced with diisobutylaluminium hydride (DIBAL) (quant.) and alkylated to provide tributylstannane ether 118. This compound underwent a Still-Wittig rearrangement upon treatment with n-butyl lithium (n-BuLi) to yield 119 (75 %, two steps) [59]. The extent to which the chirality transfer was successful was deemed quantitative on the basis of conversion of alcohol 119 to its (+)-(9-methyI mande I ic acid ester and subsequent analysis of optical purity. The ozonolysis (70 %) of 119, protection of the free alcohol as the silyl ether (85 %), and reduction of the ketone with DIBAL (quant.) gave alcohol 120. Elimination of the alcohol in 120 with phosphorus oxychloride-pyridine... 

Treatment of the alcohol 211 with f-butyklimethylsilyl triflate and 2,6-lutidine affords disiloxyester 212 with high yield. Reduction of the ester function of 212 with DIBAL followed by Swern oxidation gives the corresponding aldehyde 213, and subsequent alkylation with MeMgBr and Swern oxidation produce methyl ketone 214 (Scheme 7-70). 

Similarly, esters are also reduced to aldehydes with DIBAL-H. 

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