Diisobutylaluminum hydride amides

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

Amides can also be deacylated by partial reduction. If the reduction proceeds only to the carbinolamine stage, hydrolysis can liberate the deprotected amine. Trichloroac-etamides are readily cleaved by sodium borohydride in alcohols by this mechanism.237 Benzamides, and probably other simple amides, can be removed by careful partial reduction with diisobutylaluminum hydride (see Section 5.3.1.1).238... 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

Furthermore other functionalities instead of an alcohol can be introduced in this step. In the presence of imidazole and a hydroxylamine salt a transformation into the Weinreb amide 32 takes place. Also the oxazolidinethione can be directly reduced to the aldehyde with diisobutylaluminum hydride (DIBAH). 

Attempted formation of the benzyl ether of ( f-ethyl lactate with NaH/BnBr results in considerable racemization (50-75 % ee). This racemization is obviated by use of the amide analog noted in eq 2. Diisobutylaluminum Hydride has been used to convert the ester directly to the aldehyde employing the methoxymethyl, benzyl, ... 

Just as considerable effort has been exerted to utilize LiAlH4 or its derivatives for the selective reduction of amides to aldehydes, so too has much exertion gone into the use of diisobutylaluminum hydride. This area has been reviewed. " With DIBAH itself in diethyl ether at 0 °C, A -methylanilides furnish aldehydes in yields of 25-70%, the remainder of the reaction products being mostly amines. The yield of aldehyde drops severely above 0 °C. DIBAH, tempered by the addition of various amines, has been discussed in Section 1.11.2 (ref. 5) and Section 1.11.4 (ref. 60). One of these reagents, bis(4-methyl-l-piperazinyl)aluminum hydride has been recommended for the reduction of dimethylamides (and other amides) to aldehydes in 65-80% yield." The hydride is mild enough for it to be necessary to reflux the amide in diethyl ether with the reagent for several hours. It should be noted that under such conditions acids and esters will be reduced also. 

Treatment of /V,D-dimethyIhydroxyIamine with acid chlorides gives the amides (32 Scheme 14) which with lithium aluminum hydride at -78 °C or diisobutylaluminum hydride at 0 °C give aldehydes in about 70% yield. ... 

Cyclopropanation of a,jS-unsaturated AT-methoxy-AT-methylamides 5 with dimethyloxo-sulfonium methanide afforded the cyclopropanecarboxamides 6 in yields far superior to those obtained with the corresponding a,/J-unsaturated ketones. In almost all cases, the trans-isomer was exclusively obtained in analogy to the cyclopropanation of the corresponding unsaturated ketones. The oxygen atom of the methoxy group on the A -methoxy-A -methyl-amide 5 was found to facilitate the reaction. The substituted amides 6 can be converted to ketones (methylmagnesium bromide), aldehydes (diisobutylaluminum hydride) and carboxylic acids (potassium rerf-butoxide/water). It is noteworthy that cyclopropanecarbaldehydes and -carboxylic acids, which are not directly accessible from the corresponding a,)8-unsaturated systems under standard cyclopropanation reactions, can be obtained indirectly by this method. 

There are many methods for the cleavage of 4,5-dihydrooxazoles once they have served their purpose. An effective method for hydrolyzing them back to carboxylic acids employs trifluoro-methanesulfonic anhydride <92SC13>. Intermediate ring-opened esters (100) are A(-methylated, then saponified to the acids (Scheme 34). The oxazoles may also be converted into aldehydes or nitriles. In a one-pot, two-step procedure, 4,5-dihydrooxazoles are transformed into alcohols (101) <93TIj4893>. Chloromethyl methyl ether converts the dihydrooxazoles into ring-opened amides in the first step, and these are reduced with diisobutylaluminum hydride (Scheme 35). 

Since a synthetic route to heterocyclic calcitriol derivatives was still lacking, explorative research had to be carried out. The vitamin D aldehyde 1 was prepared according to the Leo protocol [192] followed by a photosensitized isomerization of the triene unit in seven steps (Scheme 10.2). Wittig-Horner olefination selectively yielded the E-double bond configuration of the Weinreb amide 2. Reduction with diisobutylaluminum hydride gave the unsaturated aldehyde 3 without any evidence for overreduction. This aldehyde could serve as a valuable intermediate for further elaboration of the side-chain [194],... 

In contrast to these methods the amide precursors for the macrocyclic ligands 73 and 74 (e.g., 72) are reduced with diisobutylaluminum hydride (DIBAL-H),... 

Pd2(dba)3/Ph3P as the catalyst, and obtained an 80% yield of bipyridyl 54 (Scheme 15). Conversion of the amide of 54 to the oxime was accomplished in two steps in 44% overall yield by reduction of the amide to the aldehyde with diisobutylaluminum hydride to provide 55 followed by condensation with hydroxylamine. Material prepared in this way... 

The dialkylboranes and dialkylaluminums are also of value when partial reduction of an ester or amide is desired. The intermediates formed by the first hydride transfer are stable under the conditions of the reduction. Subsequent hydrolysis then provides the carbonyl compound at the aldehyde reduction stage. This method using diisobutylaluminum hydride has been particularly useful for reduction of esters to... 

Under some circumstances, it is possible to effect removal of amide groups by selective hydride reduction. Trichloroacetamides are readily cleaved by sodium borohydride in alcohols. Another reductive method that can be applied to ben-zamides, and probably to other simple amides, involves treatment with diisobutylaluminum hydride. At low temperatures, this reduction stops at the carbinolamine stage. Hydrolysis then yields the amine. 

Diisobutylaluminum hydride Aldehydes from carboxylic add amides s. 16,98... 

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