Amines reductions, diisobutylaluminum hydride

The reductive Beckmann rearrangement of oximes has been effected with several types of aluminum hydride reagents. Early examples exhibited only moderate regioselectivity, giving mixtures of primary amines and rearranged secondary amines. Recently, diisobutylaluminum hydride was reported to be most satisfactory for this type of transformation (equation 20). Here dichloromethane is the solvent of choice, and attempted use of ethereal solvents results in the formation of a mixture of primary and secondary amines. ... 

The milder metal hydnde reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodexnins reduce ketones to opucally active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc bromide-MMA. A -tetra-methylethylenediamme (TMEDA) reduces a,a-difluoro-[i-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The three isomers are formed on reduction with aluminum isopropoxide... 

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... 

A stereoselective total synthesis of ( )-hirsutine has been developed by Brown et al. (179). Catalytic hydrogenation of hydroxycyclopentenone 327, prepared previously (180), afforded a mixture of isomeric diols 328, which were quantitatively cleaved by sodium periodate to supply 329. Reductive amination of 329 with tryptamine resulted in tetrahydropyridine 330, which upon treatment with aqueous methanol in the presence of hydrochloric acid gave indolo-[2,3-a]quinolizine 321 with pseudo stereochemistry. Conversion of 321 to ( )-hirsutine was accomplished in a similar manner by Wenkert et al. (161) via selective reduction with diisobutylaluminum hydride and methylation with methanol (179). 

Asymmetric reduction of (5s)-sulfmimine 110 with diisobutylaluminum hydride (DIBAL) afforded a diastereomeric mixture of sulfinamides 111 in 92% yield and in a ratio of 96 4.34 Use of sodium boron hydride, lithium aluminum hydride, or lithium alkoxyaluminum hydride resulted in lower optical yields.33,34,75 The sul-finyl group can be removed by treating 111 with trifluoroacetic acid (TFA) and methanol to give a-phenylethyl amine (112). 

REDUCTION, REAGENTS Bis(N-methylpi-perazinyl)aluminum hydride. Borane-Di-methyl sulfide. Borane-Tetrahydrofurane. Borane-Pyridine. n-Butyllithium-Diisobu-tylaluminum hydride. Calcium-Amines. Diisobutylaluminum hydride. 8-Hydroxy-quinolinedihydroboronite. Lithium aluminum hydride. Lithium 9-boratabicy-clo[3.3.1]nonane. Lithium n-butyldiisopro-pylaluminum hydride. Lithium tri-j c-butylborohydride. Lithium triethylborohy-dride. Monochloroalane. Nickel boride. 2-Phenylbenzothiazoline. Potassium 9-(2,3-dimethyl-2-butoxy)-9-boratabicy-clo[3.3.1]nonane. Raney nickel. Sodium bis(2-methoxyethoxy)aluminum hydride. Sodium borohydride. Sodium borohy-dride-Nickel chloride. Sodium borohy-dride-Praeseodymium chloride. So-dium(dimethylamino)borohydride. Sodium hydrogen telluride. Thexyl chloroborane-Dimethyl sulfide. Tri-n-butylphosphine-Diphenyl disulfide. Tri-n-butyltin hydride. Zinc-l,2-Dibromoethane. Zinc borohydride. 

Oxime — imine. The low valent titanium reagent prepared from TiClj and diisobutylaluminum hydride (1 3) in THF reduces the oxime 1 to the very labile imine 2. Reduction of 2 to the corresponding amine with diisobutylaluminum... 

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. 

With few exceptions, organometalUcs add only once to nitriles (Section 8.6.4). Only if there is a very strong Lewis acid present to activate the anionic intermediate of the first nucleophilic attack will a second addition take place. An example of this second addition is the reduction of nitriles with LiAlH4, which proceeds all the way to the amine (Section 8.6.3). The AIH3 formed from the initial reduction acts as a Lewis acid to catalyze the second addition. This second addition can be prevented by using one equivalent of a less reactive aluminum hydride like LiAlH(OEt)3 or diisobutylaluminum hydride, [(CH3)2CHCH2l2AlH. The reactions in the acidic water workup are the reverse of imine formation (Section 10.5.2). 

Diisobutylaluminum hydride. 13, 115-116 15, 137-138 16, 134-135 17, 123-125 Monosilyl acetals and amines. The DIBALH reduction products of esters can be converted into monosilyl acetals by treatment with TMSOTf-pyridine and those of nitriles into amines by the addition of organolithium reagents. ... 

While most reducing agents lead to the expected bornylamines as products of the reduction of camphor oxime (see above), diisobutylaluminum hydride is a notable exception, as a ring-enlarged amine, (1/ ,47 )-1.8,8-trimethyl-2-azabicyclo[3.2.1]octane (67) is obtained in high yield when starting with the oxime of (+ )-camphor16, It has been used as the lithium salt in enantioselective deprotonation and elimination reactions (Section C.). 

N-Sitylimine 89 in ether at -78°C was asymmetrically alkylated with butyl-Uthium in the presence of the diUthium alkoxide of the chiral diol 93 (76%, 62% ee) (Scheme 27) [76]. Addition of the preformed (-)-sparteine (19)-BuLi complex to benzaldehyde N-diisobutylaluminoimine 90, prepared in situ from partial reduction of benzonitrile with diisobutylaluminum hydride, in pentane at -78°C gave the primary amine 92 in good ee (70% yield, 74% ee) [77]. The use of polymer-supported amino alcohol 94 in THF at -78°C allows the asymmetric alkylation of an M-borylimine 91 to give the primary amine 92 with 44% ee [77]. 

Whereas monoazacycloalkanes are generally prepared by reduction of the corresponding lactams with LiAIH4, somewhat different reactions for their synthesis have also been described. The reduction of the cyclic oxime (26) with diisobutylaluminum hydride (dibal-H) gives the cyclic amine (27) in 70% yield (Equation (4)) <83TL4711>. 

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. 

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]

In Summary Carboxylic amides are named as alkanamides or as lactams if they are cyclic. They can be hydrolyzed to carboxylic acids by acid or base and reduced to amines by lithium aluminum hydride. Reduction by bis(2-methylpropyl)aluminum hydride (diisobutylaluminum hydride) stops at the aldehyde stage. 

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