Reduction, of amides

When carried out under standard conditions with Et3SiH/TFA, reduction of acrolein leads to a mixture of allyl alcohol, 1-propanol, and di-n-propyl ether in addition to allyl trifluoroacetate and -propyl trifluoroacetate.434 The 1,2-reduction of cinnamaldehyde with triethoxysilane in the presence of fluoride ion provides the corresponding allyl alcohol in good yields (Eq. 261). 

Diphenylsilane catalyzed by various salts promotes the 1,2-reduction of cinnamaldehyde.318 Cesium fluoride catalysis is particularly effective.320 It is possible to stop these reactions at the silyl ether stage.73,320 The 1,2-reduction of citral is accomplished in high yield with diphenylsilane and Wilkinson s catalyst (Eq. 262) 435 Interestingly, the trialkylsilanes, ethyldimethylsilane and triethylsilane, give high yields of the 1,4-reduction product whereas diisopropylsilane gives a 1 1 mixture of 1,2- and 1,4-reduction (Eq. 263)435 

4-reduction of a,/3-unsaturated aldehydes is best carried out with diphenylsilane in the presence of zinc chloride and tetrakis(triphenylphosphine) palladium436 or a combination of triethylsilane and tris(triphenylphosphine) chlororhodium 437 Other practical approaches use phenylsilane with nickel (0) and triphenylphosphine438 and diphenylsilane with cesium fluoride.83 It is possible to isolate the initial silyl enol ether intermediate from the 1,4-hydrosilylation of o, /3-unsaturated aldehydes (Eq. 264).73,411 The silyl enol ethers are produced as a mixture of E and Z isomers. 

2-hydrosilylation of a,/3-unsaturated ketones is possible and provides a convenient route to allyl alcohols. The standard conditions of Et3SiH/TFA lead to overreduction to the saturated alcohol with mesityl oxide 434,439 The combination of EtsSiH/AlCE/HCl with mesityl oxide gives a mixture of the 1,2-reduction product 4-methylbut-3-ene-2-ol and the fully reduced product, 2-methylpent-2-ene.136 The Ph2SiH2/RhH(PPh3)4 reduction of cyclohexenone gives reaction at 

The triethylsilane reduction of the alkylidene-l,3-dione 78 occurs fashion at the acyclic carbonyl group (Eq. 267).396 in a 1,2- 

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R4N= BnEtsN or BU4N Heterocylces 1980, 14, 1437, 1441 reduction of amides to amines reduction of nitriles to amines... 

Aldehydes are more generally prepared by electrolytic reduction of amides, the reduction of carboxylic adds being possible only when they are activated by a strongly electron-withdrawing group (58). 

The preparation of amines by the methods described m this section involves the prior synthesis and isolation of some reducible material that has a carbon-nitrogen bond an azide a nitrile a nitro substituted arene or an amide The following section describes a method that combines the two steps of carbon-nitrogen bond formation and reduction into a single operation Like the reduction of amides it offers the possibility of prepar mg primary secondary or tertiary amines by proper choice of starting materials... 

Reduction of amides (Section 22 9) Lithi um aluminum hydride reduces the car bonyl group of an amide to a methylene group Primary secondary or tertiary amines may be prepared by proper choice of the starting amide R and R may be ei ther alkyl or aryl... 

In general, reduction of amides to alcohols is difficult. More commonly the amide is reduced to an amine. An exception uses LiH2NBH3 to give the alcohol. Reduction with sodium metal in propanol also gives the alcohol.Acyl imidazoles are also reduced to the corresponding alcohol with NaBH4 in aqueous HC1. °... 

Answer Disconnection oi the amide reveals secondary amine (4). This can be distonnected in various ways using reduction of amides (benzyl side only) or imides (either side). Again the order doesn t matter. 

Scheme 46 Fe-catalyzed reduction of amides to amines under either thermal or photoassisted conditions...

Scheme 47 Fe-catalyzed hydrosilane reduction of amides to amines...

Reduction of amides by LiAlH4 is an important method for the synthesis of amines. 

Diborane permits the selective reduction of amides in the presence of ester and nitro groups. 

Reduction of amides 159 with LiAlH4 provides tetrahydropyrazines 160 <2004ARK286>. Further reduction of protected 160 (R1 = Cl, Rz = Me, R3 = BOC, X = C, Y = N) with NaCNBH3 furnishes compound 161 as a mixture of isomers in an 8 1 ratio (Scheme 2) <2006BML1207>. 

Supplemental References for Table 13. Organosilane Reduction of Amides... 

This method is also applicable to the reduction of amides to the corresponding aldehydes and alcohols by controlling the amount of t-BuOH and supplied electricity. The reduction in the presence of t-BuOD gives deuterated aldehydes (Scheme 17). 

Scheme 17 Cathodic reduction of amides to alcohols and aldehydes yields (alcohol) 70-82%, yields (aldehyde) 65%.

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