Reduction of a Nitrile to an Aldehyde

Stephen reduction The reduction of a nitrile to an aldehyde using HC1, followed by anhydrous SnCl2, which produces the intermediate imine, which is then hydrolysed. 

Reduction of an Acyl Chloride to an Aldehyde 727 Reduction of an Ester to an Aldehyde 728 Reduction of a Nitrile to an Aldehyde 728... 

Nitriles [1, 725-726, after citation of ref. 23]. The original method of Backeberg and Staskun23 for conversion of a nitrile to an aldehyde does not proceed well with hindered nitriles in this case, use of moist Raney nickel in formic acid is recommended.233 The formic acid serves as a source of hydrogen, and the nickel catalyzes both decomposition of the acid and reduction of the nitrile. 

The reaction is similar to the l>II Ail reduction of a nitrile to yield an aldehyde, except that the attacking nucleophile is a carbanion (R ) rather than a hydride ion. For example ... 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

The complex hydride reductions of nitriles to aldehydes compare favorably with the classical Stephen reduction which consists of treatment of a nitrile with anhydrous stannous chloride and gaseous hydrogen chloride in ether or diethylene glycol and applies to both aliphatic and aromatic nitriles [183,285, 1152]. An advantage of the Stephen method is its applicability to polyfunctional compounds containing reducible groups such as carbonyl that is reduced by hydrides but not by stannous chloride [1153]. 

Functional Group Transformations Functional group transformations help us in the conversion of a functional group to an aldehyde or a ketone without affecting the carbon skeleton of the molecule. Aldehydes can be synthesised by the oxidation of primary alcohols, or by the reduction of esters, acid chlorides, or nitriles. Since nitriles can be obtained from alkyl halides, this a way of adding an aldehyde unit (CHO) to an alkyl halide ... 

You can now clearly see the similarity with our target molecule , grandisol, but there are several more steps to carryout yet. The nitrile needs to be got rid of completely—we showed you a few ways of getting rid of fimctional groups in the last chapter, and the one used here was the Wolif-Kishner reduction of an aldehyde. The aldehyde comes from reduction of the nitrile with DIBAL. 

Hydride abstraction from dienyl tricarbonyl iron complexes furnishes cationic dienyl tricarbonyl iron complexes. For example, reaction of the diene-iron tricarbonyl complex (115) with triphenyhnethyl hexafluorophosphate followed by trimethylsilyl cyanide furnished with excellent regio- and stereoselectivity a new diene iron tricarbonyl complex (116) (Scheme 170). Excellent regio- and stereoselectivity is seen upon reaction of the cationic complex (116) with trimethylsilyl cyanide (TMS-CN) (Scheme 170). Reduction of the nitrile affords a spirocyclic lactam complex. Intramolecular cyclization of in situ formed enols furnishes spirocyclic compounds again with excellent stereoconfrol (Scheme 171). An interesting example of hydride transfer from a cyclohexadiene ring to a pendant aldehyde followed by nucleophilic addition is seen in Scheme 172. 

Reduction of an aryl halide at a cadmium-modified nickel cathode in DMF containing TBABF4 leads to a formylation reaction between aryl carbanions and the solvent [186]. Two papers [187,188] have appeared in which reduction of aryl halides gives an aryl carbanion, which, by acting as a base to deprotonate a suitable nitrile, can cause coupling of the nitrile with esters, aldehydes, and ketones. Electrochemical trimethylsilylation of aryl halides can be effected at a stainless-steel or carbon-cloth cathode in THF-HMPA containing TEABF4 and trimethylchlorosilane [189]. 

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