Reduction cyano group

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Converting aldehydes and ketones to cyanohydrins is of synthetic value for two reasons (1) a new carbon-carbon bond is formed and (2) the cyano group in the prod uct can be converted to a carboxylic acid function (CO2H) by hydrolysis (to be discussed in Section 19 12) or to an amine of the type CH2NH2 by reduction (to be discussed m Section 22 9)... 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Ketose (Section 25 1) A carbohydrate that contains a ketone carbonyl group in its open chain form Kiliam-Fischer synthesis (Section 25 20) A synthetic method for carbohydrate chain extension The new carbon-carbon bond IS formed by converting an aldose to its cyanohydnn Reduction of the cyano group to an aldehyde function com pletes the synthesis... 

In the study of nuclear reduction of [l,2,3]triazolo[l,5-a]pyridine (99T12881), a number of substituents were also reduced. The cyano group was reduced to give... 

Alkylation of the tetrahydropyridine, 52 (obtained by reaction of a suitable protected derivative of 4-piperidone followed by dehydration and deprotection), with chloroacetonitrile affords 53, Reduction of the cyano group gives the diamine (54). Reaction of this intermediate with the S-methyl ether of thiourea affords guancycline (55). 

Acetyl-5//-dibenz[/>,/]azepine-10-car bon itrile (17, R = CN) when treated with sodium borohydride undergoes reduction (73 % yield) at the CIO - Cl 1 double bond without reduction of the acetyl or cyano groups.212 However, hydroboration of 5-acetyl-5//-dibenz[/y/]azepine (17, R = H) with diborane in tetrahydrofuran under standard conditions is accompanied by reduction of the acyl function to yield 5-ethyi-10,l l-dihydrodibenz[6,/]azepin-10-ol (18).72... 

Enantiopure 3-phenyl-2-cyanoazetidines (S)-238 and (K)-238, which are epimeric at C2, are prepared in high yields from (K)-phenylglycinol. A one-pot sequence, including addition of organohthium or allyhnagne-sium bromide to the cyano group and in situ reduction of the resulting imine with sodium borohydride, allowed for the preparation of 2-(l-aminoalkyl)azetidines, which were then protected as N-Boc derivatives (R,S)-239 and (S,it)-239 [112] (Scheme 36). Complete anti diastereoselectivity (dr more than 95 5 by NMR) was observed in both cases. The same sequence... 

The medicinal chemists subsequently discovered an improved route to racemic acid 9 that started with 2-bromo-2-cyclopente-l-one 11 (Scheme 7.2) [5]. Suzuki-Miyaura cross-coupling of 11 with 4-fluorophenyl boronic acid 12 provided 13 in 67% yield. Conjugate addition of cyanide furnished ketone 14 in 71% yield. Reduction of 14 with NaB H4 gave a 2.8 1 mixture of desired 15 and undesired 16 which were separated by silica gel chromatography. The observed diastereoselec-tivity with the cyano group was similar to ester 6. Hydrolysis of 15 with 5 M NaOH in MeOH gave racemic acid 9 in 91% yield, which was resolved as outlined in Scheme 7.1. 

Reaction of 2-129 with NaCN followed by treatment with NaH and TIPSC1 led to the anthracene 2-130 in 68% yield (Scheme 2.30). The desired lactam 2-131 was then obtained by reduction of the cyano group and ring closure using CoCl2/ NaBH4. Quite recently, this procedure has also been used for a formal total synthesis of tetracenomycin [63]. 

The transformation of the cyano group could also introduce a new chiral center under diastereoselective control (Figure 5.13). Grignard-transimination-reduction sequences have been employed in a synthesis of heterocyclic analogues of ephedrine [81]. The preferential formation of erythro-/3-amino alcohols may be explained by preferential hydride attack on the less-hindered face of the intermediate imine [82], and hydrocyanation of the imine would also appear to proceed via the same type of transition state. In the case of a,/3-unsaturated systems, reduction- transimination-reduction may be followed by protection of the /3-amino alcohol to an oxazolidinone, ozonolysis with oxidative workup, and alkali hydrolysis to give a-hydroxy-/3-amino acids [83]. This method has been successfully employed in the synthesis L-threo-sphingosine [84]. 

The reduction of nitroarenes to azoxy compounds ArN=N(0)Ar is promoted by bismuth trichloride/powdered zinc427. Aromatic amines are formed in excellent yields in the reduction of nitroarenes with BH3/NiCl2428 or nickel boride429. Acyl, ester, amide and cyano groups are not affected. Reaction of the nitro compounds RCH2N02 (R = Ph, Bz... 

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