Reduction with ammonium formates

The intramolecular palladium catalyzed ring closure of the tetrahydro-isoquinoline derivative depicted in 8.41. led to the formation of the aporphine derivative in good yield, which was then converted into racemic aporphine in three steps. In the ring closing step 20 mol% palladium acetate and 40 mol% tricyclohexylphosphine were used as catalyst. The removal of the hydroxyl group was also achieved by palladium catalysis through its conversion to triflate and the subsequent reduction with ammonium formate in the presence of palladium acetate and dppf.53... 

Kemmerer.1 On the other hand, Keller and Smith, who consider that traces of palladium are lost by this method, determined the palladium content of the compound electrolytically, as also did Amberg 2 in two series of experiments, and Woernle. Moreover, Amberg made a series of determinations in which the reduction to metal was accomplished in solution with hydrazine sulphate, while Shinn 3 effected his reductions with ammonium formate. The results of these investigations are summarised in the following table ... 

Catalyzed reductions with ammonium formate proceed with retention of configuration, at least for the case of nitro compounds. Treatment of steroid derivative (12) with ammonium formate in methanolic solution and a catalytic amount of palladium on charcoal gave exclusively amino steroid (13), as shown in equation (13). A similar technique has been used to produce members of the ephedrine family. 

Intramolecular Reactions of Alkynes with Carboxylic Acids, Alcohols, and Amines. Addition of carboxylic acids, alcohols, and amines to alkynes via oxypaUadation and aminopallada-tion proceeds with catalysis by Pd salts. Intramolecular additions are particularly facile. Unsaturated y-lactones are obtained by the treatment of 3-alkynoic acid and 4-alkynoic acid with Pd(PhCN)2Cl2 in THF in the presence of Et3N (eq 54), and -lactones are obtained from5-alkynoic acids. 5-Hydroxyalkynes are converted to the cyclic enol ethers (eq 55). The oxypalla-dation is a irons addition. Thus stereoselective enol ether formation by reaction of the alkynoic alcohol with Pd(PhCN)2Cl2, followed by reduction with ammonium formate, has been applied to the synthesis of prostacyclin (eq 56). Intramolecular addition of amines affords cyclic imines. 3-Alkynylamines are cyclized to 1-pyrrolines while 5-alkynylamines are converted to 2,3,4,5-tetrahydropyridines (eq 57). ... 

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

Formic acid is a good reducing agent in the presence of Pd on carbon as a catalyst. Aromatic nitro compounds are reduced to aniline with formic acid[100]. Selective reduction of one nitro group in 2,4-dinitrotoluene (112) with triethylammonium formate is possible[101]. o-Nitroacetophenone (113) is first reduced to o-aminoacetophenone, then to o-ethylaniline when an excess of formate is used[102]. Ammonium and potassium formate are also used for the reduction of aliphatic and aromatic nitro compounds. Pd on carbon is a good catalyst[103,104]. NaBH4 is also used for the Pd-catalyzed reduction of nitro compounds 105]. However, the ,/)-unsaturated nitroalkene 114 is partially reduced to the oxime 115 with ammonium formate[106]... 

Diphenylisoinclole (29) can be prepared by a modified Leuckart reaction of o-dibenzoylbenzene (46), using an ammonium salt of formic acid the process is essentially a reductive alkylation of ammonia, accompanied by cyclization, and leads to 29 in 44% yield with ammonium formate, and 47 in 28% yield with methylammonium formate. 1,3-Diphenylisoindole. (29) can also be obtained in good yield by the reaction of 46 with 1,1-dimethylhydrazine. ... 

The reduction of y-nitroketone acetals as in Eq. 6.50 with ammonium formate in the presence of Pd/C gives the corresponding amines in good yields. However, the reduction of y-nitro ketones are reduced to cyclic nitrones (Eq. 6.51).97 This reduction is far superior to the classical method using Zn/NH4C1 due to improved yield and simple workup. 

The reduction of P-nitro alcohols with ammonium formate in the presence of Pd/C also proceeds with retention of their configurations (Eq. 6.52).98... 

Reaction of phenyl vinyl ketone with cyclopentanone under thermal conditions resulted in a diastereomeric mixture of 1,5,9-triketones 374 via a double Michael reaction. Treatment of this mixture with ammonium formate in polyethyleneglycol-200 under microwave irradiation conditions led to the very fast and efficient formation of a 2 1 diastereomeric mixture of cyclopental flquinolizidines 375 and 376 <2002T2189>. When this reductive amination-cyclization procedure was carried out starting from the purified /ra r-isomer of 374, the result was identical to that obtained from the cis-trans mixture, showing the operation of thermodynamic control (Scheme 86). 

Amino-l,2,4-triazole was alkylated with 4-nitrobenzyl bromide by simply refluxing the mixture in isopropanol to give SO in excellent yield. The aminotriazole SO was deaminated with NaNOa in aqueous HCI and the nitro group was reduced with ammonium formate catalyzed by 10% Pd/C to deliver 47 in an improved yield over the route shown in Scheme 17. Diazotization of 47, reduction of the diazonium salt with sodium sulphite and Fischer indolization of the resulting hydrazine with 4-( /, /-dimethylamino)butanol dimethyl acetal was performed in a single step to afford rizatriptan (4) in 45% yield. 

Formation of the imine and subsequent reduction can often be achieved in one pot . Thus, a microwave-assisted reductive amination-cyclisation domino reaction was used as the key step in the synthesis of perhydrocyclo-penta[ij]quinolizines from 1,5,9-triketones. This type of heterocycle is an important structural element in a series of alkaloids. The reaction of the triketone with ammonium formate in PEG-200 was performed within 1 min using microwave irradiation of370 W in a domestic microwave oven. Amixture oftwo ofthree possible stereoisomers was obtained in 87% overall yield (Scheme 4.29)52. 

The Leuckart reductive animation of carbonyl compounds with ammonium formate or formamide was found to benefit strongly, when the reaction was carried out under solvent free conditions with microwave irradiation. Yields of N-alkylated formamides of up to 97% were produced in reaction times of about 30 min, as compared to thermal... 

Durst and Sharma [86] have reported the stereospecific synthesis of 3-spiro-epoxyazetidin-2-ones 55 (Scheme 14). The oxidation of the diastereoisomers of compound 52 with PCC provided a single acetyl compound 3-acetyl-3-benzyloxy-azetidin-2-one 53. Nonchelation controlled L-Selectride reduction of 53 gave the isomerically pure 3-hydroxyethylazetidin-2-one as the sole reduced product, which was further converted to tosylate 54 using NaH/tosylimidazole. The debenzylation-oxirane formation sequence was conveniently performed as a single pot operation with ammonium formate, 5% Pd/C in refluxing methanol as the hydrogen transfer reagent combination. 

Clemmensen-type reduction.1 Aromatic ketones can be reduced to the corresponding methylene compounds with ammonium formate on transfer hydrogenation in acetic acid catalyzed by 10% Pd/C. The reduction is usually complete in 10-30 minutes at 110°. Halo and nitro substituents can be reduced under these conditions, and a,p-unsaturated carbonyl groups are reduced to saturated carbonyl groups. 

While in propargylic systems a vinylogous reduction is the normal reactivity, in allylic systems a double bond shift on reduction is realized more generally only when terminal alkenes are produced. Especially Interesting in this respect is the Pd-catalyzed hydrogenolysis of allylic acetates (X = OAc) with ammonium formate (equation 45). ... 

Reduction The stable Ni(0) complex is a useful catalyst for reduction of carbonyl compounds (to alcohols), sulfonyl azides (to sulfonamides), imines and nitro compounds (to amines) with ammonium formate. 

Formation of a cyanoformamidine by treatment of a symmetrical diphenylthiourea with potassium cyanide in alcohol containing lead carbonate, reduction with ammonium sulfide, and ring closure with concentrated sulfuric acid to isatin-2-anil also formed smoothly by ring closure of the cyanoformamidine with aluminum chloride in benzene or carbon disulfide. 

In an analogous manner, novel 2-(2-hydroxyaryl)quinolines can be prepared via a one-pot synthesis from intramolecular reductive coupling reactions of 2 -hydroxy-2-nitro-chalcones [75]. Accordingly, 2 -hydroxy-2-nitrochalcones 177a-b were treated with ammonium formate and Pd/C at room temperature to give a mixture of 2-(2-hydroxy-aryl)quinolines 178a-b and 2-(2-hydroxyaryl)quinoline-N-oxides 179a-b. 

The reductive animation of 3-oxo-l,2.3.4-tetrahydrocarbazole with (S)-phenylethylamine and sodium borohydride leads to (37 )-3-[(l.S )-phenylethylamino]-l,2,3,4-tetrahydrocarbazole in 39.7% yield. The cleavage of the phenylethyl group is accomplished by a transfer hydrogenation, with ammonium formate as a hydrogen donor and palladium on charcoal as a catalyst, to give the enantiomerically pure (3/ )-3-amino-l,2,3,4-tetrahydrocarbazole23. 

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