Enol nitro hydrolysis

One effective method for synthesis of tryptophan derivatives involves alkylation of formamido- or acetamido- malonate diesters by gramine[l,2]. Conversion to tryptophans is completed by hydrolysis and decarboxylation. These reactions were discussed in Chapter 12. An enolate of an a-nitro ester is an alternative nucleophile. The products can be converted to tryptophans by rcduction[3,4],... 

Nitroalkenes are also reactive Michael acceptors under Lewis acid-catalyzed conditions. Titanium tetrachloride or stannic tetrachloride can induce addition of silyl enol ethers. The initial adduct is trapped in a cyclic form by trimethylsilylation.316 Hydrolysis of this intermediate regenerates the carbonyl group and also converts the ad-nitro group to a carbonyl.317... 

Hydrolysis of enol esters 0-76 Reduction of halo ketones 0-78 Reduction of hydroxy ketones 0-82 Reduction of diazo ketones or nitro ketones... 

Interestingly, furan ring annelation is also found in the reaction of 3-bromo-4-nitroquinoline with enamines. Due to hydrolysis of the iminium intermediate, the keto group is formed, which after enolization is able to act in the intramolecular cyclization with expulsion of bromide ion (Scheme 17) (76H453). The nucleophilic substitution of hydrogen at C-2 is preferred to that of the nitro group at C-4. 

Conversion into the aldehyde involves hydrolysis of the enol form of the nitro compound. This is rather like the hydrolysis of any imiiie and partiailarly like that of an oxime (Chapter 14). 

Conversion of the nitro compound to the ketone by hydrolysis of the enol derivative is followed J- Froborg and G. Magnusson, J. by an extremely good intramolecular aldol reaction giving the fused five-membered ring. 1978,100, 6728. 

The nitro group can be converted into other useful functional groups following conjugate addition. Reduction gives primary amines while hydrolysis reveals ketones. The hydrolysis is known as the Nef reaction and used to be achieved by formation of the nitro-stabilized anion with a base such as sodium hydroxide followed by hydrolysis with sulfuric acid. These conditions are rather unforgiving for many substrates (and products) so milder methods have been developed. One of these involves ozonolysis of the nitro enolate at low temperature rather than treatment with acid. 

Indole synthesis. In the first step of the synthesis o-nitrotoluene is condensed with diethyl oxalate in the presence of potassium ethoxide, and the product is isolated as the deep purple potassium enolate. Hydrogenation in acetic acid reduces the nitro group and effects cyclization to ethyl indole-2-carboxylate. This on hydrolysis and decarboxylation affords indole. 

Acetal 136 on enolization followed by conjugate addition with nitro olefin 122 gave alkylated products 137 and 138 in a diastereomeric mixture of 10 1. Compound 137 was proceeded for amathaspiramide F synthesis, which on hydrolysis followed by N-trifluoroacetyl protection gave amide 139. Nitro group of compound 139 was converted into oxime 140. Hydrolysis of oxime followed by cyclization and then deprotection of N-trifluoroacetyl group gave amathaspiramide F (134) Scheme 12 [63],... 

Reaction of ethyl crotonate and nitroethane in the presence of the basic 1,8-diaza-bicyclo[5.4.0]undec-7-ene (DBU) led to nitro-ester 3.49 in 74% yield.31 Catalytic hydrogenation of the nitro group and acid hydrolysis produced 3-methyl-4-amino-butanoic acid, 3.50. Choosing different conjugated esters as starting materials led to formation of 3-ethyl- (59% overall yield) 3-propyl- (51% overall yield) 3-isopropyl-(62% overall yield) 3-butyl- (56% overall yield) 3-sec-butyl- (60% overall yield) 3-isobutyl- (58% overall yield) and, 3-r-butyl-4-aminobutanoic acid (31% overall yield).31 The yields observed in this study clearly show that conjugate addition of nitro enolates is a synthetically useful process. 

Similarly, titanium tetrachloride or stannic tetrachloride induces addition of silyl enol ethers to nitroalkenes. The initial product is a complex of the aci tautomer of the nitro group. Hydrolysis of this complex generates the new carbonyl group. ... 

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