Imino lactones

Other nucleophilic functional groups can participate in iodocyclization. Amides usually react at oxygen, generating imino lactones that are hydrolyzed to lactones.88... 

In order to decrease the number of chemical steps in the synthesis of l-[4- F]fluorophenylalanine, a potential marker for probing protein synthesis [140a], [4- F]fluorobenzaldehyde has been directly condensed with an imino-lactone. Hydrolysis then chiral HPLC yield the S amino acid in 5 % radiochemical yield (Scheme 33). 

Brown and Edwards have studied the photochemical reaction of ethyl azidoformate with dihydropyran and have isolated in good yield the very reactive aziridine 115. The thermal reaction between the two compounds, however, takes a completely different course via triazoline to imino lactone. 

It is not known whether the cyclization of hexose derivatives takes place with the C4- or the C5-hydroxyl group work on model compounds suggests that both the furanoid and the pyranoid rings are possible. Imino-lactone formation is theoretically possible for any 4- or 5-hydroxy nitrile,... 

Isocyanides react with epoxides in the presence of gallium(lll) chloride to form 0 ,/3-unsaturated a-amino imino-lactones <20030L4991>. Oxazolidinones are formed on solid phase by the reaction between epoxides and isocyanates <2003JC0789>. 

Fschenmoser et at. have described two useful reactions of these addition products for synthesis. Thus (2) can be converted efficiently into a y-lactone. Treatment of the mixture of epimeric nitriles (2) with I.I molar eq. of potassium r-butoxide in /-butanol at 80° under nitrogen gives the imino lactone (4) in 85 % yield. This on acid hydrolysis is converted into the y-lactonc (5) in 82% yield. The two isomers (Sa, SP) are separable by gas chromatography. 

In view of these many precedents it is surprising that the intramolecular displacement of the sulfur function of methionine derivatives has not been utilized for selective cleavage of methionine peptides. The method has only recently been applied to a number of methionine peptides which according to the following scheme (CXX-CXXIII) were first converted to sulfonium salts and then subjected to intramolecular (imino) lactonization and hydrolysis by short heating in water (Lawson et al., 1961). Table XV shows the strong influence of the nature of the added alkyl group on the yield in... 

The intramolecular participation of the C-peptide group in the imino-lactonization reaction of tryptophan peptides requires a certain freedom... 

Imino lactones, such as (22), can be reduced cleanly to the morpholinone (23) in an aptotic medium using diethyl malonate as a mild proton donor (equation 9). The electroreductive behavior of this class of activated imines is presently under study. 

The highly electron-deficient l,2,4-triazoline-3,5-diones 200 21 122 readily attack the 3-position of ethyl 2-amino-4,5-dihydrofuran-3-carboxylates (8, X = O, n = 1) at room temperature to give the imino lactone adducts... 

Attempted reaction of (52), (53), or the 5a-5,6,22,23-tetrahydro-derivative with methoxymethylenetriphenylphosphorane was unsuccessful, although pregnenolone acetate, or better its tetrahydropyranyl ether, afforded the vinyl ether, as (59). Wittig reaction of either the 5a- or A -diacetates (60) or (61) with the anion of diethylcyanomethylphosphonate gave good yields of unsaturated nitrile (62) in the absence of an acidic work-up, or the imino-lactone hydrochloride (63) in the presence of acid, which could be converted in good yield to the butenolide (64). 

On treatment with nitrous acid, cephalosporin C yields the imino lactone 7. Its C=N bond is more reactive than the P-lactam ring and favours the hydrolytic formation of 8 in good yioid. 

Isocyanides readily undergo cycloaddition reactions, and these are very valuable in the formation of heterocyclic rings. Reaction of j5-nitrostyrene with an alkyl isocyanide gives a hydroxy indole (146). Reaction proceeds even more readily between tosylmethyl isocyanide (147), in which the methylene is activated, and aryldiazonium compounds. With ketenes, isocyanides give imino lactones. However, with r-butylcyanoketene, the reaction follows a different pathway involving the carbonyl bond of the ketene, to yield 148. A [1 + 3] cycloaddition of an isocyanide to a 1,3-dipole has been used to prepare azetidines. The method has been used for synthesis of a number of azetidines . 

Very closely related are two procedures that result in formation of y-lactones. In one procedure, amides are converted to iV-iodoamides by reaction with iodine and f-butyl hypochlorite. Photolysis of the N-iodoamides gives lactones via imino lactone intermediates ... 

In the coupling of monosaccharide 1,4-lactones to benzidine-substituted agarose, it is not known whether an imino-lactone [e.g. (4)] or an amide e.g. (5)] is formed. ... 

Although nitronate 36 remains an elusive goal we were able to apply the same strategy to synthesis of the hydrox-imino lactones 39. These materials are initially produced as a mixture of the and JE isomers however, they isomerize to the more stable E form fairly rapidly on standing. 

A 0.38 N soln. of Ag-tetrafluoroborate in methylene chloride-benzene added dropwise at —20 with agitation to a soln. of ( + )-Na-(y-chlorobutyryl)-L-tryptophan methyl ester in abs. methylene chloride, kept 1 hr. at —20 , agitated 1 hr. at 0°, after an additional 1.5 hrs. at room temp, excess Ag-tetrafluoroborate decomposed with triethylamine hydrochloride, the resulting crude imino-lactone dissolved in acetonitrile treated with methyl iodide, stored 41 hrs. at 30 , excess methyl iodide and 2/3 of the acetonitrile evaporated in vacuo at room temp., the residual soln. allowed to stand 2 hrs. at 20 with 2 N KHGO3-soln., and the product isolated as the hydrochloride (+)-Ngj-methyl-L-trypto-phan methyl ester hydrochloride. Y 84.5%. H. Peter et al., Helv. 46, 577 (1963). 

Unsaturated ketones and aldehydes reacted with arylisonitrile in the presence of a GaCls catalyst giving imino lactones (Scheme 7.23) [45]. The reaction was triggered by the carbonyl activation with the Lewis acid. Although the use of stoichiometric Et2AlCl was previously reported for this transformation, GaCla could be recycled. Acetals also reacted with isonitrile giving the insertion products (Scheme 7.24) [46]. 

Intramolecular substitutions mediated by Ag" " do not seem to require activated halides. For example, w-chloro amides react with AgBF4, giving products from intramolecular attack of the amide oxygen. Depending on the structure of the amide, imino lactones, imino lactonium salts, or lactone hydrazones (eq 4)" are obtained as products. Huorination of a-bromo ketones using AgBp4 has also been reported. ... 

---