A2-Pyrrolines

Arylidene alkylamines and diphenyl cyclopropenone gave rise to products 397-399, whose formation can be interpreted by means of oxidative secondary reactions of the 5 H-A2-pyrrolin-4-one 396 (R2 = H) initially generated252. ... 

Methylmercapto-N-methyl-A2-pyrroline has been prepared by the present method only.11,12... 

METHYLMERCAPTO-N-METHYL-A2-PYRROLINE (2-Pyrroline, l-methyl-2-methylthio-)... 

Conversion of esters of acylated aminoisobutyryl malonic acids into 3-oxo-A2-pyrrolines [182-183],... 

Conversion of isoxazolium salts by the action of alkali cyanides into 4,5-dioxo-A2-pyrrolines [184, 185]. 

The gross structural features, presence of a tetramic acid and E-decenoyl side chain, could be inferred from NMR studies. Methanolysis (HCl/MeOH) of 47 and pentane extraction of the quenched reaction mixture gave two compounds that were determined to be the methyl esters of decenoic acid and N-(2-decenoyl)leucine. The nature of the 3-acyl tetramic acid was deduced from the identification of 48 and 49 in the aqueous portion of the methanolysis reaction mixture following treatment with trifluoroacetic acid anhydride. The unusual C-C bond fragmentation under acidic conditions, and the structure of the antibiotic was confirmed by synthesis of racemic 47 [86]. The configuration at the lone chiral centre was established as R by chiral GC. The carbon NMR spectrum of 47 indicated an equilibrium between three tautomers in which the A2-pyrrolin-4-one form is preferred (60%) and the two internal tautomers (50, 51) make equal contributions (20% each). 

The reduction of pyrroles by zinc in acetic acid or hydrochloric acid gives, initially, as the major product, A-pyrroline, together with A1- and A2-pyrrolines, all of which are further reduced to pyrrolidine (Scheme 54) (B-77MI30507). Reduction of 2,5-disubstituted pyrroles produces both the cis- and the trans- A3-pyrrolines, (206) and (207). 

A3-Pyrrolines are obtained, as the major product, by the reduction of pyrroles by zinc in hydrochloric acid via the initial protonation of the ring at the 2-position. The minor products are the A1- and A2-isomers, which result from the reduction of the 3-protonated species. As shown in Scheme 54 (Section 3.05.1.5), there is a tautomeric equilibrium between the A1- and A2-pyrrolines, which is catalyzed by the acidic medium, but there is no evidence of a tautomeric equilibrium between these isomers and the A3-pyrrolines. The tautomeric mixture of the A1- and A2-pyrrolines can inter-react to yield the 3-(2-pyrrolidinyl)-A -pyrroline and any attempt to isolate the pure A -pyrroline results in the... 

Finally a general approach to synthesize 42-pyrrolines must be mentioned. This is tl add-catalyzed (NH4C1 or catalytic amounts of HBr) and thermally (150°C) induced rea rangement of cyclopropyl imines These educts may be obtained from commerdal cyan acetate, cyclopropyl cyanide, or benzyl cyanide derivatives by the routes outlined below. Tl rearrangement is reminiscent of the rearrangement of 1 -silyloxy-1 -vinylcyclopropanes (p. 7 83) but since it is add-catalyzed it occurs at much lower temperatures. A2-Pyrrolines constitut reactive enamines and may be used in further addition reactions such as the Robinson anei lation with methyl vinyl ketone (R.V. Stevens, 1967, 1968, 1971). 

Generalization of this result to imines of conjugated aldehydes provides a good synthesis of the A2-pyrroline ring. The intermediacy of an ylid is confirmed by trapping with iV-phenylmaleimide, which takes place with excellent stereocontrol.330... 

Imidates, generated from secondary amides, are treated with trimethylsilyhnethyl triflate to give an azomethine ylid which reacts with electron-poor alkenes and acetylenes, yielding A2-pyrroline and pyrrole derivatives.54 Similar transformations are conducted from thioamides (vide infra). 

This above result was only obtained with maleimide as the dipolarophile. With dimethyl fumarate and fumaronitrile, A2-pyrrolines are obtained, probably because of the acidity of the hydrogen atoms a- to ester and nitrile functionalities. Reaction with alkynes produces pyrrole derivatives in good to excellent yields and with aromatic aldehydes leads regioselectively to oxazolidines in moderate yields.263... 

Alkylation of heterocyclic enamines proceeds similarly to the alkylation of Fischer s base discussed above. Lukes and Dedek223 obtained on methylation of l-methyl-2-ethylidenepyrrolidine (51) a C-alkylation product, i.e. 1 -methyl-2-isopropyl-A2-pyrroline (52). Alkylation of the same enamine with ethyl bromoacetate 224 was the first synthetic step in the preparation of DL-pseudoheliotridane. 

The type-2 systems are the basis of a new type of very potent photochromic compounds. Several routes to this type of system have been developed recently. Incorporation of a A2-pyrroline ring into a more complex molecule has led to a very efficient new class of photochromic compounds (Scheme 2). 

Dimethylethylamine (144) Ar,AT-Dimethylpropylamine (146) Ar,AT-Dimethylisobutylamine (148) Ar,Ar-Dimethyl-2-butylamine (150) 1-Propylpyrrolidine (152) 2-Methyl- 1-propylpyrrolidine (154) 2-Methyl-1-propylpiperidine (156) 2-Methyl- 1-propylmorpholine (158) Cyclopentylpyrrolidine (160) l,2-Dimethyl-A2-pyrroline (162) 1,2-Dimethylpiperidine (164) l-Methyl-3,5-diethyl-l,2,3,4-tetrahydropy-ridine... 

Two entirely different methods utilizing A2-pyrrolines as intermediates have been published. Storesund and Kolsaker prepared heavily substituted pyrrolizidines by base-catalyzed dimerization of nitriles.63 Initial reaction of the dinitrile starting material (97) is presumed to generate a cyclopropane... 

Nucleophilic attack at the methoxyl carbon of this compound liberated an open-chain acetal anion, which acted as a powerful nucleophile and attacked a further cyclopropane molecule in a Thorpe reaction [Eq. (28)]. Rearrangement then produced a A2-pyrroline (99) in an overall yield of 60%. On addition of acid, this A2-pyrroline aromatized with a simultaneous 1,2-methyl shift and formed the dihydropyrrolizines (100). A mixture of products is obtained because hydrolysis of the acetal function competes with the final ring closure reaction. 

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