Addition of lithiated methoxyallene 2 to imines provided the expected allenyl amines in good yield. These could be cyclized with base or with silver nitrate to a variety of 2,5-dihydropyrrole derivatives. Selected examples describe their conversion to pyrrolidin-3-ones or 3-methoxypyrroles. Most importantly, this [3+2] cyclization method could also be applied to the synthesis of 2,5-disubstituted derivatives such as 26-28 and also to the preparation of the enantiopure compound 23.Syntheses of pyrrole derivatives are of great importance due to their presence in numerous biologically active compounds. 2 Therefore, many routes leading to this class of heterocycles have been developed. 3 In addition, certain electron-rich pyrrole derivatives are of interest because of their redox behaviour and their ability to provide polypyrroles. 4 Lithiated methoxyallene 2 is an extremely valuable building block for the synthesis of oxygen and nitrogen heterocycles. 5 With carbonyl compounds it provides furan derivatives after cyclization, 6 whereas its reaction with nitrones leads to 1,2-oxazines. 7 Surprisingly, no additions to simple imines have been reported, 8 which should furnish pyrrole derivatives. A recent publication describing reactions of 2 with SAMP-hydrazones providing enantiopure 3-methoxy-2,5-dihydropyrrole derivatives 9 prompts us to report our results with various imines. 10 Lithiated methoxyallene 2 was generated by the standard procedure employing n-butyllithium at -40°C, and after addition of N-tosylimine 1 11 followed by aqueous workup and purification the primary adduct 3 was obtained in 67% yield (Scheme 1). This intermediate could be hydrolyzed with acid to afford an a,ß-unsaturated ketone 10 or, more interestingly, converted into a-amino ester 4 by ozonolysis. 12In analogy to the behaviour of the carbonyl adducts 6 cyclization of 3 employing 0.15 equivalents of potassium tert-butoxide in DMSO furnished the desired pyrrole derivative 6 in 84% yield. Since an excess of base converts 6 into 5, the isomerization 3AE6 is better performed by using of 0.27 equivalents of silver nitrate in acetone 13 which gave a yield of 93%. 14 Cyclization of 3 and elimination of toluene sulfinate from intermediate 6 proceeded by use of 1.5 equivalents of KOtBu and furnished 3-methoxy-2-phenylpyrrole (5) in 71% yield. This compound was also formed by heating the primarily obtained lithium salt of 3 in DMSO. An obvious subsequent transformation of 2,5-dihydropyrrole derivative 6 is the hydrolysis of its enol ether moiety; treatment of 6 with 2N aqueous sulfuric acid provided pyrrolidinone 7 in 96% yield. Analogous experiments were successfully performed with N-tosyl imines derived from pivalaldehyde and cinnamyl aldehyde. Having established that highly reactive imines such as 1 behave similarly to carbonyl compounds, we studied less reactive N-aryl and N-alkyl imines. Scheme 2 presents selected examples of the additions of 2 to readily available imines 8, 10, 12, 15, and 17. Cyclization either with silver nitrate or under basic ...
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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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