Synthesis of functionalized cyclopropanes by MIRC reactions of aziridinyl-methylenemalonates

Funaki, I.; Bell, R.P.L.; Thijs, L.; Zwanenburg, B.

doi:10.1016/0040-4020(96)00712-0

Cited by 21 publications

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“…The best results were obtained with alkylmagnesium halides in the presence of 10 mol% of copper(I) cyanide (Scheme 10) [15]. A similar MIRC reaction was performed with oxiranyl derivatives [17].…”

Section: Methodsmentioning

confidence: 92%

Section: (Scheme 2)mentioning

confidence: 99%

“…Another fruitful application of the heterocyclic esters 1 and 2 involves the Knoevenagel reaction of the aldehyde 19 obtained by reduction of the ester function (Scheme 10) [15].…”

Section: (Scheme 2)mentioning

confidence: 99%

“…This reaction could only be accomplished for aziridinecarboxamides in which the amide N-H is replaced by an anisyl or benzyl group. In the latter case, the yield of ␤-lactam was high, however, in the former case a considerable amount of five-membered product 16c was also produced [13,14].Another fruitful application of the heterocyclic esters 1 and 2 involves the Knoevenagel reaction of the aldehyde 19 obtained by reduction of the ester function (Scheme 10) [15].The compounds 20 obtained in this manner undergo a Michael Initiated Ring Closure (MIRC) reaction upon treatment with suitable nucleophiles to give functionalized cyclopropanes 21. The best results were obtained with alkylmagnesium halides in the presence of 10 mol% of copper(I) cyanide (Scheme 10) [15].…”

mentioning

confidence: 99%

“…It was shown that the corresponding cis-aziridinyl-methylene malonates produce predominantly the trans cyclopropane product. The stereochemical course of this MIRC reaction was explained [15] by invoking Yamamoto's model for conjugate additions of cyanocuprates to ␥-alkoxy-␣,␤-unsaturated esters [16].A convenient synthesis of methyl and unsubstituted aziridine-2-carboxylic esters makes use of the readily available amino acids serine (22a) and threonine (22b), respectively, as the starting material (Scheme 11) [18].The tritylated amino acids 23 are treated with two equivalents of methanesulfonyl chloride in the presence of triethylamine to produce 24 in good yields. This method of preparation has attracted High enantioselectivities were obtained for the reduction of acetophenone, comparable with those obtained with Corey's ␣,␣-diphenyl-2-pyrrolidinemethanol as the precatalyst [21].…”

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Synthetic potential of heteroatomic ring systems

Zwanenburg¹

1999

Pure and Applied Chemistry

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The synthesis of aziridine-2-carboxylic acid derivatives of high enantiopurity is described and their synthetic utility is discussed. Ring-opening and ring-expansion reactions of both oxirane and aziridine carboxylic esters are highlighted. Convenient syntheses of ␣-hydroxy, ␤-amino and ␣-amino, ␤-hydroxy carboxylic acids with defined stereochemistry are presented. The preparation of pyrrolidinone and azetidinone derivatives from functionalized three-membered heterocycles is described. Small-ring heterocycles also serve as the basis for the synthesis of catalysts, e.g. for an asymmetric reduction and for cyclopropanation reactions.Functionalized small-ring heterocycles are highly attractive compounds from the synthetic point of view [1]. Aziridine-2-carboxylic esters, for instance, are of interest as they are structurally related to ␣-as well as ␤-amino acids [2], and ring-opening reactions of oxiranecarboxylic acid derivatives allow the preparation of sterically defined ␣,␤-functionalized carboxylic acids. The strain present in these threemembered ring compounds ensures high reactivity in ring-opening and ring-expansion reactions [2]. We have developed a general and convenient synthesis of aziridine-2-carboxylic esters 1 from the corresponding oxiranecarboxylates 2 by successive treatment with sodium azide and triphenylphosphine [3]. The required starting materials in turn were prepared by Sharpless epoxidation of appropriate allylic alcohols [4], followed by oxidation of the 2,3-epoxy alcohols to the corresponding carboxylic acids using either ruthenium tetroxide or a two-step process involving a Swern oxidation and subsequent oxidation with sodium chlorite [3]. The sequence for the conversion of epoxy esters 2 into the aziridine esters 1 is depicted in Scheme 1.The treatment with sodium azide results in an S N 2-ring opening to give, in most cases, a mixture of regioisomeric azido alcohols 3. Without separation this mixture is treated with triphenylphosphine to give the aziridine esters 1 via the intermediacy of oxazaphospholidines 4 [5]. This formation of the threemembered ring by the Staudinger reaction proceeds with inversion at the oxygen-bearing carbon atom. Thus, in the overall process from 2 to 1 an inversion at the ␣ as well as the ␤ carbon atom takes place, with an excellent retention of chiral integrity. The procedure outlined in Scheme 1 has been utilized successfully for the synthesis of (þ)-(2S, 3S)-aziridine-2,3-dicarboxylic acid, a natural product isolated *Lecture presented at the 5th International Conference on Heteroatom Chemistry (ICHAC-5), London, Ontario, Canada, 5-10 July 1998, pp. 369-512.Correspondence: E-mail: zwanenb@sci.kun.nl Scheme 1from Streptomyces MD 398-A1 [6]. It is relevant to note that aziridinecarboxylic acids show the expected behavior for ␣-amino acids in reaction with triethylboron, viz. the formation of boroxazolidines 5 [7]. Regiocontrolled ring-opening reactions of aziridine esters were accomplished with, for instance, thiophenol and indole as the nucleophi...

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Section: Methodsmentioning

confidence: 92%

Section: (Scheme 2)mentioning

confidence: 99%

“…Another fruitful application of the heterocyclic esters 1 and 2 involves the Knoevenagel reaction of the aldehyde 19 obtained by reduction of the ester function (Scheme 10) [15].…”

Section: (Scheme 2)mentioning

confidence: 99%

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confidence: 99%

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Synthetic potential of heteroatomic ring systems

Zwanenburg¹

1999

Pure and Applied Chemistry

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ChemInform Abstract: Synthesis of Functionalized Cyclopropanes by MIRC Reactions of Aziridinyl‐methylenemalonates.

et al. 1997

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Synthesis of Functionalized Cyclopropanes by MIRC Reactions ofAziridinyl-methylenemalonates.-A variety of substituents can be introduced into the resulting cyclopropane derivatives using this route. Starting from trans-substituted aziridines cis-substituted cyclopropanes are formed predominantly, whereas starting from the cis-substituted aziridine ( XIV) the trans-substituted cyclopropane (XV) is obtained. Grignard reactions catalyzed by CuCN give the most promising results. The diastereoselectivity is found to depend on the aziridine substituents as well as on the bulkiness of the reagent. -(FUNAKI, I.; BELL, R. P. L.; THIJS, L.; ZWANENBURG, B.; Tetrahedron 52 (1996) 37, 12253-12274; Dep. Org. Chem., Univ. Nijmegen, NL-6525 ED Nijmegen, Neth.; EN)

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Highly Diastereo‐ and Enantioselective Aziridination of α,β‐Unsaturated Amides with Diaziridine and Mechanistic Consideration on Its Stereochemistry

Ishihara¹,

Hori²,

Sugihara³

et al. 2002

Helvetica Chimica Acta

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Dedicated to Prof. Dieter Seebach on the occasion of his 65th birthday During studies of aziridination of a,b-unsaturated amides with diaziridine, we found that we could prepare both the cis-and trans-aziridinecarboxamides by choosing an appropriately substituted diaziridine. While 3-monosubstituted diaziridine 2 was suitable for the trans-selective aziridination, employment of 3,3-dialkyldiaziridine 1 resulted in the formation of cis-aziridine carboxamides, irrespective of the geometry of the substrate (Scheme 1 and Tables 1 and 2). To elucidate the unique nonstereospecificity and to expand these aziridinations to asymmetric ones, several optically active diaziridines were newly prepared. Aziridination with an optically active 3-monosubstituted diaziridine, 3-cyclohexyl-1-[(1R)-1-phenylethyl]diaziridine 16, proceeded smoothly with high trans-selectivity as well as excellent enantioselectivity (up to 98% ee; see Table 3). On the other hand, highly enantioselective cis-aziridination was achieved (> 99% ee) with optically active 3,3-dimethyl-1-[(1R)-1-phenylethyl]diaziridine 15, though the yield was low (4%). This aziridination was considered to proceed stepwise by way of the enolate intermediate (Scheme 2). Careful inspection of the stereochemistry and its solvent-dependence suggested that the diastereoselection of the reaction was kinetically controlled: the 1,4-addition of N-lithiated diaziridine was a crucial step for determination of the stereochemical course of the aziridination (Figs. 2 ± 4).

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Synthesis of functionalized cyclopropanes by MIRC reactions of aziridinyl-methylenemalonates

Cited by 21 publications

References 42 publications

Synthetic potential of heteroatomic ring systems

Synthetic potential of heteroatomic ring systems

ChemInform Abstract: Synthesis of Functionalized Cyclopropanes by MIRC Reactions of Aziridinyl‐methylenemalonates.

Highly Diastereo‐ and Enantioselective Aziridination of α,β‐Unsaturated Amides with Diaziridine and Mechanistic Consideration on Its Stereochemistry

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