Reaction of azomethine ylides with sulfur ylides. Novel azetidine synthesis

Vaultier, Michel; Danion-Bougot, R.; Danion, D.; Hamelin, J.; Carrié, R.

doi:10.1021/jo00908a043

Cited by 32 publications

(23 citation statements)

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“…Dimethyloxosulfonium methylide was demonstrated to be a suitable reagent for the nucleophilic ring expansion of three-membered heterocycles. It was successfully applied in the preparation of oxetanes and azetidines via the ring expansions of oxiranes [116][117][118] and aziridines [119,120]. However, both thiiranes and thietanes were less stable than the corresponding oxa and aza-analogs.…”

Section: Synthesis Via Nucleophilic Ring Expansion Of Thiiranesmentioning

confidence: 99%

Recent synthesis of thietanes

Xu¹

2020

Beilstein J. Org. Chem.

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Thietanes are important aliphatic four-membered thiaheterocycles that are found in the pharmaceutical core and structural motifs of some biological compounds. They are also useful intermediates in organic synthesis. Various synthetic methods of thietanes have been developed, including inter- and intramolecular nucleophilic thioetherifications, photochemical [2 + 2] cycloadditions, ring expansions and contractions, nucleophilic cyclizations, and some miscellaneous methods. The recently developed methods provide some new strategies for the efficient preparation of thietanes and their derivatives. This review focuses on the synthetic methods to construct thietane backbones developed during 1966 to 2019.

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Section: Synthesis Via Nucleophilic Ring Expansion Of Thiiranesmentioning

confidence: 99%

Recent synthesis of thietanes

Xu¹

2020

Beilstein J. Org. Chem.

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“…1 H NMR (CDCl 3 ): δ 1.08 and 1.10 (2 × 3H, d, J = 6.5 Hz, (CH 3 ) 2 -CH), 1.49 (3H, s, CCl-CH 3 ), 2.35 (3H, s, CH 3 -C 6 H 4 ), 2.86 (3H, s, CH 3 SO 2 ), 3.29 (1H, septet, J = 6.5 Hz, (CH 3 ) 2 -CH), 6.59 (1H, s, CH-OMs), 7.11−7.22 (4H, m, 4 × CH ar ), 7.36 (2H, d, J = 8.7 Hz, 2 × CH ar ), 7.56 (2H, d, J = 8.7 Hz, 2 × CH ar ). 13 C NMR (CDCl 3 ): δ 21. 5, 23.4, 23.6, 26.7, 39.7, 54.0, 74.8, 86.1, 127.0 (2 × CH ar ), 128.5 (2 × CH ar ), 129.1 (2 × CH ar ), 131.1 (2 × CH ar ), 132.6, 133.8, 135.5, 138.4, 167.9 3,23.2,23.4,26.8,39.5,53.7,74.8,87.1,128.0 (3 × CH ar ClNO 3 S: C 61.83,H 6.42,N 3.43.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…8, 22.9, 23.0, 37.9, 53.9, 83.9, 127.3 7.22 (2H, d, J = 7.7 Hz, 2 × CH ar ). 13 C NMR (CDCl 3 ): δ 21. 3, 22.7, 22.9, 23.0, 37.9, 53.8, 84.1, 127 .…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…To the best of our knowledge, the only report on the synthesis of such type of 3-haloazetidines with carbon-centered substituents at the 1-, 2-, 3-, and 4-positions involves the reaction of 1,2,2,3-tetrasubstituted aziridines or substituted 4-oxazolines, via the corresponding intermediate azomethine ylides, with sulfur ylides. 13 The aldol step has been investigated by means of theoretical calculations in order to better understand the effect of metal-coordination in the transition state structures and its effect on the diastereoselective outcome.…”

Section: ■ Introductionmentioning

confidence: 99%

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Diastereoselective Aldol Reaction of Zincated 3-Chloro-3-methyl-1-azaallylic Anions as Key Step in the Synthesis of 1,2,3,4-Tetrasubstituted 3-Chloroazetidines

et al. 2012

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Zincated 3-chloro-3-methyl-1-azaallylic anions undergo a stereoselective aldol addition across aromatic aldehydes and subsequent mesylation to produce syn α-chloro-β-mesyloxyketimines, which were isolated in 80−84% yield and high diastereomeric excess (dr > 97/3) after purification via flash chromatography. The syn α-chloro-β-mesyloxyketimines were further stereoselectively reduced to give stereochemically defined 3-aminopropyl mesylates, which were cyclized to 1,2,3,4-tetrasubstituted 3-chloroazetidines containing three contiguous stereogenic centers. DFT calculations on the key aldol addition revealed the presence of a highly ordered bimetallic six-membered twist-boat-like transition state structure with a tetra-coordinated metal cyclic structure. DFT calculations revealed that chelation of both zinc and lithium cations in the transition state structure leads to the experimentally observed high syn diastereoselectivity of aldol reactions. ■ INTRODUCTIONThe stereoselective synthesis of azetidines, particularly of highly substituted derivatives, represents an underdeveloped research area, despite their importance as a class of strained azaheterocyclic compounds, which occur in a wide range of natural products and with application in medicinal chemistry for the synthesis of bioactive compound libraries.1 3-Haloazetidines, in particular, form an important subclass of functionalized four-membered azaheterocycles due to their potential physiological activities and their use as synthons in the synthesis of 3-substituted azetidine derivatives.2 Only very recently, our group reported the first asymmetric synthesis of trans-2-aryl-3-chloroazetidines via cyclization of optically pure β-chloro-γ-sulfonylamino alcohols under Mitsunobu conditions. 3 The latter result, together with a variety of other examples, 1h,4 demonstrated that the cyclization of a preformed aminopropyl chain via nucleophilic substitution of a leaving group, such as a chloride, bromide, or an activated hydroxyl group, in the γ-position, forms a general method to prepare azetidines. The applicability of this method for the stereoselective synthesis of highly substituted 3-haloazetidines 3 depends, naturally, on the efficient synthetic accessibility of the corresponding stereochemically defined aminopropyl precursors 2 (Scheme 1). Metalated 3-chloro-1-azaallylic anions 1 5 have proven to be suitable building blocks in organic synthesis by reaction with electrophiles and elaboration of the resulting functionalized α-chloroketimines.6 More specifically, the aldol reaction of 3,3-dichloro-1-azaallylic anions 1 (R 3 = Cl) with aromatic aldehydes, followed by mesylation to the corresponding β-mesyloxyketimines, 7 and reduction afforded amines 2 (R 3 = Cl) as precursors of stereochemically defined 2,4-diaryl-3,3-dichloroazetidines 3 (R 3 = Cl). 8 In previous computational research, the 3-chloro-3-methyl-1-azaallylic anion 1 (R 3 = Me) was chosen as a model compound to obtain deeper insight into the structural features of 3-halo-1-azaallylic anions a...

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“…In separate experiments, cyclopropane 3a was found to be unreactive to the ylide 5 even when treated in large excess. Although, cyclopropanes are known not to react with excess DIM-SOY to give cyclobutanes, DIMSOY can add to epoxides and suitably N-protected aziridines under harsh conditions to give oxetanes [64][65][66][67][68] and azetidines [69,70] or other products [71][72][73][74][75][76], depending on the other functionalities present on the substrates. A plausible mechanism for the formation of cyclobutane products from silyl substituted methylene malonates 2 is delineated in Scheme 7.…”

Section: Preparation Of Cyclobutane Derivativementioning

confidence: 99%