β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• atoms of not only the syn-stereoisomers but also the β-amino compounds derived from α,β-unsaturated ketones. This hypothesis can be supported by an unexpected transformation. When aziridine 7-B was purified by flash column chromatography, part of the aziridine ring was opened by a chlorine anion to form

• the α-amino-β-chloro Weinreb amide derivative 8 (Scheme 5). This could be confirmed by mass spectroscopic analysis as well. In its mass spectrum, a prominent peak denoting [NsNHCHC(O)NMe(OMe)]+ (m/z = 302) was exclusively observed. Because compound 8 was derived from trans-aziridine, it should be the

• to aziridines. Resonance structures of Weinreb amides. Transformation of trans-aziridine. Proposed mechanism of aminochlorination of α,β-unsaturated Weinreb amides. Optimization of aminochlorination of N-methoxy-N-methylcinnamoylamide (5a). Results of aminochlorination of α,β-unsaturated Weinreb

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• Dodd et al. published a synthesis of protected enduracididine using an azide ring opening of a chiral aziridine as the key step (Scheme 3) [55]. The 9-phenylfluorenyl (PhF) protecting group was employed to help prevent undesired copper coordination during the key aziridation step. The synthesis relied

• on the stereoselective formation of aziridine 27. This key reaction proceeded from allylglycine 28 in 28% yield to give a 7:3 mixture in favour of the S,S diastereomer. Attempted optimisation of the yield and diastereoselectivity afforded no improvement. The synthesis continued with aziridine opening

• (1) and (±)-allo-enduracididine (3) reported by Du Bois et al. arose from the methodology for the conversion of alkenes to diamines via a cyclic sulfonamide intermediate using rhodium catalysis (Scheme 9) [63]. The reaction proceeds with formation of an intermediate aziridine 53 which rearranges upon

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• -piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions

• . Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step. Keywords: α-ketoamides; aziridines; multicomponent reactions; nitrogen heterocycles; one-pot reactions; peptide mimics; vicinal tricarbonyl compounds; Introduction Aziridine

• for the preparation of peptides [2][3] and the synthesis of peptide-like compounds comprising the aziridine motif [4][5]. Furthermore, the incorporation of an electrophilic aziridine moiety in peptide or peptidomimetic frameworks is an interesting strategy for the design of active site-directed drugs

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• acyclic α-aminophosphonates 176. However, using difunctionalized electrophiles such as 1,3-diiodopropane 178 resulted in piperidinylphosphonates 179 with moderate yields (Scheme 38). This one-pot transformation involves an aziridine ring opening, C-alkylation, and hydrophosphorylation of the formed imine

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• starting materials. The reaction proceeds with excellent regio- and diastereoselectivity which is presumably due to a regio- and stereoselective alkene insertion into the strained metalla-aziridine intermediate 84. Photoredox catalysis Visible-light photoredox catalysis has emerged as a powerful platform

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• , Lin and Wang et al. [76] reported the cascade reactions between N-tosylaziridines 78 and hydrazones 79 which led to the synthesis of tetrahydrotriazines 80. The cascade aziridine ring opening and copper-catalyzed intramolecular C–H sulfonamidation via intermediate 81 characterizes the whole reaction

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• to form a cyclic imine – a highly strained three-membered 2H-azirine, 4. Subsequent attack by the acid results in the aziridine adduct 5, which then undergoes intramolecular nucleophilic addition on the carboxylic group with the nitrogen lone pair, ultimately yielding α-amido-1,3-diketone 3 by ring

• ethyl acetate (3 × 10 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo to afford oxazole 8a (yield: 1.52 g; 60%). Formation of substituted aziridine. Various strategies for the formation of 2H-azirine. Synthesis of α-amido-1,3-diketone (3a–o). Reaction

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• aziridine 7 – was optimized in a one-pot procedure using t-BuOK in THF. Nucleophilic ring opening of the aziridine 7 by homoveratryl alcohol in the presence of a catalytic amount of the Lewis acid BF3·OEt2 furnished compound 8. The -NHBoc was deprotected using 4 M HCl in 1,4-dioxane. The free amine 9

Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines from aziridines

• Hongnan Sun,
• Binbin Huang,
• Run Lin,
• Chao Yang and
• Wujiong Xia

Beilstein J. Org. Chem. 2015, 11, 524–529, doi:10.3762/bjoc.11.59

• : ammonium persulfate; aziridine; metal free; morpholine; Introduction Morpholines are common structural cores of a broad range of biological and pharmacological natural or synthetically important organic molecules [1]. In particular, a number of 2-substituted and 2,3-disubstituted morpholines are

• substitution [31]. Under identical reaction conditions, the separable 2-butylmorpholine 3n and 3-butylmorpholine 4n could be easily prepared from aziridine 1n (Table 2, entry 14). To further investigate the applicability of this strategy in organic synthesis, we next performed a series of experiments to

• mechanism was proposed as shown in Scheme 4. Initially, aziridine 1a might participate in single-electron transfer (SET) with the persulfate anion to render the radical cation A [32][34]. Concerted ring opening and nucleophilic addition leads to amino radical intermediate B, which is converted to the

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• -azabicyclo[3.2.1]oct-2-ene and/or 5,7-dioxa-1-azabicyclo[4.3.1]deca-3,8-diene-2-one derivatives. According to DFT calculations (B3LYP/6-31+G(d,p)), the cycloaddition can involve two modes of nucleophilic attack of the dihydroazireno[2,1-b]oxazole intermediate on acetyl(methyl)ketene followed by aziridine

• derivatives were reported [27][28][29]. As also known, the azomethine ylide derived from N-benzylideneanisidine and diazoacetylacetone under Rh2(OAc)4-catalysis undergoes 1,3-cyclization to an aziridine derivative in high yield, rather than 1,5-cyclization [22]. However, no cyclizations of azirinium ylides

• followed by cyclization provides two isomeric adducts 6j and 7j. There are two reasonable pathways to these unexpected products. The first pathway involves the addition of bicycle 10j to ketene 12 to form atropoisomeric azirenooxazolium betains 13j,13′j (Scheme 4) which can further undergo aziridine ring

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• an intermediate aziridinium ion (R)-13 upon heating in MeOH, which is then attacked by amine at the more hindered carbon atom of the aziridine ring. These observations allowed us to propose the following plausible mechanism (Scheme 5), postulated mainly on the basis of the signs of specific rotation

• )-13 is opened exclusively at the more hindered aziridine carbon atom since the respective products (S)-(−)-9 or (S)-(−)-10 (23–46% yield) and (S)-16 (<25% yield) have been isolated in majority, while yield of (S)-17 and both unwanted isomers (S)-14 or (S)-15 remained negligible (<5%). The outcome of

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• flask at −78 °C still renders attractive results, addition of dienophile to 58 and vice versa leads to significantly lower yields. Due to the synthetic usefulness of aziridines, the aziridination of olefins is of particular interest for organic chemists [3]. The three-membered aziridine ring exhibits an

• acetic acid (1:1 molar ratio) in acetonitrile serves as electrolyte. The presence of acetate turned out to be crucial for aziridine formation, since with the use of other supporting electrolytes such as Bu4NBF4 the formation of the desired product could not be observed. Apparently, acetate ions are

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• strand will need to be filled in with orthogonal 5' to 3' chemistry. A dT nucleoside analog with an exocyclic aziridine moiety has been chemically incorporated into poly-T ODN. Upon hybridization with a complementary poly-A strand, the aziridine group is attacked by the exocyclic amino group of the

• opposing adenine, resulting in ring opening and formation of an ethylene cross-linked base pair [29][30]. Other aziridine-substituted nucleobases have been incorporated enzymatically by a DNA polymerase, but elongation past the modified nucleoside has not been reported [31]. Another approach uses

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• tryptophans are limited and include both the catalytic and non-catalytic union of 2-alkylindole with a protected aziridine-2-carboxylate or an α-aminoenoate [38][51][52][53][54] or directly from 2-unsubstituted protected tryptophan and the appropriate nucleophiles via a 3-chloroindolenine intermediate [55][56

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• 57 (Scheme 8) [62]. Thus, addition of the anion of phosphonamide 47a to tert-butyl glyoxylate O-protected oximes affords the corresponding aziridine adducts 57 in excellent diastereoselectivity in a Darzens-type reaction via intermediate 56. This aziridination methodology was then used in the

• cyclization to form the aziridine ring after elimination of chloride. When N-substituted aromatic imines are used, the corresponding aziridines can be reduced at the benzylic carbon to give α-aminophosphonic acids [64]. Synthesis of phosphonamides There are four major methods for the synthesis of

• bearing a chiral oxazolidinone auxiliary, facile access to the cis-aziridine series was possible by using chiral chloroallyl phosphonamide 47a. Thus, the addition of the anion of 47a to tert-butylglyoxylate O-benzylamine (139) led to aziridine 140 as a single diastereomer. Ozonolysis followed by reductive

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• product can be easily converted into aziridines [33][34] and α,β-dehydroamino acid derivatives [35] in the presence of an organic amine. Recently, we found that treating haloamine with benzylamine resulted in an unexpected α,β-diamino product, instead of the aziridine or the α,β-dehydroamino product

• methodology, other common primary or secondary amines, were tested in the reaction under optimized conditions (Table 2). The use of aliphatic amines, such as methylamine (Table 2, entry 2), dimethylamine (Table 2, entry 3) and ammonia solution (Table 2, entry 4), lead to the formation of the aziridine as the

• their properties. Finally, some reactions were additionally conducted to gain insight into the reaction mechanism. First, we prepared the aziridine 6 according to the reported method with cinnamic ethyl ester as starting material [33]. Then, we used the aziridine 6 as starting material to react with

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• alcohol, aziridine, aldehyde and epoxide halogenation reactions from which the desired products are easily isolated and the phosphine oxide byproduct is readily recycled. Results and Discussion Rasta resin 16 was prepared by oxidation of 14, which was prepared as previously reported [28], using H2O2

• electron-rich aldehyde starting materials were used (Table 2, entries 9–12). These results are generally similar to what was previously reported by Denton and co-workers when similar substrates were used [12]. Aziridine halogenation reactions using 16 We next examined the use of 16 as a precursor to 17a

• and 17b in aziridine halogenation reactions [34]. Using reaction conditions similar to those used for the Appel and aldehyde halogenation reactions, a variety of N-tosyl aziridines 8 were successfully converted into the corresponding chloro- or bromotosylamides 9 in excellent yields (Table 3). The

Synthesis of chiral N-phosphoryl aziridines through enantioselective aziridination of alkenes with phosphoryl azide via Co(II)-based metalloradical catalysis

• Jingran Tao,
• Li-Mei Jin and
• X. Peter Zhang

Beilstein J. Org. Chem. 2014, 10, 1282–1289, doi:10.3762/bjoc.10.129

• 85% ee). In addition to mild reaction conditions and generation of N2 as the only byproduct, this new metalloradical catalytic system is highlighted with a practical protocol that operates under neutral and non-oxidative conditions. Keywords: asymmetric aziridination; aziridine; chiral porphyrin

• , suffered from low-yielding formation of the desired aziridine products. To improve the efficiency and control the enantioselectivity of the nitrene transfer process, we then developed a new Co(II)-based metalloradical catalytic system by employing D2-symmetric chiral amidoporphyrins as the supporting

• ligands [28]. It was shown that the chiral metalloradical catalyst [Co(P1)] (P1 = 3,5-DitBu-ChenPhyrin) could catalyze the formation of optically enriched phosphoryl aziridine through direct aziridination of alkenes with DPPA (Scheme 2) [21]. While this [Co(P1)]/DPPA catalytic system represented the first

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• zwitterionic intermediates 9a,c which further cyclize to bisadducts 3a,c. The barriers for addition of the azirine and aziridine nitrogen lone pair of 1a,c, and 8a,c to ketene 6a increase in passing from compounds 1a, 8a to compounds 1c, 8c, because of a decrease in the nucleophilicity of the latter due to the

• electron withdrawing effect of the nitro group. As for possible routes for the formation of adducts 4 and 5, the first (Scheme 2, (a)) involves cleavage of the aziridine ring of intermediate 8 to generate azomethine ylide 10, and further “dimerization” of the latter. Examples of compounds that can be

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• and thermally cyclized to a bicyclic aziridine. The opening of the aziridine with organocuprate led to a corresponding chiral hydroxylated amino acid core [20]. Although a number of chiron approaches are known [21], there is no report from D-glucose towards the synthesis of (2S,3R)-AHDA (2a) and its

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• secondary OH group proceeded (with PPh3 and P(OEt)3) in very high chemoselectivity most likely due to steric effects. The corresponding aziridine of 9a clearly resulting from activation of the secondary hydroxy group and subsequent fast 3-exo-trig cyclisation was only obtained as a sideproduct at higher

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• –cyclopentene rearrangement [13][14] has been shown to be the major competing side reaction in this case. Nitrogen variants Three different approaches can be used to incorporate nitrogen into the DVCPR. The cis-divinylaziridine rearrangement (311 to 312, see Scheme 38) after rhodium-catalyzed aziridine

• formation between vinyl-diazo compound 317 and imine 318 has been found by Doyle [224][225][226]. Rearrangement occurred smoothly to give desired dihydroazepine 320. Note that the authors suggest a transition state including an opened aziridine zwitterion. Alternatively, a cyclopropylamine can be used in an

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• aziridines. Aziridines (1, Figure 1) are generally very stable, in marked contrast with their oxygenated counterparts, the epoxides. However, if one or two fluorine atoms are attached to the aziridine backbone, the resulting molecule is much more susceptible to hydrolysis. De Kimpe and co-workers have

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. Keywords: aziridine; desymmetrization; enantioselectivity; epoxide; organocatalysis

• , when p-nitrophenylsulfonylaziridine (Ns-aziridine) was employed as substrate, the corresponding N-Ns thioamine 8 was obtained in quantitative yield but with moderate enantioselectivity (55% ee). The need of two equivalents (equiv) of CsOH·H2O as a base in the procedure limited its application in

• (3% ee). The usage of Boc for the N-protected group in aziridine resulted in no enantioselectivity under the optimum conditions. The organocatalytic enantioselective ring-opening of N-protected aziridines by β-ketoesters by means of cinchona alkaloid-derived PTCs (Figure 3, OC-12 to OC-19) for