Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• first-generation strategy employed a stereoselective thermal aziridination of azidoformate 2 and a subsequent aziridine-opening reaction to establish the vicinal trans nitrogen motif 4 [26]. The second-generation strategy involved the radical aminobromination of azidoformate 3 followed by lactamization

Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

• Ashley N. Jarvis,
• Andrew B. McLaren,
• Helen M. I. Osborn and
• Joseph Sweeney

Beilstein J. Org. Chem. 2013, 9, 852–859, doi:10.3762/bjoc.9.98

• -sulfonylation in aziridine chemistry, due to the ability of the group to activate the ring and the relative ease of its removal at the conclusion of a synthetic manipulation. We report here in full [30] the results of our studies on the synthesis of N-Dpp vinyl azidirines, and selected ring-opening reactions of

• a reaction of this anion with N-Dpp benzaldimine at −78 °C in the presence of solid ZnCl2, which delivered predominantly (E)-aziridine 1 (3J = 2.6 Hz; d.r. = 10:1) [39] in 58% yield (after purification by column chromatography) at the first attempt (Scheme 1). To our knowledge, this was the first

• reported direct synthesis of a vinyl aziridine bearing a phosphorus group on nitrogen [40]. Encouraged by this promising result, we next examined the scope of the reaction by using the same anion and N-Dpp imines derived from 4-bromo- and 4-fluorobenzaldehyde, furfural and 2,2-dimethylpropionaldehyde

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• ; Introduction Amino acids are the fundamental building blocks of life on earth, and consequently their molecular structure is ubiquitous in natural and synthetic chemistry [1]. An attractive method of installing the amino-acid functionality is through the regioselective ring opening of an aziridine-2

• -carboxylate (Scheme 1) [2][3]. Such a methodology has been developed for N-functionalised aziridines [4][5][6][7][8][9], as N-functionality offers both activation of the aziridine to ring opening [10], and protection of the nitrogen. However, an extra synthetic step may be required to remove the N

• -opening protocols have been developed, synthesis of the starting NH-aziridine-2-carboxylates is multistep and low-yielding. Synthetic routes include Gabriel–Cromwell addition of ammonia to an enoate [16][17]; epoxide opening with azide, followed by ring closure [19]; and a sequence of olefin

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• kJ/mol. In the case of saturated, acyclic substituents the trend ‘longer alkyl chains – higher MCA values’ is again observed (Figure 6). For saturated, cyclic substituents, however, the MCA values increase from aziridine (134) to azetidine (140) and pyrrolidine (148), but then decrease again for

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• -lactam to γ-lactam ring expansions [29][30], aziridine ring openings followed by cyclization with enolates [31], palladium-catalyzed cyclizations [32], cycloadditions [33], multicomponent reactions [34], and even NHC catalysis [35][36]. Nevertheless, the methodology developed by Rovis indisputably

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• ). Furthermore, in order to provide access to the class of 2-aminopropan-1,3-diols, aziridines 7 were evaluated for the first time as substrates for a water-induced aziridine ring opening in an acidic medium. Thus, treatment of trans-2-aryl-3-(hydroxymethyl)aziridines 7 with one equiv of para-toluenesulfonic

• opening of the aziridine moiety at C2 due to benzylic stabilization of the developing carbenium ion in an SN2 fashion [30]. As the use of imines bearing a N-tert-butyl group in combination with a substituent in the ortho-position of the aromatic ring is known to afford the corresponding cis-4-aryl-3

• , the aziridines 11, which have previously been shown to be unreactive towards LiAlH4 and methanol and thus unable to undergo ring opening [30], were used as substrates for a water-induced ring opening through initial protonation of the aziridine ring with p-TsOH. Although more drastic reaction

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• aminated amine-linked sec–sec structures by aziridine-opening reactions (ionic liquid, 120 °C) [9]. Primary–sec amine-linked structures have been synthesised by Thiem et al., through a reductive amination strategy [10][11]. In contrast, related structures containing an amine linkage between a carbohydrate

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

• Paul W. Davies,
• Nicolas Martin and
• Neil Spencer

Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96

• other reports into π-acid promoted alkynyl aziridine cycloisomerisations without skeletal rearrangement [20][21][22][23]. Our working mechanism to explain this reaction divergence centred on the electrophilic activation of the alkyne in A triggering a ring-expansion to a common intermediate B from which

• 1,2-aryl shift in preference to either proton elimination or a 1,2-hydride shift. We therefore sought to validate this proposal experimentally by isotopic labelling. Results and Discussion A deuterium labelled precursor Alkynyl aziridine 4 was selected as the initial probe for the mechanism which

• requires fission of three bonds: The propargylic C–N bond in ring expansion; the aryl–aziridinyl C–C bond in the 1,2 shift and the propargylic C–H bond for aromatisation (Scheme 3). The positioning of a deuterium atom at the benzylic carbon in 4 enables the carbons of the aziridine ring to be distinguished

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• substituted novel pyrroline derivatives have been synthesized by this methodology and the products can be used as key intermediates in the synthesis of substituted pyrrolines, pyrroles and pyrrolidines. Keywords: 5-alkyl/aryl/heteroaryl substituted 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates; aziridine; N

• -vinyl substituted aziridines; ring expansion; sodium iodide; Introduction Vinylaziridines are a particularly interesting class of aziridine derivatives that lend themselves to a host of highly useful synthetic transformations [1]. They are versatile electrophiles and notably undergo regioselective ring

• opening via addition at either the vinyl terminus [2][3][4][5] or directly at the aziridine ring carbon depending on the reagents employed [6][7]. Vinylaziridines have also been exploited in a variety of ring expansion reactions to afford a range of heterocyclic products, including piperidines [8][9

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• nitrogen atoms. However, flash vacuum pyrolysis at 500 °C leads to loss of molecular nitrogen (N2) to produce aziridine. Certain triazoles are relatively easy to cleave by ring–chain tautomerism. Synthesis of triazoles Substituted 1,2,3-triazoles can be produced by the azide–alkyne Huisgen cycloaddition in

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• , in one isolated example, the N-Boc-aziridine of styrene was treated with s-BuLi in THF at –98 °C to give a phenyl-stabilised α-lithiated aziridine, which underwent migration to give 2-phenyl-2-Boc-aziridine (90%) [23]. Also, our laboratory has reported the LTMP (lithium 2,2,6,6-tetramethylpiperidide

• )-induced rearrangement of a range of terminal N-Boc-aziridines to give trans-aziridinyl esters [12][15] (cf. Scheme 1, with CO2t-Bu instead of PO(OEt)2). However, prior to our studies only one example of a N- to C-[1,2]-anionic rearrangement of an aziridine involving phosphorus had been observed

• : lithiation-deuteration of N-diphenylphosphinylaziridine 10 gave the anticipated deuterated aziridine 11 (70%), along with the rearranged aziridine 12 (25%) [24] (Scheme 3). Results and Discussion So as to examine the migration chemistry outlined in Scheme 1, access to N-phosphonate terminal aziridines 1 was

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• structural elucidation was remarkable at that time considering the presence of 4 contiguous stereogenic carbons in the molecule. The tetracyclic pyrrolo-indole skeleton of a mitomycin is embellished with an aziridine ring, a carbamoyl moiety and a bridged carbinolamine packed in a constrained architecture [2

• unique activity was thought to originate from their ability to transform in vivo to generate the active metabolite. This was followed by decades of investigations to understand in detail their singular mode of action. It was found that the aziridine played a crucial role, allowing an irreversible bis

• -alkylation of DNA [3]. The decisive role of the aziridine is far from unusual since its presence in a small number of other naturally occurring molecules such as azinomycins [4][5], FR-900482 [6], maduropeptin [7], and azicemicins [8] is accompanied by significant biological properties (Scheme 1) [3][9

The enantiospecific synthesis of (+)-monomorine I using a 5-endo- trig cyclisation strategy

• Malcolm B. Berry,
• Donald Craig,
• Philip S. Jones and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2007, 3, No. 39, doi:10.1186/1860-5397-3-39

• -mediated 5-endo-trig methodology. [3] we embarked on the total synthesis of the indolizidine alkaloid monomorine I, the trail pheromone of the Pharaoh worker ant Monomorium pharaonis. [10] Our initial synthetic plan is outlined in Scheme 2; aziridine 6, prepared from D-norleucine by standard

• )aziridine 9 by ring-opening with 1 followed by protecting group interchange. Although this strategy was not as elegant as utilising an N-benzoylaziridine directly, we deemed it prudent not to subject such a species to nucleophilic attack due to reported issues with chemoselectivity. [17] Careful

• transformation as the key step in the synthesis of the indolizidine alkaloid, (+)-monomorine I. The synthesis was achieved in nine steps from the readily available aziridine 18, and compares favourably with other total syntheses in the literature. See Supporting Information File 1 for full experimental data

Pd-catalysed [3 + 3] annelations in the stereoselective synthesis of indolizidines

• Olivier Y. Provoost,
• Andrew J. Hazelwood and
• Joseph P. A. Harrity

Beilstein J. Org. Chem. 2007, 3, No. 8, doi:10.1186/1860-5397-3-8

• [3 + 3] annelation of enantiomerically pure aziridine 7 provides the functionalised piperidine 8 that can be elaborated to the indolizidine skeleton in only 4 steps with good stereocontrol. Introduction Indolizidine alkaloids represent one of the most structurally diverse classes of natural products

• intermediate 4 within a few steps. We wish to report herein our recent progress towards this goal. Our studies began with the preparation of an appropriate precursor to the desired functionalised piperidine (Scheme 2). Specifically, we prepared an enantiomerically pure silyl protected aziridine 7 using a

• smoothly transformed to aziridine 7 after Mitsunobu condensation. Having arrived at the key [3+3] annelation step, we decided to employ our standard conditions for the Pd-catalysed reaction. Indeed, we were pleased to find that the desired piperidine 8 could be furnished in high yield and that this