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

• - and deuterium-labelled substrates. Keywords: 1,2-aryl shift; cycloisomerisation; gold; isotopic labelling; pyrrole; skeletal rearrangement; Introduction Gold-catalysed cycloisomerisation reactions have emerged as powerful methods to construct a diverse array of hetero- and carbocyclic motifs under

• 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

Single enantiomer synthesis of α-(trifluoromethyl)-β-lactam

• Václav Jurčík,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2011, 7, 759–766, doi:10.3762/bjoc.7.86

• -methylbenzyl-β-lactam 5a with a modest diastereoisomeric bias (~50% de) indicating some epimerisation of the α-trifluoromethyl stereogenic centre, to a thermodynamic product ratio. This was supported in an analytical reaction by the observation of deuterium exchange at this stereogenic centre after the

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• species 12, generated by electrophilic ring-opening of cyclopropene 8, followed by protodeauration of the resulting vinyl gold species 13. Using CD3OD as a nucleophile effectively led to 90% deuterium incorporation at C1 and formation of a mixture of geometric isomers (Scheme 7) [18][19]. Interestingly

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• reveal, 5-exo oxyauration via 16 is restricted by the steric hindrance between the (methoxymethyl)oxy group and the substituents at the quaternary stereocenter. With the aim of trapping the organo–gold intermediate to confirm the mechanism of this reaction, deuterium labeling studies with deuterium oxide

• were performed. Under the same conditions but with the addition of two equivalents of D2O, heterocyclization reaction of MOM protected γ-allenol 14a catalyzed by AuCl3 in dichloromethane afforded [4D]-15a in 48% yield, indicating that a deuterium atom was incorporated at the alkenyl carbon (Scheme 9

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• supported by a deuterium isotopic experiment (Scheme 15). Two molecules of methanol were involved in the transformation and a dimethoxyketal intermediate was formed: The final product was derived from the hydrolysis of this ketal intermediate. When d4-methanol was used as the solvent, a highly deuterated

• found in the products, which clearly supported the intramolecular nature of the oxygen transfer. Liu and co-workers independently reported a very similar gold-catalyzed cyclization of 2-alkynyl aryl epoxide 21 to acylindene 22 (Scheme 18) [53]. A deuterium isotopic experiment was conducted to support

• cyclization of internal diynes. Proposed solvolysis/cyclization mechanism. Gold-catalyzed cyclization of alkynyl epoxides and the 18O isotopic labeling experiment. Proposed oxygen transfer mechanism. Gold or silver-catalyzed cyclization of alkynyl epoxides and the corresponding deuterium labeling experiment.

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• (−)-sparteine and quenched with trimethylsilyl chloride (Scheme 27). Deuterated thiocarbamate 78 containing >99% deuterium was isolated from the reaction with an enantiomeric ratio of 67:33. The high deuterium content of the product indicated that both enantiomers of 77 must have been deprotonated, and thus

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• bridging carbon atom is slightly positively charged, the termini of the allylic moiety carry a partial negative charge. It was shown that the formation of the sigma bonds is the rate determining step, as isotope effects were only observed when the addition occurred directly at the deuterium-substituted

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• from the structure. Deprotonation can be a means for reducing the overall charge on the superelectrophile. Consequently, the deprotonation–reprotonation may be one of the most common means by which charge migrates in superelectrophiles. Several studies have examined this question using deuterium

• , followed by successive hydride shifts to give the charge separated dication 139. Cyclization then leads to the lactone derivative 140. In order to further probe this conversion, the deuterium labeled compound 141 was prepared and reacted under similar conditions. Interestingly, a lactone derivative was not

• formed and only the dicationic species 142 was observed by low temperature NMR. It was proposed that the deuterium atoms slow the initial 1,2-hydride (deuteride) shift and charge migration is inhibited. In another study, the heterocyclic alcohol 143 ionizes in superacid to give the 1,4-dication 144

Chiral recognition of macromolecules with cyclodextrins: pH- and thermosensitive copolymers from N-isopropylacrylamide and N-acryloyl-D/L-phenylalanine and their inclusion complexes with cyclodextrins

• Sabrina Gingter,
• Ella Bezdushna and
• Helmut Ritter

Beilstein J. Org. Chem. 2011, 7, 204–209, doi:10.3762/bjoc.7.27

• chloride (97%) and N-isopropylacrylamide (NIPAAm, 97%) were obtained from Aldrich, Germany, and used as received. Azobisisobutyronitrile (AIBN) (96%) and N,N-dimethylformamide (DMF) were purchased from Fluka, Germany. Dimethylsulfoxide-d6 (99.9 atom % D) and deuterium oxide D2O were obtained from Deutero

• GmbH, Germany. Measurements 1H NMR was performed using a Bruker Avance DRX 500 spectrometer operating at 200.13 MHz or 500 MHz for protons in DMSO-d6 or deuterium oxide (99.9%) as solvents. The δ scale relative to tetramethylsilane was calibrated to the solvent value δ = 4.79 ppm for D2O and 2.51 ppm

Intramolecular hydroxycarbene C–H-insertion: The curious case of (o-methoxyphenyl)hydroxycarbene

• Dennis Gerbig,
• David Ley,
• Hans Peter Reisenauer and
• Peter R. Schreiner

Beilstein J. Org. Chem. 2010, 6, 1061–1069, doi:10.3762/bjoc.6.121

• of matrix-isolated 9 (Scheme 3 and Scheme 4). The [1,2]H-tunneling reactions in hydroxycarbenes can be suppressed by an exchange of hydrogen for deuterium. Hence, carbene signals can readily be identified by prolonged irradiation at or near the maximum absorption wavelength of the carbene. Thus, the

• pyrolysis experiment was repeated with the mono-deuterated acid d-6 (o-MeOC6H4COCOOD) to yield d-8 (OD). Again minor amounts of 9 (without any deuterium incorporation) were formed. In accordance with prior results, neither d-5 nor d-7 could be detected after irradiation. A proposed mechanism for the

• to –OMe), 121.2 (p-C to –OMe), 122.2 (ipso-C to –COCOOH), 126.1 (o-C to –COCOOH), 136.6 (p-C to –COCOOH), 160.0 (ipso-C to –OMe), 166.8 (–COCOOH), 188.1 (–COCOOH). (o-Methoxyphenyl)glyoxylic acid-O-d (d-6) was obtained by repeated dissolution of (o-methoxyphenyl)glyoxylic acid in excess deuterium

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

• product. In the event, quenching a migration reaction of N-phosphonate aziridine 1a with CD3OD did not show any deuterium incorporation. This prompted a closer investigation of the reaction using a more rigorously purified sample of aziridine 1a than which had been used in our preliminary studies. This

Concise methods for the synthesis of chiral polyoxazolines and their application in asymmetric hydrosilylation

• Wei Jie Li,
• Zun Le Xu and
• Sheng Xiang Qiu

Beilstein J. Org. Chem. 2010, 6, No. 29, doi:10.3762/bjoc.6.29

• ), 3.26–3.31 (m, 2H), 3.46 (dd, J = 6.5, 11.0 Hz, 2H), 3.62 (dd, J = 4.0, 11.0 Hz, 2H), 7.23–7.34 (m, 10H) ppm. Among the protons described above, two active hydrogens of OH were substituted by deuterium. ESI-MS, m/z (%): 419 ([M+H]+, 100); Anal. Calcd for C24H22N2O5: C, 68.89; H, 5.30; N, 6.69. Found: C

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• is no clear correlation between the electron deficiency of the arenecarbaldehyde and the reaction yield [4]. Further mechanistic investigations were performed with 1,3-propanediol-1,1,3,3-d4 in order to provide more information about the observed hydride shift. Indeed deuterium was incorporated into

A stable enol from a 6-substituted benzanthrone and its unexpected behaviour under acidic conditions

• Marc Debeaux,
• Kai Brandhorst,
• Peter G. Jones,
• Henning Hopf,
• Jörg Grunenberg,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2009, 5, No. 31, doi:10.3762/bjoc.5.31

• hydroxyl group, with H···O 0.87(2), O···O 2.655(1) Å, O-H···O 174(2)°. The DMSO methyl deuterium D99A forms a short H···π contact of 2.54 Å to the centre of the ring C18-23. The bond length C10-O1 of 1.369(1) Å is consistent with a single bond, and the hydroxy hydrogen was located and freely refined. The

Stereoselective synthesis of (2S,3S,4Z)-4-fluoro- 1,3-dihydroxy- 2-(octadecanoylamino)octadec- 4-ene, [(Z)-4-fluoroceramide], and its phase behavior at the air/water interface

• Gergana S. Nikolova and
• Günter Haufe

Beilstein J. Org. Chem. 2008, 4, No. 12, doi:10.3762/bjoc.4.12

• building block has already been used for the preparation of several γ-fluoro-α-amino acids [31]. This methodology, utilizing the corresponding ethyl iminoglycinate instead of 4, was previously applied for the synthesis of natural D-erythro-sphingosine (1a) [32], deuterium and tritium labeled sphingosines

Part 2. Mechanistic aspects of the reduction of S-alkyl- thionocarbonates in the presence of triethylborane and air

• Florent Allais,
• Jean Boivin and
• Van Tai Nguyen

Beilstein J. Org. Chem. 2007, 3, No. 46, doi:10.1186/1860-5397-3-46

• also be the source of hydrogen. However, the deuterium incorporations in experiments aimed at elucidating the mechanism are relatively low,[6] and obviously the experimental results do not support the hypothesis that the O-H group is the sole source of the hydrogen transferred. Results and discussion

• at the end of the first part of this series.[3] On the other hand, we proved that a similar 1,5-hydrogen shift in which the acetyl group would be implicated does not occur either (see below). The standard experiment (entry 1) performed without any source of deuterium serves to evaluate the natural

• abundance of 13C in compound 1c and to calibrate the deuterium measurements. A possible source of hydrogen could be an alcohol present as a contaminant in various solvents, therefore we chose to examine the effect of addition of methanol to the reaction mixture. When xanthate 1a was treated with Et3B/dry

Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate strategy

• Asunción Barbero,
• Francisco J. Pulido and
• M. Carmen Sañudo

Beilstein J. Org. Chem. 2007, 3, No. 16, doi:10.1186/1860-5397-3-16

• quenching with D2O undergoes deuterio-decupration introducing deuterium exclusively in the vinylic position C-2. As mentioned in the introduction, the use of lower order cuprates such as silylcyanocuprate 1 leads selectively to allylsilanes. Trapping of the intermediate vinylcuprate 2 with α,β-unsaturated