The preferred conformation of erythro- and threo-1,2-difluorocyclododecanes

• Yi Wang,
• Peer Kirsch,
• Tomas Lebl,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2012, 8, 1271–1278, doi:10.3762/bjoc.8.143

• revealed that the CF2 groups always occupied corner positions. This was deduced by a combination of 19F NMR, X-ray structure analysis and theory studies. Two reasons emerged for this. Firstly, if a C–F bond did project into the ring (endo), then the increased size of the fluorine atom relative to hydrogen

• hyperconjugative interactions with the anti-periplanar C–H bonds, similar to that found in 1,2-difluoroethane in the well know gauche effect [10][11]. On the other hand, the erythro stereoisomer 5a would have a C–F bond projecting into the ring in an endo manner, if the vicinal fluorines were edge/edge located

• study examined whether the vicinal C–F bonds prefer to adopt corner/edge or edge/edge locations of the [3333] ring system. For each diastereoisomer it emerged that one of the C–F bonds adopts a corner location. The second orientates exo to the ring. When the C–F bond projects endo into the ring, the

Prins fluorination cyclisations: Preparation of 4-fluoro-pyran and -piperidine heterocycles

• Guillaume G. Launay,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2010, 6, No. 41, doi:10.3762/bjoc.6.41

• -piperidines were investigated. The products were obtained in good yields, but only with moderate diastereoselectivity. These Prins fluorination reactions can be accelerated under microwave conditions. The study extends the Prins fluorination methodology for the generation of the C–F bond in heterocycles

• . Keywords: 4-fluoropiperidine; 4-fluoropyran; heterocycles; organo-fluorine chemistry; Prins cyclisation; Introduction Selective incorporation of the C–F bond into organic molecules can impart useful and attractive properties to performance materials [1][2][3]. To this end there are a useful but relatively

• incorporated into the product generating a C–F bond and a new stereogenic centre. Liberation of fluoride ion from BF3·OEt2 has, for example, been observed in epoxide ring opening reactions [8][9]. This was first recognised in a Prins reaction as an unexpected side reaction by Al-Mutairi et al. [10][11] and was

Chemical aminoacylation of tRNAs with fluorinated amino acids for in vitro protein mutagenesis

• Shijie Ye,
• Allison Ann Berger,
• Dominique Petzold,
• Oliver Reimann,
• Benjamin Matt and
• Beate Koksch

Beilstein J. Org. Chem. 2010, 6, No. 40, doi:10.3762/bjoc.6.40

• the preparation of caged proteins. Fluorine is the most electronegative element and has a van der Waals radius of 1.47 Å [10]. Thus, substitution of a C–H bond with a C–F bond dramatically changes the electronic properties of the given molecule but exerts only a minor steric effect [11]. Due to the

• was treated with N-(4-pentenoyloxy)succinimide and in the second step treatment with iodoacetonitrile gave the desired compound in yields ranging from 59 to 81%. Due to the strong electron-withdrawing character of the C–F bond, the CF3 substituent in the α-position in α-(Tfm)Ala influences

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• conformational tool for the synthesis of shape-controlled functional molecules. This review will begin by describing some general aspects of the C–F bond and the various conformational effects associated with C–F bonds (i.e. dipole–dipole interactions, charge–dipole interactions and hyperconjugation). Examples

• ; stereoelectronic effects; Review General aspects of the C–F bond Fluorine is a small atom, with an atomic radius intermediate between that of hydrogen and oxygen (Table 1). The small size of fluorine means that it can be incorporated into an organic molecule as a replacement for hydrogen without dramatically

• affecting the overall molecular size. However, fluorine is the most electronegative element in the periodic table, consequently the C–F bond is highly polarised and in this sense it is a dramatic change from a C–H bond [1][2]. In the highly polarised C–F bond, the fluorine atom bears a partial negative

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

• Vincent A. Brunet,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2009, 5, No. 61, doi:10.3762/bjoc.5.61

• diastereoisomeric series of this motif. The route is a significant improvement on an earlier six step strategy. Keywords: C–F bond; organo–fluorine chemistry; stereospecific fluorination; vicinal trifluoro motif; Introduction Selective fluorination is an important strategy for the design of performance molecules

• in medicinal chemistry programmes and in organic materials [1][2]. To date arylfluorines have dominated this agenda. However molecules where the C–F bond is a constituent of a stereogenic centre are gaining in prominence, particularly as new reagents and more versatile asymmetric methods facilitate

• their syntheses [3][4]. The fluorine atom is small, with a steric impact only a little larger than hydrogen, and it is a weak hydrogen bond acceptor [4]. However the C–F bond is polar and thus interactions with nearby functional groups are largely a result of dipolar interactions rather than hydrogen

DBFOX- Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones

• Takehisa Ishimaru,
• Norio Shibata,
• Dhande Sudhakar Reddy,
• Takao Horikawa,
• Shuichi Nakamura and
• Takeshi Toru

Beilstein J. Org. Chem. 2008, 4, No. 16, doi:10.3762/bjoc.4.16

• electrophilic fluorination represents an important and straightforward strategy for C-F bond formation at a carbon stereocenter, providing easy access to chiral fluoro-organic compounds [1][2]. Due to the significance of chiral fluoro-organic compounds, such as fluorinated quinolones [3][4] and liquid crystals

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

• Frédéric R. Leroux,
• Baptiste Manteau,
• Jean-Pierre Vors and
• Sergiy Pazenok

Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13

• to methanol [46]. The geminally 1,1-difluorinated 2,3,4,6-tetra-O-acetyl-1-deoxy-D-glucopyranose (6, Figure 3) [47] exhibits unequivocally non-identical C-F bond lengths, according to crystallography. The difference of 1.5 hundredth of an Å falls in the expected range. 2,2,3,3-Tetrafluoro-2,3-dihydro

Single and double stereoselective fluorination of (E)-allylsilanes

• Marcin Sawicki,
• Angela Kwok,
• Matthew Tredwell and
• Véronique Gouverneur

Beilstein J. Org. Chem. 2007, 3, No. 34, doi:10.1186/1860-5397-3-34

• Selectfluor. These reactions proceeded with efficient transfer of chirality from the silylated to the fluorinated stereocentre. Upon double fluorination, an unsymmetrical ethyl syn-2,5-difluoroalk-3-enoic ester was prepared, the silyl group acting as an anti stereodirecting group for the two C-F bond forming

• events. Findings Asymmetric C-F bond formation continues to challenge chemists, inspiring the development of increasingly effective protocols for stereocontrolled fluorination. [1][2][3][4][5][6][7][8][9][10][11] Studies from our laboratory illustrated that allylsilanes undergo electrophilic

The vicinal difluoro motif: The synthesis and conformation of erythro- and threo- diastereoisomers of 1,2-difluorodiphenylethanes, 2,3-difluorosuccinic acids and their derivatives

• David O'Hagan,
• Henry S. Rzepa,
• Martin Schüler and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2006, 2, No. 19, doi:10.1186/1860-5397-2-19

• noticed a conformational presence in α-fluoroamides [29], where the C-F bond aligns anti and planar to the amide carbonyl as illustrated in Figure 10. This adds an additional conformational constraint to these amides with a barrier to rotation around the C(CO)-C(F) bond of around 7-8 kcal mol-1. The

• preference of the C-F bond in α-fluoroamides to align anti periplanar to the carbonyl bond can be rationalized in terms of C-F bond and amide dipole relaxation as well as N-H...F hydrogen bonding [30]. The solution and solid state structures of 2,3-difluorosuccinate benzylamides 22 have been evaluated. These

Stereoselective α-fluoroamide and α-fluoro- γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

• Kenny Tenza,
• Julian S. Northen,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2005, 1, No. 13, doi:10.1186/1860-5397-1-13

• fluorine at the stereogenic centre. Introduction The development of methods for the stereoselective introduction of the C-F bond, α-to a carbonyl group has been a significant and recent focus in organo-fluorine chemistry.[1][2] Most effort has involved enolate reactions with electrophilic fluorinating

• containing substrates gave higher diastereoselectivities relative to the non-fluorinated counterpart an observation which may have its origin in electronic stabilisation of one diastereoselective transition state as a consequence of the C-F bond. The aza-Claisen products where then subjected to