Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• modified Appel reaction [17]. The alkynes H can be protected by silylation (J) because only primary alkynes react in the CuAAC (Figure 3). The synthesis commences with 4-hydroxypiperidine (1), which was converted to piperidine-4-one 3 bearing a protected alkyne moiety as well as to piperidin-4-one 5 with a

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

• (96% ee) despite using the same procedure as for the reaction between (S)-(+)-5 and PBr3. In addition, bromination of (S)-(+)-5 under Appel reaction conditions employing tetrabromomethane (CBr4) as a halide ion source used along with triphenylphosphine (Ph3P) was also investigated. Although this

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• Information File 658: Experimental part. Acknowledgements The authors wish to thank Dr. Bettina Appel and Julia Drenckhan for RNA synthesis service.

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

• halogenated products in high yields after simple purification. The polymer-supported triphenylphosphine oxides formed as a byproduct during these reactions could be recovered and reused numerous times with no appreciable decrease in reactivity. Keywords: Appel reaction; halogenation; organophosphorus

• reactions, such as those illustrated in Scheme 2: (1) the conversion of alcohols 4 to alkyl halides 5 (the Appel reaction), (2) the conversion of aldehydes 6 to 1,1-dihaloalkanes 7, (3) halogenation of aziridines 8 to form 2-haloamines 9, (4) halogenation of epoxides 10 to form 1,2-dihaloalkanes 11, (5) and

• processes in which the role of 1 is referred to as that of a catalyst [8][9][10][11][12]. For example, catalytic Appel reactions were achieved by slowly adding separate solutions of oxalyl chloride and alcohols 4 to a solution of 1 (Scheme 3) [8][9]. In these reactions, the simultaneous slow addition of

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• both alcohols showed a diastereomeric purity of >99% by 1H NMR. Mitsunobu reaction on the secondary alcohols using DEAD or DIAD did not provide the desired azides [42][43] nor did a one-pot Appel reaction/nucleophilic substitution/Staudinger reaction protocol involving a double inversion of

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

• to provide sufficient substance amounts for clinical tests [41][42]. Additionally, alternatives in reactions driven by the formation of phosphine oxides from phosphines (e.g. the Appel and Mitsunobu reaction) are highly desired to improve atom economy (reduced waste amounts) and to circumvent

• phase of the products 9 resulting in the crude diols 9a–d in a circa 90% purity according 1H NMR. Hence, the crude amino alcohols 9 were not further purified before the following cyclodehydration. Synthesis of cis-piperidinols B Cyclodehydration of amino alcohol syn-9a to piperidinol cis-11a under Appel

• MHz). Nevertheless, even with 4 equivalents of Selectride conversions of only up to 80% were observed. Unfortunately, subsequent Appel reaction of the diol anti-9a (dr = 25:1), synthesized through L-Selectride reduction in THF/CH2Cl2 (Table 4, entry 6), gave piperidinol 11a in a significantly

Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• . Synthesis of the monofluorinated pre-catalyst 8 (Scheme 2) commenced with an Appel reaction of alcohol 15 to prepare the primary bromide 18. Owing to the potentially labile nature of the primary bromide, this material was used without further purification in the next step. Reduction (H2, Pd/C) furnished the

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• stereospecifically the corresponding piperidone 4 in 80% yield. Subsequent bromination with CBr4 in the presence of PPh3 (Appel reaction) gave 5 in 84% yield. Finally, deprotection with 1 M SnCl4 in dichloromethane then neutralization by using K2CO3 afforded the final product (−)-epimyritine in a 80% yield. N-Cbz

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• possible to perform the Appel reaction using the same monolith and the relationship between the mechanisms of the two reactions is discussed. Keywords: bromination; flow chemistry; Ramirez gem-dibromoolefination reaction; solid-supported reagent; triphenylphosphine monolith; Introduction The advantages

• -Wittig and Appel reactions in flow [37][38][39][40]. The immobilisation of triphenylphosphine in this manner allowed the facile production of a collection of pure compounds using flow chemistry technologies with no need for further offline purification. Following the successful application of this

• monolith to the Appel reaction (the transformation of alkyl alcohols to the corresponding bromides), we wished to investigate the application of this monolith to the closely related Ramirez gem-dibromoolefination reaction; the formation of gem-dibromoolefins from aldehydes or ketones. In 1962 Ramirez

Bromination of hydrocarbons with CBr₄, initiated by light-emitting diode irradiation

• Yuta Nishina,
• Bunsho Ohtani and
• Kotaro Kikushima

Beilstein J. Org. Chem. 2013, 9, 1663–1667, doi:10.3762/bjoc.9.190

• useful bromide-containing precursors. For instance, alkyl alcohols can be converted to alkyl bromides in the presence of CBr4 and triphenylphosphine; this is known as the Appel reaction [28]. This combination can also be used to transform aldehydes into dibromoalkenes, which are useful precursors for the

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• product arising from cyclization onto the more distant double bond not detected [56]. We set out to access 55 from deprotonation of methyl ketone 57 on the less hindered side and alkylation with bromide 56. The E-allylic bromide was prepared rapidly, albeit in modest yield, with an Appel reaction [57] of

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• transformed under controlled conditions into the corresponding iodides [25]. The preparation of compound 7 can be also achieved by the transformation of alcohol 2 in an Appel-type reaction, circumventing the problems encountered during the Finkelstein reaction. Conversion of 7 with silver tosylate proceeded

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• thiols in a one-pot two-step reaction sequence mediated by Appel reagent (carbon tetrabromide and triphenylphosphine). 1,2-trans-Thioglycosides and β-glycosyl thiol derivatives were stereoselectively formed by the reaction of the in situ generated glycosyl bromides with thiols and sodium

• carbonotrithioate. The reaction conditions are reasonably simple and yields were very good. Keywords: Appel reagent; carbon tetrabromide; glycosyl hemiacetal; glycosyl thiol; thioglycoside; triphenylphosphine; Introduction Thioglycosides (1-thiosugar) are widely used glycosyl donors in glycosylation reactions [1

• extension of the earlier report [43], it was envisioned that the treatment of a stable glycosyl hemiacetal derivative with Appel reagent (carbon tetrabromide (CBr4) and triphenylphosphine (PPh3)) [44] could generate the glycosyl bromide in situ, [45][46] which, on reaction with thiol or sodium

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• azaphosphole was reported by Arbuzov and co-workers [10]. Subsequently, pioneering work by the research group of Appel established several interesting features associated with the DA reactions of phosphaalkenes [11][12]. Mathey and co-workers showed that 1H-phospholes underwent a 1,5-H shift followed by

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• were very likely formed by deprotonation at the benzylic position and subsequent elimination. Finally, freshly prepared unpurified 28 was subjected to the conditions of an Appel reaction [61] providing, after 16 hours at room temperature, pyrrolidine derivative 30 in 33% yield. Again, the relatively

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• treated with a reagent combination of CBr4 and Ph3P (Appel–Lee reagent) in either CH2Cl2 or DMF solvent, or a mixture of the two (Scheme 1). For the reaction in CH2Cl2, N,N,N’,N’-tetramethylurea (TMU) is added after in situ formation of α-glycosyl bromide 2, which equilibrates with a more reactive β

• -conformers of gt and gg (gt > gg >> tg), while the head moiety takes three conformers in averaged populations (gt = gg = tg). An established synthetic pathway to α-glycosyl-sn-glycerols 4a and 5a. A reagent combination of CBr4 and Ph3P (Appel–Lee reagent) is utilized in either CH2Cl2 or DMF as solvent

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

• 2NY, UK 10.3762/bjoc.7.194 Abstract Herein we describe the application of a monolithic triphenylphosphine reagent to the Appel reaction in flow-chemistry processing, to generate various brominated products with high purity and in excellent yields, and with no requirement for further off-line

• purification. Keywords: Appel reaction; bromination; flow chemistry; solid-supported reagent; triphenylphosphine monolith; Introduction Flow chemistry is well-established as a useful addition to the toolbox of the modern research chemist, with advantages accrued through increased efficiency, reproducibility

• application of this monolith to the transformation of an alkyl alcohol into the corresponding alkyl bromide by using carbon tetrabromide in the Appel reaction. In the 1960s Ramirez and co-workers reported the formation of a phosphine–methylene species when triphenylphosphine was mixed with carbon tetrabromide

Synthesis of the fluorescent amino acid rac-(7-hydroxycoumarin-4-yl)ethylglycine

• Manfred Braun and
• Torsten Dittrich

Beilstein J. Org. Chem. 2010, 6, No. 69, doi:10.3762/bjoc.6.69

• treatment with tert-butyl(dimethyl)silyl chloride gave alcohol 4 in 59% yield after removal of the doubly silylated side product the formation of which could not be completely avoided. By means of an Appel reaction [15], the alcohol 4 was converted into the bromide 5 in 79% yield. In the following key-step

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• reaction with lithium cyclohexyl(isopropyl)amide (LCIA) in 49% overall yield for the 4-step sequence. The elaboration of intermediate 27 entailed a protection-deprotection maneuver that prepared the molecule for an ultimate Appel reaction [28] as a way to install the iodo substituent. The second key