1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• 21 cannot be lithiated to give a stable vinyllithium species, and immediately expel a sulfide anion to afford phenylthioacetylene (Scheme 6a) [40], Brandsma showed that the lithiated derivatives of 1,4-dithiin (3) can be generated by ‘ortho-lithiation’-type reactions at −110 °C in THF (Scheme 6d) [41

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• the Ortiz group investigated the directed ortho-lithiation of aminophosphazenes, they realized one example synthesis of (R)-1-phenyl-2-((R)-1-phenylethyl)-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxide (239) from methyl (R)-(diphenyl((1-phenylethyl)amino)-λ5-phosphanylidene)carbamate (237) via the

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• subsequent reduction of the anthraquinone gave 1,4-difluoroanthracene. After ortho-lithiation and reaction with phthalic anhydride a carboxylic acid was obtained whose Friedel–Crafts acylation and subsequent reductive removal of the oxygen-functionalities resulted in the formation of the target compound. The

• HOMO–LUMO gap of 6,13-difluoropentacene was determined via UV–vis spectroscopy and compared to other fluorinated pentacenes. Keywords: fluorinated acenes; Friedel–Crafts reaction; ortho-lithiation; synthesis; Introduction Pentacenes are a prototype in the field of organic semiconductors due to their

• acid precursor could be prepared by reaction of the anthracenyllithium 7 with phthalic anhydride (8). Intermediate 7 could be accessed by ortho-lithiation of anthracene 9. The synthesis of 9 by two consecutive Friedel–Crafts acylation reactions and reduction of the resulting anthraquinone could start

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• dimethylamine or, by using ferrocenyl(dimethylamino)acetonitrile. The phosphine group is introduced by ortho-lithiation of the ferrocenylamine followed by subsequent trapping with chlorophosphine [114][115]. Preceding the ground breaking work by Pfaltz, many P,N ligands have been prepared for asymmetric

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• triptolide (Figure 2, route I and Scheme 7) [74]. In this synthesis, commercially available 2-isopropylphenol (31) was used as starting material, protection of 31 with chloromethyl methyl ether (MOM), followed by ortho lithiation and methylation with iodomethane, provided intermediate 85, which was lithiated

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• anion with the two hydroxy groups of the calixarene ligand to selectively direct the nucleophile towards one carbon atom of the π-allyl intermediate in the presence of potassium cations. In 2009 and 2010, Arnott et al. utilized a chiral isopropyloxazoline as an ortho-lithiation directing group in order

• selectivity of ortho-lithiation could be tuned by changing the alkyllithium reagent employed. The performance of four inherently chiral bidentate calix[4]arene ligands in the asymmetric Tsuji–Trost allylation reaction (Scheme 10) has been evaluated and compared to that of the planar model ligands. Inherently

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• been few reports on the preparation of fluoroalkyl phthalides [11][12][13][14][15][16][17][18][19]. The first synthesis of 3-(trifluoromethyl)phthalides was accomplished by Reinecke and Chen in 1993. They studied ortho-lithiation of phenyloxazolines and the subsequent reactions with pentafluoroacetone

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• electron-enriched arenes [7][8][9], diazotization/halogenations of anilines [10], and ortho-lithiation/halogenations sequence [11] among others are widely used as traditional strategies for creating C–X bonds. However, one or more problems such as poor site-selectivity, reliance on toxic halogen sources

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

• followed by reductive epoxide opening furnished the desired alcohol 73 [72]. Alcohol-directed 1,4-reduction using LiAlH4 [73] followed by ether formation gave methyl ether 74. Reduction of the remaining ketone moiety gave the equatorial alcohol exclusively. Ortho-lithiation followed by the addition of

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• Scheme 1. Surprisingly, no satisfying synthetic procedure for compound 4a was available from literature, but ortho-lithiation of veratrole (5) followed by treatment with trifluorosulfonyl chloride and triethylamine gave acceptable yields (47%). Conversion of 4-aminoveratrole (6) into the corresponding

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• intermediates that can be converted into various types of chiral ferrocene derivatives through diastereoselective ortho-lithiation [21]. Some years ago, the concept of flash chemistry was proposed, involving fast chemical synthesis by using flow microreactors, which enabled the use of highly reactive

Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

• Satoshi Takebayashi,
• Tsubasa Shizuno,
• Takashi Otani and
• Takanori Shibata

Beilstein J. Org. Chem. 2012, 8, 1844–1848, doi:10.3762/bjoc.8.212

• ]. Planar chiral 1,2-disubstituted ferrocene derivatives are usually synthesized by using diastereoselective ortho-lithiation of monosubstituted ferrocenes with an appropriate chiral ortho-directing substituent such as chiral amines, sulfoxides, and oxazolines [3]. However, this method suffers from low atom

• reactivity. The absolute configuration of planar chirality in 3c was determined to be S by X-ray crystallography (Figure 1). The absolute configuration is consistent with the previous report of diastereoselective ortho-lithiation of 1b [27]. Conclusion In conclusion, a Cp*Rh(III)-catalyzed reaction between

On the control of secondary carbanion structure utilising ligand effects during directed metallation

• Andrew E. H. Wheatley,
• Jonathan Clayden,
• Ian H. Hillier,
• Alison Campbell Smith,
• Mark A. Vincent,
• Laurence J. Taylor and
• Joanna Haywood

Beilstein J. Org. Chem. 2012, 8, 50–60, doi:10.3762/bjoc.8.5

• approaches the reactive position (“ortho lithiation” when deprotonation occurs adjacent to the directing group [2][3], “directed remote metallation” when reaction is non-adjacent [12][13][14][15]). However, the presence of substituents at the ortho position of the aromatic ring introduces the possibility of

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• regioselective functionalization. Ortho-lithiation by means of alkyllithium and lithium amides bases has been extensively developed as lithiated species display a high reactivity towards many electrophiles, leading to various substitutions (e.g., halogenation, carboxylation, acylation, hydroxymethylation

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• reactions: The benzyne precursor 2a and Schöllkopf’s bislactim ether 1 were allowed to react with 2.5 equivalents of sec-butyllithium at –95 °C to carry out the required ortho-lithiation for benzyne formation from 2a and the deprotonation of bislactim 1. During warming to room temperature, fragmentation to

• publication, we demonstrated the scope of the methodology over a range of ortho-lithiation benzyne precursors. To establish that any one of these precursors could be used to form quaternary adducts, we subjected the benzylation conditions to precursor 2b and the allylation conditions to precursor 2c

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• undergo ortho-lithiation [30], reaction of the tetralithio intermediate 8 with dimethyldichlorosilane led to the formation of the bis(siloxane) 19 (not the 5-membered ring bis(siloxane) isomer), whose structure was unambiguously confirmed by X-ray crystallographic analysis (see Scheme 2, inset). As

Selectivity in C-alkylation of dianions of protected 6-methyluridine

• Ngoc Hoa Nguyen,
• Christophe Len,
• Anne-Sophie Castanet and
• Jacques Mortier

Beilstein J. Org. Chem. 2011, 7, 1228–1233, doi:10.3762/bjoc.7.143

• coordination [19][20]. Primary, allylic, and benzylic halides usually give good yields of laterally alkylated products. Secondary and acetylenic halides have been used in several instances. Successful reaction with these substrates is noteworthy since many aryllithiums arising from ortho-lithiation reactions

Lithium phosphonate umpolung catalysts: Do fluoro substituents increase the catalytic activity?

• Anca Gliga,
• Bernd Goldfuss and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2011, 7, 1189–1197, doi:10.3762/bjoc.7.138

• ). The synthesis of diol 1 was conducted by an ortho lithiation of 1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-ol and subsequent addition of the in situ generated carbanion to formaldehyde. For comparison, a nonfluorinated diol precursor 2 was synthesized. Diol 3 was used as the precursor to investigate the

• nine ring phosphonates. The synthesis of these diols was realized by a double ortho lithiation of biphenyl and subsequent addition to the corresponding carbonyl compound. By this procedure, two asymmetric carbon centres and a chiral axis, which is fixed by intramolecular hydrogen bonds (6

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• up. Alternative routes to such trisubstituted benzenes include directed ortho-lithiation of 1,3-disubstituted benzenes followed by trapping of the anion with a nitrogen electrophile [63]. As a result a new route to access the key building block has been proposed which makes use of a less widely

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

• ]. More recently, Modro et al. reported a similar ortho-lithiation followed by [1,3]-shift of a phosphonyl group (6→7, Scheme 2) [18]; related processes have been observed with diazaphospholidine oxides [19] and bicyclic phosphoric triamides [20]. Benzylic lithiation-induced N- to C-[1,2]-anionic

Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• vinyl bromides 24a and 24b in good yields, respectively (Scheme 7). Vinyl bromide 24a was then subjected to lithiation with t-BuLi, followed by a CO2 quench. The desired carboxylic acid recovered from this reaction was only formed in low yields possibly due to issues with competing directed ortho

• -lithiation [25]. Notwithstanding, this acid was transformed into the corresponding methyl ester 25 using a Steglich-type esterification. Alkenyl reduction of the α,β-unsaturated ester under standard conditions gave the product of hydrogenation as an undetermined 3:1 mixture of diastereoisomers. The likely

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• by sulfinyl-directed ortho lithiation with n-butyllithium followed by reaction with tosyl azide. The resulting azo[2.2]paracyclophane was reduced in situ to give the amine (Rp,RS)-8 in good yield for the two steps (Scheme 2). Trichlorosilane-mediated deoxygenation proceeded uneventfully to furnished