A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• -supported benzotriazole [7] with arylmagnesium reagents, addition of phenyllithium to selenoamides [8], addition of organometallic species [9][10][11][12][13][14][15][16][17][18][19][20][21] or arylboronic acids [22][23][24][25][26][27] to imines, reaction of organolithium and Grignard reagents with

Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• ’-deoxycytidine) as a starting material for the envisioned transformations (Scheme 2). To the best of our knowledge, the addition of organometallic compounds (organolithium and organomagnesium, etc.) to aldehyde 1 is not described in the literature. Compound 1 was readily converted to 5hmC analogues 2a–e by

• treatment with various Grignard reagents (methylmagnesium bromide, THF, 0 °C → room temperature, or vinylmagnesium bromide, THF, 0 °C → room temperature) and organolithium reagents (lithium (trimethylsilyl)acetylide, THF, −40 °C → −20 °C or lithium phenylacetylide, THF, −78 °C → −50 °C) (Scheme 2). These

• treatment of aldehyde 1 with β,β,β-trichloro-tert-butoxycarbonyl chloride (TCBocCl) [31] in the presence of pyridine in DCM (Scheme 3). The reaction of 4 with Grignard (methylmagnesium bromide, THF, 0 °C → room temperature, or vinylmagnesium bromide, THF, 0 °C → room temperature) and organolithium reagents

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• desired dehalogenated dihydropyrrole with 66% yield (formula not shown). For the conversion of 19 to 20, we applied a bromine–lithium exchange with 2 equivalents of t-BuLi in diethyl ether at –90 °C [71], followed by hydrolysis. Even though oxazolidines are known to be sensitive towards organolithium

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

• rearrangement to set the geometry of the γ,δ-unsaturated double bond. In the forward direction, the allylic alcohol 44 was obtained from reaction of the alkenyllithium reagent derived from 2-bromopropene with phenylacetaldehyde (Scheme 10). In our hands, the organolithium afforded significantly higher and more

Ring-opening reaction of 2,5-dioctyldithieno[2,3-b:3',2'-d]thiophene in the presence of aryllithium reagents

• Hao Zhong,
• Jianwu Shi,
• Jianxun Kang,
• Shaomin Wang,
• Xinming Liu and
• Hua Wang

Beilstein J. Org. Chem. 2013, 9, 767–774, doi:10.3762/bjoc.9.87

• . To construct DTT functional materials, deprotonation of DTT with organolithium reagents seems to be one of the most important approaches. However, the ring-opening reaction of DTT leading to the cleavage of the center ring can be observed in the presence of n-BuLi. In our previous work, we reported

• , high selectivity towards the ring opening was observed with n-BuLi when compared with other organolithium reagents. However, most of these ring-opening reactions mentioned above take place by using n-BuLi as the nucleophile to attack the sulfur atoms of thiophenes. Other organolithium reagents have

• rarely been employed for this kind of reaction. Furthermore, the relationship between the nucleophilicity of organolithium reagents and the efficiency of the ring opening of fused thiophenes has not been discussed. In this paper, we present the ring opening of 2,5-dioctyldithieno[2,3-b:3',2'-d]thiophene

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• incorporating an α-aryl substituent, we show that they will also undergo attack at the β-carbon by organolithium nucleophiles, leading to the products of carbolithiation. The carbolithiation of E and Z N-alkenyl ureas is diastereospecific, and N-tert-butoxycarbonyl N-alkenyl carbamates give carbolithiation

• products that may be deprotected in situ to provide a new connective route to hindered amines. Keywords: carbamate; carbolithiation; carbometallation; organolithium; stereospecificity; styrene; urea; Introduction Enamines and N-acyl enamines are in general nucleophiles, reacting with electrophiles at the

• reversed when N-acylenamines (especially N-vinyl ureas [8]) meet organolithium nucleophiles. N-Carbamoyl enamines bearing α-aryl substituents (in other words, α-acylaminostyrenes), may undergo reaction as electrophiles, with the carbon atom β to nitrogen succumbing to attack by organolithium nucleophiles

Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer

• William F. Bailey and
• Justin D. Fair

Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59

• a variety of functionalized carbocyclic [5][6][7] and heterocyclic systems [8][9]. The bonding changes that accompany cyclization of an unsaturated organolithium indicate that the process should be energetically favorable since a σ-bond (bond energy ca. 88 kcal/mol) is generated at the expense of a

• formal [1,4]-proton transfer as depicted in Scheme 5. Cyclization of 3 quickly generates the monocyclic product and a second cyclization gives the endo-5-methyl-2-methylene organolithium 7 in nearly 90% yield. However, a proton transfer to give the more stable allylic anion apparently foils the final

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• [26] nucleophiles, and oxidative nucleophilic substitution of hydrogen (ONSH) with Grignard and organolithium reagents [27]. This chemistry significantly expanded the range of available SF5-benzene derivatives. The synthetic chemistry and biological activity of pentafluorosulfanyl organic molecules

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

• the possibility of introducing further functionalization on the molecule by trapping the reactive organolithium intermediates with electrophiles. Keywords: alkenes; asymmetric synthesis; carbolithiation; carbometallation; enantioselectivity; lithium; Introduction The carbolithiation reaction has

• attracted considerable interest among synthetic organic chemists, as it offers an attractive pathway for the efficient construction of new carbon–carbon bonds by addition of an organolithium reagent to nonactivated alkenes or alkynes, with the possibility of introducing further functionalization on the

• molecule by trapping the reactive organolithium intermediates with electrophiles. Several reviews have covered the synthetic applications of this kind of reaction [1][2][3][4][5][6][7][8]. When alkenes are used, up to two contiguous stereogenic centers may be generated, which may be controlled by using

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• involving polar intermediates and/or transition states has been investigated on a broad scale for the first time. The reactions studied include lithiation, reaction of the thus formed organolithium salts with various electrophiles (among others, allyl bromide, DMF and acetone), oxidation to cyclopentenones

• Scheme 6 all of these experiments failed. Neither could we prepare the “coupling product” 27 by treatment of 4 with the biselectrophile dimethylysilyl dichloride nor the dimer 28 by the direct action of iodine on the organolithium compound 4. In this latter case we noted after work-up and GC–MS analysis

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• formal synthesis of the anti-dyskinesia agent sarizotan, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions. Keywords: carbolithiation; carbometallation; dihydropyridines; organolithium reagents; pyridines; sarizotan

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• the tetramethylbutadiene 22 is first dibromocyclopropanated to the tetrabromide 23, which, on treatment with an organolithium reagent, is debrominated/rearranged to the target hydrocarbon 24. Hydrocarbon 24 is a stable colorless solid that can be worked with under normal laboratory conditions without

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• Cy3P did not lead to the orange–red colouration suggestive of ylide formation, and only starting epoxide 11 was observed. We also studied the possibility of generating alcohol 7 from terminal epoxide 11 using an organolithium instead of a hindered lithium amide as the base (Scheme 5). Organolithiums

• , in particular secondary and tertiary organolithiums, are known to react with terminal epoxides by α-lithiation, although this is typically followed by trapping of the α-lithiated epoxide with a second equivalent of the organolithium and elimination of Li2O to give an E-alkene (e.g., 12): a process

Synthesis of oleophilic electron-rich phenylhydrazines

• Aleksandra Jankowiak and
• Piotr Kaszyński

Beilstein J. Org. Chem. 2012, 8, 275–282, doi:10.3762/bjoc.8.29

• accessible DTBAD through the organolithium. Although we focus on long-chain-substituted phenylhydrazines, we believe that this method can be used for other electron-rich arylhydrazines. Experimental Reagents and solvents were obtained commercially. Reactions were carried out under Ar. 1H NMR spectra were

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• ; nothapodytine; organolithium compounds; topopyrone; Review Our laboratory is primarily interested in the total synthesis of natural products, and does not conduct research on directed aromatic functionalization ("DAF") per se. On numerous occasions, however, DAF technology has been key to the success of

• through the union of fragments 56 or 57 with aldehyde 58: The carrier of a moiety that is common to all topopyrones. A serviceable form of 58 proved to be compound 65, the preparation of which is outlined in Scheme 12. A key step in this sequence was the addition of the organolithium species 60, obtained

• benzamide 56 with sec-BuLi/TMEDA (1.05 equiv, 3 h, −78 °C) and addition of the resulting organolithium agent to 65 was presumed to form the alkoxide 66. In situ treatment of 66 with t-BuLi induced bromine–lithium exchange and cyclization of organolithium species 67 to a product that was believed to be 68

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• organolithium compounds having varying degrees of configurational stability [17][18], and in our studies on ureas and amides we were able to identify correlated inversion processes linking configurational inversion at organolithium centres with conformational inversion of atropisomeric chirality by bond

• of the resulting organolithium returned the product 7 in up to 88% yield as a mixture of diastereoisomers (by NMR). Previous data on the conformational stability of related diaryl ether [10], coupled with our inability to separate these diastereoisomers, and the invariant ratio in which they were

• which the minor organolithium is rapidly converted to product, followed slowly by the major organolithium [28]. Hoppe observed a related effect in the alkylations of cinnamyllithiums [29]. Previous results from the laboratories of Hoppe indicated that lithiated O-benzylcarbamates are typically

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

• addition of organolithium reagents to arene tricarbonylchromium complexes [7] and α,β-unsaturated aldimines [8]. Notably, derivatives of hydrobenzoin in which the aromatic rings have been functionalized in the ortho and ortho' positions often display improved diastereo- or enantioselectivity over the

• reaction conditions [23]. Notably, addition of TMEDA (entries 3 and 5), which would presumably assist in the disaggregation of organolithium species, failed to improve these results and in fact led to lower conversion and isolated yields of the diiodohydrobenzoin 12. During the evaluation of the reaction

Bromine–lithium exchange: An efficient tool in the modular construction of biaryl ligands

• Laurence Bonnafoux,
• Frédéric R. Leroux and
• Françoise Colobert

Beilstein J. Org. Chem. 2011, 7, 1278–1287, doi:10.3762/bjoc.7.148

• ). Results and Discussion Regioselective bromine–lithium exchange on polybrominated biphenyls Our group recently reported the efficient coupling of organolithium intermediates with arynes, the so-called "ARYNE coupling" [25][31][36]. This protocol is based on the formation of a thermodynamically stable

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• capable of selectively abstracting hydrogen from organic substrates continues. Routinely, organolithium reagents have been employed for this purpose with the high electropositivity of lithium affording polar, reactive Cδ−–Liδ+ bonds proficient in metallating C–H bonds in organic, especially aromatic and

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

• Li2CuCl4 [16][17][18] to 11 followed by quenching with 4-bromobut-1-ene failed to produce 3a. Consequently, lateral lithiations were examined. Lateral lithiation of benzenoid aromatics requires a stabilizing group capable of either delocalizing negative charge or stabilizing an organolithium by

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• inter- or intramolecularly [8][9][10][11][12][13][14][15][16]. However, an increased range of aromatic moieties can be introduced through the use of organometallic compounds. The most commonly employed reagents are organoindium [17][18], organolithium [19][20], organomagnesium [21][22], organotin [23

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

• , allylic ethers derived from cyclopropenyl carbinols were selected as substrates. Cyclopropenyl carbinols have recently emerged as synthetically useful building blocks [39] and are readily available by the condensation of an in situ generated cyclopropenyl organolithium with an aldehyde [39][40

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

• medicinal chemistry, surprisingly few effective methods are suitable for the asymmetric synthesis of tertiary thiols. This review details the most practical of the methods available. Keywords: asymmetric synthesis; organolithium; sulfur; substitution; thiol; Introduction Organosulfur compounds play key

• )-thiolactomycin (66) in >99:1 er. 2.2 Electrophilic attack on α-thioorganolithiums Formation of carbon–carbon bonds adjacent to heteroatoms by deprotonation with an organolithium base and subsequent reaction with an electrophile has become an important and versatile method, especially when chiral ligands may be

• presence of (−)-sparteine 74 (Scheme 26) were attempted [64]. Trapping the lithiated intermediate 75 with electrophiles gave products with poor enantioselectivities, but the results gave no indication of the configurational stability of the intermediate organolithium 75. To establish the factors governing

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

• substrate 1a (57%, Scheme 4) [28]. Initially, we examined organolithiums for their propensity to induce deprotonation-migration in N-phosphonate aziridine 1a. Despite it being previously noted by Zwierzak that the reaction of organolithium reagents with such substrates resulted in preferential attack at

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• behavior in their reactions with nucleophiles. For example, the reaction of CF3I with alkali gives fluoroform (CHF3) and potassium hypoiodide (KIO) [122]. The interaction of organolithium compounds with perfluoroalkyl iodides [123][124][125][126] does not result in combination of the two alkyl species (RF