Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• that thermal cleavage of allylic C(sp3)–H bonds is possible without using highly basic organolithium or organomagnesium reagents (Grignard reagents) that react with ketones rather than deprotonating the allylic C(sp3)–H bonds. Based on the observed perfect branch selectivity, we propose the catalytic

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• involving highly polar nucleophilic reagents such as organolithium and organomagnesium compounds or aluminium hydrides, tetrahydropyranylation reactions are usually run in hydrocarbons, chloroalkanes or dipolar aprotic solvents [1][2][8][9][10][11][12][13][14][15], thus affording a paradigmatic example of

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• organolithium, organomagnesium, organozinc, and organochromium A, to facilitate addition reactions of appropriate carbon electrophiles such as aldehydes (Scheme 1, top) [1]. In contrast, π-electrophilic carbon-connected late transition metals B facilitate the carbometalation of carbon–carbon multiple bonds

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• readily prepared from the corresponding aryl nitriles and organolithium or Grignard reagents, while analogous N-substituted imines are nontrivial to synthesize because of sluggish ketone/amine condensation. As such, the present reaction would complement the N-arylimine-directed alkenylation. Results and

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• ester gave the corresponding aldehyde 45 which was then transformed into the α-fluoroenimine 47. This was selectively converted into the corresponding sulfinylamines using Grignard reagents to access (S)-amino acids 48, while addition of organolithium reagents gave (R)-amino acids. A sequence of N- and

• give the (Z)-monofluoroalkene 67 as a single isomer (dr > 95:5). Conversion of the ester into the corresponding Weinreb amide, followed by addition of an organolithium reagent gave the corresponding ketone 69. Four further steps gave the ring skeleton for the proline residue of 71, i.e., formation of

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• erythronolide B, this result indicates that the organocopper compounds undergo conjugate addition to nitrosoalkenes in much more selective manner as compared to organolithium and organomagnesium reagents. Later on, Weinreb and co-workers demonstrated that organocopper reagents smoothly react with α-chlorooximes

• other nitrosoalkene sources (see Scheme 1) in reaction with organometallic compounds is very limited. Thus, Seebach and co-authors reported the addition of organolithium reagents to O-silyl nitronates 58 leading to α-substituted oximes 59 (Scheme 20) [42]. It is likely, that upon treatment with

• organolithium reagent silyl nitronate 58 is deprotonated to give anion 60, which eliminates the silyloxy anion to form nitrosoalkene NSA12. Conjugate addition of the second equivalent of the organolithium compound furnishes oximes 59. However, oximes 59 are produced in rather poor yields. In 1996, Trost

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• , derived in two steps from literature-known ketone 72 [49], was converted to an organolithium compound which attacked the aldehyde to give the free alcohol 73 in 1:2.5 diasteroselectivity in favor of the undesired R-isomer of 73, which can be explained by the Felkin–Ahn model. For generation of only (S)-73

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• and not fully complete, also the subsequent reaction with CO2 was more sluggish in comparison to 3a,b what resulted in lower yields. The increased reactivity of 3a,b compared to 3c,d may be explained by the ability of the former to stabilize the intermediate organolithium species by chelation due to

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• Organic Chemistry, SB RAS, Acad. Lavrentjev Ave. 9, Novosibirsk, 630090, Russian Federation 10.3762/bjoc.13.69 Abstract Borates M[C6F5BF3] (M = K, Li, Bu4N) react with organolithium compounds, RLi (R = Me, Bu, Ph), in 1,2-dimethoxyethane or diglyme to give M[4-RC6F4BF3] and M[2-RC6F4BF3]. When R is Me or

• from M[C6F5BF3] (M = K, Li and Bu4N) to alkyl-, alkynyl- and aryltetrafluorophenyltrifluoroborates using the nucleophilic substitution with some organolithium compounds. The obtained results were compared with previously reported data [31][32]. Results Reactions with MeLi An addition of MeLi (1.5 equiv

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

•  1). The use of an integrated microflow system allowed the preparation of functionalized α-ketoamides by a three-component reaction between carbamoyllithium, methyl chloroformate and organolithium compounds bearing sensitive functional groups (i.e., NO2, COOR, epoxide, carbonyl) (Scheme 2). It should

• Yoshida reported another remarkable finding on the use of protecting-group-free organolithium chemistry. In particular, the flash chemistry approach was exploited for generating benzyllithiums bearing aldehyde or ketone carbonyl groups [20]. This reaction could be problematic for two reasons: a) the

• competing Wurtz-type coupling, (i.e., the coupling of benzyllithiums with the starting benzyl halides); b) the nucleophilic attack of organolithium species to aldehyde or ketone carbonyl groups (Scheme 3). The authors reported that the extremely fast micromixing avoided undesired Wurtz-type coupling [21][22

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• described in Scheme 1, the nature of the medium and the substrate strongly influence the course of the reaction. Then, in the absence of a proton source, the organolithium intermediate can cyclize or react with an electrophile giving the expected coupling products [23][24][25][26][27]. Metal dissolving

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• unwanted possible side reaction pathways suggested by the analysis. The introduction of a single carbon atom in a ring in a nucleophilic sense may be achieved using dilithiomethane [133][134][135], tris(phenylthio)methyllithium [136], other reagents using established organolithium chemistry [137][138][139

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• , Grignard and organolithium reagents or ester enolates, the Weinreb amides can be easily converted into aldehydes, ketones, and β-keto esters, respectively [13][14][15][16][17][18][19][20]. Therefore, the transformation of β-amino Weinreb amides can provide a promising pathway towards the achievement of β

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• literature, however, to our knowledge this is the only such reaction reported with an aromatic amide [31]. Organolithium reagents have been used to synthesise the analogous alkylated DHQ compounds [27]. Compounds 21 and 22 were found to undergo slow degradation (over 2–4 weeks), as indicated by the

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• oxidative nucleophilic substitution for hydrogen reactions (ONSH) with organolithium or magnesium species or in vicarious nucleophilic substitution reactions (VNS) with carbon, oxygen or nitrogen nucleophiles [29]. VNS is a very powerful process for selective alkylation, amination and hydroxylation of

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• . (Note: In contrast, there have not been any rhodium-catalyzed CA reactions of alkyl nucleophiles.) Finally, (3) no 1,2-addition is observed in the rhodium variant because the organometallic reagents that are used are less reactive than the organolithium and -magnesium reagents used in the copper

Microsolvation and sp²-stereoinversion of monomeric α-(2,6-di-tert-butylphenyl)vinyllithium as measured by NMR

• Rudolf Knorr,
• Monika Knittl and
• Eva C. Rossmann

Beilstein J. Org. Chem. 2014, 10, 2521–2530, doi:10.3762/bjoc.10.263

• pair intermediate; monomeric alkenyllithiums; pseudoactivation parameters; sp2-stereoinversion mechanism; THF catalysis; Introduction Organolithium compounds tend to aggregate in solution unless the structure of their carbanionic part favors the nonaggregated (monomeric) species [2]. For example

• organolithium compound that does not carry heteroatoms X as possible donor ligands for an intermolecular coordination (such as C–Li–X). The frequency intervals of this 1:1:1 triplet are numerically equal to the magnitude of 1JC,Li which can reveal the degree of microsolvation via Equation 1: Decreasing (but

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• result of the reaction between bis(diethylamino)alkylphosphine 6 and ephedrine, followed by protection with borane. The subsequent stereoselective ring opening of compound 7 with an organolithium reagent gives way to acyclic products 8 with retention of configuration at the phosphorus center. These

• of different starting oxazaphospholidine borane complexes 7 from (−)-ephedrine or (+)-ephedrine [38] or by starting from the same oxazaphospholidine borane adduct 7 and then changing the order of addition of the organolithium reagents (Scheme 2). Acidolysis with HCl of compounds 8a results in the

• ]. Reaction of organometallic reagents with halophosphines The reaction of an organometallic reagent with the P-atom of halophosphines is a classical method used for the synthesis of both alkenyl- and arylphosphines. The organometallic reagents are mostly Grignard reagents [136][137][138] or organolithium

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