Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• using AgF2 as both oxidant and fluorine atom source via the silver(II)-mediated ring-opening and fluorination of cyclopropanols 91 (Scheme 32) [112]. Through this method, a fluorine atom could easily be introduced in the β-position of a ketone. The mechanism is outlined in Scheme 32, the Ag-alkoxide

A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety

• Ilya V. Taydakov,
• Yuliya M. Kreshchenova and
• Ekaterina P. Dolotova

Beilstein J. Org. Chem. 2018, 14, 3106–3111, doi:10.3762/bjoc.14.290

• evaporator, 60 °C, 5 Torr). The residue was pulverized in dry Ar atmosphere and dried at 0.05 Torr and 60 °C for at least 5 h. The quality of the alkoxide dramatically affects the yields of a β-diketone, while the stoichiometry is much less significant. The best results were achieved with commercial NaOMe or

• autocatalytic nature of the reaction. Since the alkoxide that is formed during the reaction acts as a catalyst [30], addition of small amounts (200–500 μL) of anhydrous EtOH (in a reaction using 100 mmol of compounds) to the initial NaH suspension in THF makes the reaction fully controllable. As it was

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• fission may also be used to generate different metal derivatives of the nucleofugal anions as equilibrium components. Fluoride-catalyzed, metal-free desilylation admitted carbonyl addition but blocked the retro-addition. Keywords: alkoxide fission; desilylation; fragmentation; retro-addition; reversible

• formally) heterolytic cleavage of C–C single bonds can provide cases of interest if it generates organometallic compounds under unusual conditions. The well-known cases of alkoxide fission [1][2][3] (top line of Scheme 1) may be viewed as a reversed formation of an alkoxide A1M1 from an organometallic C–M1

• and a carbonyl compound (R1)2C=O. Such a C–C fission (retro-addition reaction) can occur already near room temperature (rt) if the nucleofugal carbanion proves to be an electronically stabilized N≡C–CH2– [1] or allylic [2] species or a short-lived equilibrium component [3]. A cleavable alkoxide A1M1

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• alkoxide G that undergoes a [1,4]-shift of the silicon group with concomitant ejection of cyanide anion to form acyl cyanide H [33]. As the reaction is run in the presence of ethanol, nucleophilic acyl substitution of cyanide H for the ethoxy group furnishes the ethyl ester 21 in one pot. We were therefore

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• the optimum degree of fluorination of the alkoxide ligands for tungsten alkylidyne complexes [53][54]. It was found that the tungsten alkylidyne complex [MesC≡W{OC(CF3)Me2}3] (Figure 1, WF3) showed excellent catalytic performance not only in the metathesis of internal but also, for the first time with

• the metal tungsten, terminal alkynes at room temperature [54]. Our studies clearly display a strong dependency of the catalytic alkyne metathesis activity on the metal-alkoxide combination. The electrophilicity of the metal sites can be controlled by the number of fluorine atoms of the ancillary

• ]. Dinuclear Mo≡Mo complexes, however, have not yet been cleaved efficiently by alkynes [87]. Results and Discussion Complex synthesis The dimeric molybdenum complex [Mo2Cl6(dme)2] (dme = 1,2-dimethoxyethane) serves as an excellent starting material for compounds of the type Mo2X6 (X = alkyl, alkoxide) [73

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

• would lead to a low-valent allylcobalt(I) species, and then C–C bond formation of IV with 2a would proceed at the γ-position to produce cobalt alkoxide(I) V [28][29][31][32][33][34][35][36][37][38][39]. Transmetalation between V and AlMe3 would furnish branched aluminium alkoxide VI along with the

• regeneration of I. Alkoxide VI is converted to homoallylic alcohol 3aa by usual work-up. Conclusion In conclusion, we have successfully developed a cobalt-catalyzed nucleophilic addition of the C(sp3)–H bond of simple alkenes to ketones. This novel transformation could realize perfect branch selectivity for

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

• give the chromium alkoxide L [24]. Finally, the Cr–O bond is cleaved by TMSCl, generating the active chromium salt for the transmetalation and the silyl ether M, the desilylation of which with a fluoride anion results in the formation of a homoallylic alcohol 4. Conclusion The cobalt/chromium-catalyzed

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• solvent and appears to be selective for phenols; only two primary alcohol examples were produced in 63–67% yield in the presence of a strong base. A radical pathway from the alkoxide species was proposed by the authors as an explanation for the phenol selectivity under weakly basic conditions in the

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• complete oxidation with DDQ, has been successfully developed. Further transformation with alkylamine/sodium alkoxide alcohol solution conveniently afforded novel polysubstituted pyrroles in good to excellent yields. This methodology for highly functionalized pyrroles performed well over a broad scope of

• cycloaddition of azomethine ylides with N-alkyl maleimide, followed by a facile oxidation using DDQ as oxidant. Further manipulation with alkylamine/sodium alkoxide alcohol solution conveniently led to novel polysubstituted pyrroles in good to excellent yields (Scheme 1). Results and Discussion As shown in

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• underlying idea behind the latter application is that protonation of the leaving group by a general acid is not needed with 5´-thiosubstituted analogs, since the sulfide ion is a much better leaving group than the alkoxide ion. Most extensively used thiosubstitution, however, is replacement of either one of

• negative than the βlg = −1.28 of the hydroxide-ion-catalyzed reaction where the departing group is an alkoxide ion [49]. Accordingly, the departing oxygen atom seems to become protonated concerted with rate-limiting rupture of the P–OR bond. The essential mechanistic features, hence, are proton transfer to

• phosphorane that decomposes to 2´,3´-cyclic phosphate by departure of the 5´-linked nucleoside as an alkoxide ion (Scheme 3). The stability of the dianionic phosphorane has been studied by experimental and computational methods. As mentioned above, the βlg value of the reaction of uridine 3´-alkyl phosphates

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• leads to the formation of the corresponding magnesium acetal Int-D, (ii) the alkoxide attacks another ester carbonyl moiety in the molecule to form the corresponding 5-membered ring acetal intermediate (Int-E) [15][16][17], after which immediate hydrolysis leads to the exclusive formation of the

• chloride with the γ-keto ester 6 furnishes the corresponding magnesium alkoxide Int-F, which can be easily converted to the 5-membered ring intermediate, Int-G, as already discussed in the reaction of 7→6 (Figure 2b). However, the reaction at a higher temperature may lead to the elimination of MeOMgCl

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• role in promoting the reaction. Interestingly TsCl is prone to hydrolysis in the presence of water, yet it did not seem to affect the high reactivity observed with NaOH, likely because the generated, strongly nucleophilic, alkoxide would react even faster. Progress of reactions in entries 4 and 5 in

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• results were summarized in Table 1. For this purpose, evaluation was performed on the basis of the energetic difference between neutral compounds and the corresponding carbanion or alkoxide species: thus, in the former instance, ΔEC as E3X-C − E1X (or E4X-C − E2X) or the latter ΔEO as E3X-O − E1X (or E4X

• -O − E2X) in the case of propargylic (or allylic) alcohols, respectively, as the simple measure of destabilization. In the case of the non-fluorinated 1H and 2H series, as expected, a clear alkoxide preference was noticed irrespective of the carbon–carbon unsaturation pattern. For the corresponding

• the alkoxide 3F-Oa. In the case of 1Fb, the phenyl group worked nicely for increase of the energetic preference of 3F-Cb to 3F-Ob of about 7.9 kcal/mol. For the allylic alcohol 2Fb (R = Ph), although the ΔΔE value was small, the carbanionic species 4F-Cb was calculated to be more (or at least almost

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• equiv) with n-BuLi (1.1 equiv) at −50 °C in 10 mL PFA reactor with 7 min residence time. This lithium compound reacts with the ketone intermediate at 30 °C for 2 min in 5 mL PFA reactor coil. The intermediate lithium alkoxide is further reacted with trifluoroacetic anhydride (2 equiv) in a 10 mL PFA

• reactor will be similar to the previous reactor. This lithiated intermediate and the ketone intermediate obtained by the simultaneous process can be mixed using a ratio controller at the optimum stoichiometric amount. The obtained lithium alkoxide can be monitored inline using a suitable analytical

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• yield of 5d (22%). We speculated that the low yield was caused by the presence of an additional hydroxy group in 3b. The formation of the alkoxide anion on the substrate due to the thermodynamically unfavorable equilibrium with Cs2CO3 might promote the destruction of the anthraquinone scaffold. Indeed

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions

• David C. Marelius,
• Curtis E. Moore,
• Arnold L. Rheingold and
• Douglas B. Grotjahn

Beilstein J. Org. Chem. 2016, 12, 1334–1339, doi:10.3762/bjoc.12.126

• , Figure 2), a situation that would not be possible for a monomeric structure. Attempts to synthesize 5 using sodium alkoxide bases led to the formation of dimer structures 6 with presumed loss of NaCl. Therefore, lithium chloride adducts 7 were targeted because LiCl adduct 3 was isolable yet highly

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• chiral calcium alkoxide complex was generated in situ by mixing Ca(OEt)2, PyBox ligand (S,S)-88, and phenol 89. The authors found that the slow addition of malonate 86 and the use of phenol 89 and ethanol as additives were all crucial for achieving high yield and enantioselectivity, although the exact

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• alkoxide species C. Reductive elimination of species C gave the product and regenerated the active iridium catalyst. Recently, Qiu and co-workers developed a novel chiral ligand L5 based on a chiral-bridged biphenyl backbone and successfully achieved the asymmetric addition of arylboronic acids to N

• ] and PCy3 formed the ruthenium(0) complex, which then mediated the oxidative coupling of N-benzyl-protected isatin and styrene to form oxametallacycle I. The ruthenium alkoxide III was formed through two possible pathways: (a) the direct transfer hydrogenolytic cleavage of I (slow); (b) the

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• control with electrophilic quench by a variety of electrophiles. After evaluating a few chiral diamino-alkoxide ligands, ligand 24 was identified as a superior choice. As shown in Figure 7, the result was not optimal with only 30–75% of the desired α-substituted products being obtained and the

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• anion equivalent 3 is known as the "Breslow intermediate". Its reaction with another molecule of aldehyde leads to the formation of an alkoxide intermediate 4. Proton transfer and subsequent release of thiazolylidene 1 affords the final product, the α-hydroxy ketone 5. Breslow demonstrated that

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• intermediate mechanism is usually involved. The formation of an inclusion-complex first occurs and then the secondary alkoxide of the host pseudo-intramolecularly attacks the phosphorus atom to form a covalent bond. Finally an alkoxide ion could react with the formed phosphonates to regenerate the CD secondary

• alkoxide and to release the hydrolyzed product (Scheme 2). In 1970, van Hooidonk and Breebaart first studied the alkaline hydrolysis of the enantiomers of isopropyl methylphosphonofluoridate (sarin) with α-CD in aqueous solution at pH 9.0 and 25 °C. A hydrolysis rate enhancement is observed and they report

Polydisperse methyl β-cyclodextrin–epichlorohydrin polymers: variable contact time ¹³C CP-MAS solid-state NMR characterization

• Isabelle Mallard,
• Davy Baudelet,
• Franca Castiglione,
• Monica Ferro,
• Walter Panzeri,
• Enzio Ragg and
• Andrea Mele

Beilstein J. Org. Chem. 2015, 11, 2785–2794, doi:10.3762/bjoc.11.299

• conditions to achieve deprotonation of the hydroxyl groups. Then, EP reacts with the alkoxide to form intra- or inter-ether linkages. We previously proposed the synthesis [22] of soluble and insoluble polymers of a partially secondary rim methylated β-CD (DS = 4.9) commonly called CRYSMEB. In this previous

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• 1. A catalytic amount of copper was enough to complete the reactions. In the synthesis of trifluoromethylarenes (Ar–CF3), the cross-coupling proceeded via the pathway shown in Scheme 17 [53]. First, the fluoride-ion-induced reaction of hemiaminal 1 with CuI-diamine complex 2 gave copper alkoxide 3