Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• occur on the oxygen atom which is doubly bonded to the phosphorus atom. This protonation likely yields the intermediate I (Figure 8) which exists as two mesomeric forms. Then, two competitive mechanisms can occur. Intermediate I can lose a carbocation according to a SN1 mechanism whereas the second way

• could consist in a nucleophilic substitution (SN2) involving chloride ions as nucleophilic species to produce the intermediate II. Then, a repetition of this mechanism yields phosphonic acid. The preponderant route is likely governed by the stability of the carbocation and the steric hindrance around

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• process to stabilize the carbocation species. This method was proved to be efficient by performing the reaction at 9.7 mmol scale to obtain 84% yield of the product. C–O bond formation reaction Carbon–oxygen (C–O) bonds are widely present in molecules containing ester, carbamate and amino acid, etc. [88

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• hydrogen is then transferred to TEMPO resulting in a radical–TEMPO–Cu intermediate Z. The benzyl radical in Z is then further oxidized to the corresponding carbocation which gets deprotonated to afford dihydroquinazoline Z´ along with Y´ and TEMPOH. Finally, Z´ is further oxidized to 73. TEMPOH oxidizes

Correction: Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2017, 13, 1669–1669, doi:10.3762/bjoc.13.161

• Stephanie R. Hare Dean J. Tantillo Department of Chemistry, University of California–Davis, 1 Shields Avenue, Davis, CA 95616, USA 10.3762/bjoc.13.161 Keywords: carbocation; density functional theory; dynamics; mechanism; terpene; The originally published Figure 6 had several mis-drawn

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• oxonium ion 7 evolves to isochromanone 4c, while the 4-methoxybenzyl carbocation is sufficiently long lived to react with acetonitrile and afford acetamide 5 upon reaction with traces of water. Interestingly enough, when the reaction was performed in acetone, compound 4c was isolated in lower yield (60

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• carbocation, prolonged heating of the oily residue was avoided. Precipitation from MeOH quantitatively removed the traces of the DMTr carbocation as a methyl ether. Couplings were carried out in a 1:1 (v/v) mixture of DMF and MeCN using standard phosphoramidite building blocks (1.5 equiv) and 4,5

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• vinylic carbocation undergoes an electrophilic attack at the neighbouring alkyne, which in turn reacts with the sulfonamide oxygen nearby. Both steps are strongly facilitated by the geometry changes when the linear alkyne moieties convert into bent alkene ones, as the reactive centre is literally pushed

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• of the substrate coordinating cavity. Recently reported targeted engineering [51] of the Class I taxadiene synthase from Taxus brevifolia (TXS) enabled new understanding of the mechanistic procedures that are carried out by this enzyme on the substrate GGPP. Quenching the carbocation cascade that

• labda-13-en-8-yl diphosphate carbocation intermediate and the formation of halima-5(10),13-dienyl diphosphate (Scheme 2). In wild-type Class II diterpene synthases, the labda-13-en-8-yl diphosphate carbocation undergoes either single deprotonation or a cascade of hydride and methyl group shifts prior to

• deprotonation with occasional hydration at the C8 position of the carbocation intermediate which yields hydroxylated diphosphate products [62]. MvCPS1, however, catalyzes a C9–C8 hydride shift preceding hydration resulting in the labdane-type diterpene precursor for the antidiabetic marrubiin [63]. Double

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• loss of AcOH leading to compound (+/−)-15 with 85% yield. The 1,3-allylic transposition of the hindered tertiary alcohol group under acidic conditions has not been reported yet for such compounds. It may conceivably that such a transposition occurs through the formation of an allylic carbocation which

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• (NIS) in nitromethane. The resultant carbocation-like species presumably underwent a 1,2-alkyl shift to provide a silylated oxocarbenium ion. The following silyl cation trapping with a bromide anion resulted in 2-phenylcycloheptanone. When a chiral substrate (59% ee) was treated with NIS, a product

• with significantly lower ee (11%) was observed. These results suggest that the reaction might proceed mainly in a stepwise SN1-like manner, via a benzylic carbocation intermediate. Despite the fact that several variants of chiral halogen bond-donor catalysts have been synthesized, to the best of our

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• group of 5 and/or 9, leading to the formation of a stable 3°carbocation that can undergo further dehydration reactions until full aromatization to the naphthalene ring is achieved. This study would serve to help us to find the real scenario. Finally, in the presence of Lewis/Brønsted acids, substrates 6

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• rate on the stability of the intermediate carbocation is even more evident in the series of primary benzylic alcohols. Among them only the p-methoxy-substituted compound 1c shows high activity. In particular, with thiol 2e some ether was formed that during time is converted into the product (Table 2

• , entry 15 and Figure 5). On the other hand highly hindered alcohol 1g with a tertiary carbinol atom gave a very fast and selective reaction (Table 2, entry 11). Thus we can conclude that the reaction rate follows the carbocation stability according to an SN1 mechanism. To confirm this hypothesis the

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

• previous analogous reactions, a relatively stable carbocation intermediate was more likely to have formed in this aminochlorination reaction (Scheme 6). Moreover, when the carbocation intermediate was formed, strong electron-withdrawing groups at the phenyl ring in the 3-position of the carbocation are

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• hydrophobic cavity from which water is excluded to enable carbocation chemistry in an aqueous environment. Furthermore, the hydrophobic cavity provides a template that arranges the substrate in a certain conformation to determine the formation of a specific product. Single residues such as phenylalanines are

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

• improved orbital overlap. Protonation of the hydroxy group of 9 under the reaction conditions likely leads to the corresponding tertiary carbocation under equilibrium. The nitrogen lone pair can then assist the electrophilic cyclisation reaction, augmented by improved orbital overlap with the aromatic π

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

• feature of the Criegee rearrangement is that the Criegee intermediate rearranges into a carbocation. The mechanism of the Criegee reaction is presented in Scheme 38. Initially the reaction of the peracid with the tertiary alcohol 122 produces perester (Criegee intermediate) 123. One alkyl substituent

• migrates from the carbon atom to the adjacent oxygen atom and replaces the carboxylic acid moiety to form carbocation 124. Then, the addition of water to carbocation 124 affords ketone 125 and alcohol 126. p-Nitroperbenzoic acid is usually used to oxidize tertiary alcohols because the anion of this acid is

• the peroxide oxygen atom and the elimination of a water molecule to form carbocation 169. The carbocation 169 is attacked by a water molecule, a proton is transferred to the oxygen atom attached to the phenyl group, and finally the cleavage of the adduct yields phenol (170) and acetone (171). The Hock

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• been proposed in Scheme 6, the reaction can adopt a SET mechanism leading to the intermediate 23a, after C-alkylation. Compound 23a in turn gets converted into intermediate aryl radical 23b. From this intermediate another intermediate aryl carbocation 23c is formed by transferring a single electron to

• the oxidant. Carbocation 23c is stabilized by the amide nitrogen as shown in 23d. Eventually, in the presence of base, rearomatization of 23d takes place to afford the final product of the oxidative coupling reaction. Kündig et al. in their oxidative coupling process using 2.2 equivalent of CuCl2

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• tertiary carbocation is trapped by a gold carbenoid intermediate to form the fused cyclopropane. While there had been reports of utilizing chiral ruthenium complexes for asymmetric catalysis prior to our studies [30][31][32][33][34][35][36][37][38][39][40], there had previously been no reported examples of

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• . The formation of such species from simpler non C=C containing starting materials has been reported and established (1H NMR) by Gopius et al. [52]. Accounting for the exclusive formation of O-acetate rac-83 the trapping of the more stable 2° allyl carbocation intermediate 82 (generated via ring-opening

• of rac-81) with nitrate is preferable to the formation of the higher energy/more unstable 1° carbocation 80 (generated via ring-opening of rac-79, Scheme 13). Subsequent formation of rac-83 allows its hydrolysis with potassium carbonate in methanol to generate the observed rac-16. Isoprene and

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

• their characteristics of convertion to vinyliminium species or the delocalized carbocation intermediates in the presence of Lewis or Brønsted acids (LA or BA). In addition to the aforementioned studies on the nucleophilic substitutions, another research focus is the 3-indolylmethanol-based cycloaddition

Recent advances in C(sp³)–H bond functionalization via metal–carbene insertions

• Bo Wang,
• Di Qiu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2016, 12, 796–804, doi:10.3762/bjoc.12.78

• computational study of the likely intermediate suggests that it is best described as a zinc-bound carbocation rather than a zinc carbene (Scheme 12). Notably, Zn is a cheap, earth-abundant 3d metal, thus making it attractive as catalyst for C–H bond functionalization. Conclusion The intermolecular metal–carbene

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• transformations. Cautions for analyzing both experimental and theoretical data on carbocation rearrangements are included throughout. Keywords: carbocation; density functional theory; dynamics; mechanism; terpene; Review Introduction to terpene forming carbocation rearrangements Terpene natural products display

• rings that are transformed in only one or two enzyme-promoted reactions. These reactions involve generation of a carbocation by protonation or loss of a diphosphate group followed by cyclization, alkyl shift, hydride shift and/or proton transfer reactions to generate new, more complex, carbocations

• . Ultimately these carbocations are either trapped by a nucleophile (e.g., water, diphosphate) or deprotonated to form alkenes. The details of terpene-forming carbocation cyclization/rearrangement processes have been of interest for decades [1][2][3][4][5][6]. Although much has been learned, new observations

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• spirocyclization of the alkoxy radical D onto the benzene ring affords cyclohexadienyl radical F, oxygenation of which followed by C=O bond formation finally provides the oxaspirocyclohexadienone product 3a. Whereas, the oxidation of the benzylic radical B by the existing Cu(II) species to carbocation G and

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• formation of the stabilized carbocation 11 that may evolve through two pathways. This intermediate may either undergo a ring closure due to the nucleophilic character of the silylated alkyne (pathway A) or react with an oxygenated nucleophile, such as the perrhenate anion, to generate the transient

• isolated. This observation strengthened the hypothesis that the silyl group stabilizes the carbocation intermediate which seems necessary for the cyclization step. Conclusion The discovery of new reaction manifolds often provides a good opportunity to discover novel reactivity in related systems. In this

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• to the carbon atom to generate the most stable carbocation. The most stable carbocation is the benzylic carbocation which would not undergo a rearrangement. As discussed above, when the cyclization reaction of 15 was carried out with [(NHC)AuCl] complexes (Table 1, entry 5), the starting material was