Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• not suitable for some acid-sensitive or base-sensitive intermediates. Alternatively, the lactone is also formed through the reaction of a carbonyl with an enolate that can be generated from a metal-catalyzed conjugate addition of an α,β-unsaturated diester. As shown in Figure 1, it involves a

• condensation [20]. Therefore, it is rationalized that an α,β-unsaturated monoester-derived enolate should react preferentially with the keto group in the keto ester to yield the alkoxide, which further lactonizes with an intramolecular ester group to form the lactone. It should provide a novel three-step

• -lactone with a γ-exo-ester group, in 90% yield (Table 1, entry 1). Since the existing methyl methacrylate may also compete as the enolate acceptor, the high yield of 3aa indicate that lactonization of the aldolization alkoxide B proceeded much faster than metathesis of B with a silane, which gave γ

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• in the solution, and consequently the C–S bond cleavage seems to take place more favorably than a deprotonation. A similar effect on the suppression of defluorination of CF3-enolate anion in the presence of a large amount of fluoride ions has been reported [38]. On the other hand, it is known that

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• catalysts are used in combination with various stoichiometric oxidants including oxygen [16][21]. However, nucleophilic trappings of resultant iminium salts are typically exemplified with highly stabilised carbon nucleophiles such as cyanides, nitronates, enolate equivalents and heterocycles (Scheme 1) [14

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• positive. In order to find the best conditions, several reactions were carried out. Increasing the reaction time to 5 days resulted in 56% yield (Table 1, entry 2). An increase in the loading of acrylamide (2 equiv, in order to generate more enolate) was helpful and resulted in 71% yield (Table 1, entry 3

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• with alkyl halides virtually yield single stereoisomers, in which the configuration of the newly formed stereogenic center at C-2 of the amino acid moiety is the same as that in the proline moiety of the chiral auxiliary in the starting material. In reactions of the enolate of this chiral glycine

• acetophenone in only four steps in an overall yield of 30%. A similar protocol for the synthesis of 3-alkylphenylalanines was independently developed by Soloshonok et al. [56]. These authors used sodium hydroxide for the deprotonation of 10 and 1-phenylalkyl bromides for the alkylation of the enolate. Once

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

• decayed at or above +3 °C through proton transfer from the solvent that was cleaved into ethylene and the enolate LiO–CH=CH2 [the latter identified through δH = 6.93 ppm (dd) and confirmed by δC = 81.9 and 158.9 ppm]. In t-BuOMe as the solvent, a purified sample of [6Li]4&TMEDA (entry 5, Table 1

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• construction of building blocks bearing quaternary carbon and fully substituted tertiary centers [1][2]. A recent addition developed by our laboratory is the allylic alkylation of nonstabilized enolate precursors to form α-quaternary carbonyl compounds (Scheme 1) [3]. Once the key stereocenter is set by this

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• ethyl acetate to afford the adduct 19. Diastereoselective methylation of the ester enolate moiety of 19 with MeI afforded only the anti-product 20 [32][33], which was then subjected to the deprotection of the TBDPS group with HF·pyridine, followed by cleavage of the ethyl ester group in 21 to give the

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• summarized splendidly in several reviews, we do not cover these transformations, except for selected examples related to other reactions. Review 1 Chiral phosphine catalysts Nucleophilic phosphine catalysis often involves the formation of Lewis adducts, namely phosphonium (di)enolate zwitterions, as reaction

• -RC reaction between the α,β-unsaturated imine and the enolate, followed by an SN2 reaction. 2.14 Annulations through double-Michael additions The bisphosphine-catalyzed double-Michael addition of dinucleophiles to electron-deficient alkynes provides an efficient approach for the synthesis of

• bond between the amide NH proton and the enolate oxygen atom assisted the Michael addition from the si-face of the enolate. The alternative re-face attack was blocked by the 3,5-bistrifluoromethylphenyl group (Scheme 55). 2.17 γ-Umpolung additions of allenes or alkynes In the phosphine-catalyzed

Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2014, 10, 2021–2026, doi:10.3762/bjoc.10.210

• the formation of 12 and 15 in the aldol reaction, both containing endo-configurated OH groups only (Scheme 4). The reaction is initiated by proton abstraction from one of the acetyl groups (9→16). The resulting enolate subsequently attacks the vicinal acetyl group, pushing the developing alcoholate

• mechanism is followed during the formation of the main product 15, the only difference between the pathways being the enolate formation, i.e., whether the second five-membered ring is produced by deprotonating a syn- or anti-positioned acetyl group. To learn more about the chemical properties of the above

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• used for limited exploratory studies. Cyclopropanation and aziridination The cyclopropanation of α,β-unsaturated esters and lactones using chiral phosphonamide reagents is a special case of the conjugate addition–enolate alkylation sequence. The application of chloroallyl phosphonamides such as (trans

• ,R,R)-47a in the conjugate addition to enones provides the corresponding fused endo,endo-cyclopropane 50a in high diastereomeric excess [51]. The transformation proceeds via the intermediate Michael adduct 49, which eliminates chloride after stereocontrolled attack of the enolate to afford

• methyl iodide afforded adduct 177 with excellent selectivity (dr > 95:5) (Scheme 22). Ozonolysis with reductive work-up and ensuing protection of the formed hydroxy group as TPDPS ether provided lactone 178. Addition of the enolate of tert-butyl acetate to 178 and ketal formation afforded 179. Reduction

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• synthesis from imines is similar to that reported for activated alkenes [40]. This tandem protocol has two steps, the first being a Mannich addition of the enolate to the imine. To find out whether Mannich addition is palladium catalyzed, we carried out two reactions of tosylimine 1a with methyl

• propose a plausible mechanism for 3(2H)-furanone synthesis from tosylimines and 4-chloroacetoacetate (Scheme 3). The reaction starts with the Mannich addition of the enolate 15 to the carbon atom of the imine double bond to form intermediate 16. This step is the same for both the catalyzed and the

• closure towards the formation of 3(2H)-furanone is initiated by the abstraction of the acidic proton by the base and consequent ester enolate attack to the end carbon of the oxy-π-allylpalladium intermediate. Having established an efficient method for the synthesis of highly functionalized furanones from

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• 5. The alkylation step was optimized and it can be conducted with an enolate concentration of 4 up to 0.25 M in dioxane (Table 1). The attempt with higher enolate concentration was not smooth due to the increased viscosity of the reaction mixture and thus low efficiency of stirring, even with a

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• prepared using electrophilic fluorination of enolate esters [64][65][66], deoxofluorination [67][68][69] nucleophilic [70] and electrochemical fluorination [71][72] strategies. Attempts to prepare 2-fluoro-2-(2,4-dinitrophenyl)acetic acid by an analogous process led to the isolation of a benzyl fluoride

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• reagent and solvent. Finally, enolate is another nucleophilic species that was engaged in the AT reaction as shown in Scheme 18. In this reaction, an allenylketone was mixed with NaH in THF at −10 °C. After deprotonation (30 min), diethyl phosphite in CCl4 was added dropwise. Treatment with acetic acid

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• appears as a common procedure, affording chiral tertiary alcohols which are ubiquitous in the biological sciences and pharmaceutical industry [1][2][3][4][5][6]. The decarboxylative aldol reaction, broadly used for the generation of ester enolate equivalents by the promotion of releasing CO2, has become

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• on the corresponding reaction of fullerenes, the mechanism in Scheme 6 is proposed for the Bingel–Hirsch reaction of circumtrindene. The enolate generated by deprotonation of bromomalonate 18 with DBU functions as a nucleophile; it attacks one of the strongly pyramidalized carbon atoms of

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• reacted with an (E)-boron enolate formed by the reaction of thiophenol propionate with chlorodicyclohexylborane and dimethylethylamine, similar to the conditions described by Paterson et al. for lactate-derived auxiliaries [18]. In this way, the aldol product was conveniently obtained as an inseparable 1

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• directly (as in the case of Fischer’s base (7)) or generated in situ by deprotonation of the benzothiazolium salt 9. Hence, in both cases a resonance-stabilized iminium–allenyl enolate 13 is formed. Here, the bifurcation of the sequences takes over. Based upon product analysis the pathway to the formation

• by very similar levels of diastereoselectivity of the double-bond formation. In contrast the formation of the merocyanines 10 starts with a proton transfer from the CH-acidic α-position of the iminium moiety of 13 to the amide enolate part. The resulting enol 15 is part of an allenyl enol, which is

• minute electronic distributions in the zwitterionic key intermediate, which is controlled in the allenyl enolate moiety by the indolyl nitrogen substituent R1 and by the fragment X on the iminium part, which participates in the stabilization on that side of the zwitterion. The former hypothesis is

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• coupling (Scheme 3). Allyl- and enolsilanes serve as important substrates in numerous synthetically useful ground and excited state reactions [53][54]. The most common roles of these substances are to act as the respective equivalents of allylic anions and enolate ions. When coupled with strong

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• Scheme 21). This can be a simple nucleophile (indole 30, imidazole 31, diethyl phosphite (32), Scheme 20) [53][54][55] or can be generated in situ (enolate 33, enamine 34, Scheme 21) [56][57] from a suitable precursor and a second catalyst (dual activation strategy) affording 1,3-disubstituted-1,2

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• multigram quantities within five steps from Cbz-valine (8), adapting a convenient sequence developed for dolaisoleuine by Pettit and co-workers [5]. Cbz-protected N-methylvalinol (4) [6] was oxidized to the aldehyde 5 under Parikh–Doering conditions, followed by aldol addition of the lithium enolate of t

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• the thermodynamic enolate of 2-methylcyclohexanone (5) and the bicyclic electrophile 12 (Scheme 2). A challenging synthetic problem appears to be the construction of the stereochemically dense trans-fused C–D ring system 12, which possesses four stereogenic centers including two contiguous asymmetric

• (−)-quinic acid (16) according to the route reported by Arthurs et al. [40] with minor modifications. After Baylis–Hillman reaction and subsequent silylation of the resulting free primary hydroxy group, substrate-controlled α-methylation of the lithium enolate proceeded with full stereocontrol [41][42

• tosylation of the primary alcohols in 19, 20 and 22 gave suitable electrophiles for the planned O-alkylation with the thermodynamic enolate of 2-methylcyclohexanone. However, under various conditions (NaH/15-crown-5/THF; t-BuOK/18-crown-6/THF/DMPU; KHMDS/THF) [44][45], the intended O-alkylation to yield the

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

• -catalyzed cyclopropanation of silyl-enol-diazo compound 101 and Boc-protected pyrrole 147 resulted in the formation of intermediate cis-divinylcyclopropane 148, that rearranged under the reaction conditions to give the corresponding highly substituted bridged cycloheptadiene 149. Deprotection of the enolate

• acid was converted to the corresponding anhydride, which could be reduced to the alcohol using NaBH4, followed by reoxidation with DMP to yield aldehyde 154. Attachment of furanone enolate 155 [134][135], followed by reoxidation yielded tricycle 156. Deprotection of the amine and the MOM-protected

• TMSCN [159][160][161], followed by protonation of the TMS-enolate and esterification of the intermediate acyl cyanide yielding allyl ester 191. This ester was transferred into the corresponding carboxylic acid, followed by formation of the acid chloride. The chloride was displaced with an azide, which

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• aldehydes also gave the morpholinium 2-pyrrolidinon-3-olates 2b–2e (Table 2, entries 2–5) in 65–87% yields, respectively. The formation of morpholinium 2-pyrrolidinon-3-olates 2a–2e clearly indicated that the reaction initially gave the expected 3-hydroxy-2-pyrrolidinone, which in turn converted to enolate