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

• optimal reactivity and selectivity, each nucleophile required a slightly different chiral amine catalyst. Interestingly, vinylaniline 126f could also be added to enone 118 in moderate to good yield and with good enantioselectivity. N-Trifluoroacetyl-1,2-aminothiol (126d) reacted to give thioether products

• pathway [58]. Aromatic α-methyl enones (R1 = Me, R2 = aryl) reacted in good yield and enantioselectivity. However, when larger R1 substituents or an α-methyl enone were used in the reaction, the product was obtained with diminished enantioselectivity (58:42 to 69.5:30.5 er). After the submission of this

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• deuterium kinetic isotope effect of 2.34 was seen for C–H insertion with gold catalysis. Hashmi demonstrated the viability of dual gold catalysis for carbene/alkyne cascades with diynes like 109, which gave products from either a 1,2-methyl shift (not shown) or a C–H bond insertion to form enone 112 (Scheme

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• with catalysts C3 (94%) and C4 (96%). Under these optimized conditions a survey of imidazolones reacted with enone 29 to produce adducts with yields within the range 71–83% and with very high enantioselectivity (Scheme 5). The Michael adducts can also be transformed into different derivatives (Scheme 6

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• mixture, we decided to develop a convenient method for their preparation on a multimilligram scale. In traditional synthetic methods, the substituted pyridine ring can be constructed, e.g., by Hantzsch reaction [28][29] or by condensation of amino-enone or aminonitrile derivatives with a 1,3-dicarbonyl

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

• Melchiorre. A Diels–Alder reaction of indole-2,3-quinodimethane 76 (generated from 77 and the prolinol catalyst 78 ) with the enone 79 affords a tetrahydrocarbazole derivative 80. The NHC precatalyst 22 then promotes an intramolecular cross-benzoin condensation of the keto-aldehyde to furnish the tetracyclic

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• alkaloid raputindole A (1) from the Amazonian tree Raputia simulans. Investigated synthetic precursors B–E of the cyclopenta[f]indole moiety (A) of raputindole A (1), all to be assembled from 6-iodoindole (2). 6-Iodoindole (2) serves twice as starting material towards indole-6-yl-substituted enone 8

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• the enone unit to afford the enolate 12. Isomerization of the exocyclic olefin moiety of 12 into the endocyclic position may be assisted by internal proton transfer. Tautomerization of the resultant enol 13 to its keto form affords the final product 8aa. It may be noted that the key carbon–carbon bond

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• prepared by regioselective reduction of the carbonyl group, silylation of the resulting alcohol and further reduction of the enone moiety. An ensuing transetherification of alcohol 59 with ethyl vinyl ether gave an allyl vinyl ether, which underwent a magnesium perchlorate-promoted [1,3]-sigmatropic

• synthesize a variety of natural products containing this macrocyclic structural motif. Based on chiral enone 80 and its enantiomer, ent-80, coraxeniolide A (10) and β-caryophyllene (22) were synthesized in five and four further steps, respectively. The synthesis of 10 continued with a trityl perchlorate

• -catalyzed conjugate addition of silyl ketene acetal 81a to enone ent-80. Deprotonation and trapping of the resulting enolate with formaldehyde furnished lactone 82 in a regio- and stereoselective fashion. Introduction of the exocyclic double bond proved to be challenging and therefore salt-free, highly

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• oxidation of 8 to give the enone 1 in DMSO at high temperature (80 °C) resulted unsuccessful [24]. The hydrogenation of silyl enol ether derivatives in the presence of the IBX-N-oxide complex gives the corresponding enones, usually with better conversion and under milder conditions (room temperature) [25

• kinetic enol ether 10 in 91% yield ([α]D +19.7° (c 1.4, CHCl3)). The latter was submitted to the oxidative step with the IBX-N-oxide, but even in this case the results were unsatisfactory since only traces of enone 11 were detected. In contrast, the Pd based Saegusa–Larock methodology resulted successful

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• NMR spectra of this series showed the C=O signal at δ values within the range of 187–188 ppm, while the 1H NMR spectra showed the trans configuration of the enone moiety due to the high coupling constant of Jα,β 15.6 Hz, with the β-proton being more deshielded than the α-proton. The OCH2 signal was

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• dimerized 16-membered ring product 101 in 57% yield, which was generated by a RRM–dimerization sequence and its monomer 100 in 14% yield along with 99 in 26% yield (Scheme 20). Bicyclo[2.2.1]heptene derivatives Holtsclaw and Koreeda [25] have explored a chemoselective RRM of the enone containing norbornene

• derivative 104 were obtained in a 22:78 ratio (Scheme 21). Aubé and co-workers [26] have accomplished the asymmetric synthesis of the dendrobatid alkaloid 251F by employing a RRM as the key step. The required building block 108a has been synthesized from enone 107 via a RRM protocol. When enone 107 was

• ) reaction of ketone 109 with cyclopentadiene (111) in the presence of MacMillans catalyst 110 gave bicyclic ketone 112 in 65% yield. Then, ketone 112 was transformed into enone 107 in 80% yield by adopting the known oxidation protocol. Later, enone 107 was treated with catalyst 1 under ethylene (24

The simple production of nonsymmetric quaterpyridines through Kröhnke pyridine synthesis

• Isabelle Sasaki,
• Jean-Claude Daran and
• Gérard Commenges

Beilstein J. Org. Chem. 2015, 11, 1781–1785, doi:10.3762/bjoc.11.193

• 3 as the masked enone. Pure compound 3 was only obtained in the presence of an excess of Eschenmoser’s salt, by addition of 2 equiv of (N,N-dimethyl)methyliminium chloride to 1, in acetonitrile at room temperature. Then, compound 3 was condensed with N-[2-oxo-2-(2-pyridinyl)ethyl]pyridinium iodide

• is easily introduced on the 2,2’-bipyridine or 2,2’:6’,2”:6”-terpyridine moieties [31][32]. In fact, the use of a chiral enone (i.e., (−)-myrtenal) led to the chiral 5,6-substituted quaterpyridine 8. The corresponding platinum complex 9 was obtained by a classical synthesis, which entails the

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• had been obtained in the case of intramolecular reactions where the β-positions of the enone systems were covalently tethered. Shinohara et al. have also reported a reductive dimerization of methyl cinnamate resulting in a cis-orientation of the phenyl rings [25]. SmI2-induced reductive dimerization

• of 1,1'-dicinnamoylferrocenes had also afforded cis-phenyl-disubstituted cyclopentanols, presumably as a consequence of parallel orientation of the enone systems by fixation of the carbonyl oxygens by Sm(III) and tethering by the ferrocene unit [26]. A possible reason for our findings could be the

• capability of a deprotonated indole ring to engage into complexation with Sm(III) formed by reduction of the enone moiety (Scheme 2), leading to a gauche-type orientation of the indole moieties, as shown in structures 10 and 11. It is known that anionic indolide can form complexes with Sm(II) and Sm(III) [27

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• target molecule 1 is shown in Figure 1. RRM of the tricyclic allylated compound 2 can deliver the target lactam 1. The key synthon 2 can be derived by allylation of lactam 3, which in turn can be prepared via BR starting with the known enone 4 [25][26][27], derived from dicyclopentadiene (5) [28][29][30

• ]. Results and Discussion To begin with, the oxidation of dicyclopentadiene (5) in the presence of SeO2 gave 1α-dicyclopentadienol (6), which on treatment with pyridinium chlorochromate (PCC) [31] delivered the known tricyclic enone 4. Selective reduction of enone 4 with Zn in AcOH/EtOH under reflux

• and hoped for a different outcome during the BR. In this content, oximation of the enone 4 was carried out with NH2OH·HCl in the presence of NaOAc in dry MeOH. The stereoisomeric oximes, i.e., (E)-11b and (Z)-11a were separated by silica gel column chromatography to deliver 47% and 23% yields

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

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

• examined. In the course of these studies, numerous scaffolds were synthesized, including a furan, a cyclopentenone, an acyclic enone and even a naphthalenone. The diversity of these structural motifs lies in novel cascades of reactions originating from a common carbocationic manifold. Keywords

• cyclopentanone but promoted the formation of furan 18 (54% yield, entry 4, Table 1). Interestingly, substitution of the carbinol part by an n-butyl substituent provided an alternate type of product: the acyclic enone was the sole product isolated from the reaction medium (47% yield, entry 5, Table 1). It could

• article, we demonstrate the delicate balance among several mechanistic pathways by a minor change of substrate in acid-catalyzed rearrangements of 1-styrylpropargyl alcohols. Indeed, these compounds may generate a furan (18), an enone (19), an allylic ether or even a naphthalenone (17). The formation of

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• formation of a complex with boric oxide, followed by reaction with vanillin. Instead of boric oxide, alkyl borates and boric acid can also be used. The first attempt at modification was to truncate the general structure to either a single enone or dienone system. The latter structure contained a

• superior inhibition to that of the natural parent product. This work was followed by more comprehensive bioactive studies on aromatic enones utilizing the substituted chalcone backbone [26]. The study showed that the presence of the enone moiety played an important role in maintaining the activity in the

• curcumin analogs. Using this principle, Ahn et al. (2005) [27] left the enone unchanged and prepared various curcumin mimics with asymmetric units bearing alkyl amide, chloro-substituted benzamide, or heteroaromatic amide moieties. These analogs exhibited a stronger anti-angiogenic activity against HUVECs

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

• allylzinc reagent and no reaction was observed. When the allylzinc reagent was premixed (1:1) with MeCN before adding to 5a, 6aj was not observed. Instead, enone 8a was observed as the sole product. Conversely, when the allylzinc reagent was added to 5a, suspended in anhydrous THF, 8a was not observed. The

• electrophilic aromatic substitution at the 2-position of the N-aryl moiety. (The isolation of enone 8a and the fact that 5a does not react with oct-1-ene under the same conditions rules out a Diels–Alder-type pathway to 8b.) Formation of side-products 7a and 7b can be rationalised by dimerisation of allylzinc

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

• , the acryl system shows differences in reactivity upon slight structural modifications. In such a system, the enone and acrylonitrile are more reactive, while with the acrylate reaction is relatively slow. Furthermore, there is a decrease of reactivity with acrylamide due to the reduced Michael

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• enone fragment. HMBC correlations from H2-8 to C-7 and C-12 secured the connectivity of the C-8 to C-7. The connectivity of C-6 to the ketone carbon C-13 through an ester linkage, which was also supported by the downfield chemical shift of C-6 (δC 88.6) completed the structure of 6/5/6 tricyclic

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

• was crossed with methyl vinyl ketone in 62% yield [34]. Reduction of enone 34 was achieved in the presence of Pd/C with H2 in EtOAc to furnish diketone 35 [34]. Chemoselective Wittig mono-olefination of 35 provided ω-enone (−)-32, spectroscopically identical to the material in Danishefsky’s racemic

• enantioselective synthesis of the (4aS,8aR,8S)-hydrolilolidone core 37 [63][64] present in aspidospermine (36), and thus a formal total synthesis of the alkaloid itself, intercepting Stork’s classic route [61]. One precursor described in the core synthesis is enone 38, which bears the quaternary stereocenter of

• of installing the γ-stereocenter of the target 38 was addressed as follows: LiAlH4 treatment of (+)-43 gave exclusive 1,2-reduction. When the crude product was hydrolyzed, β-elimination gave the desired enone 38. The overall formal synthesis represents a rare example of enantioselective Stork

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

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

• enolization. Thus, treatment of Δ5-cholestenone with 24a yielded the unconjugated olefin 27a in addition to recovered unreacted enone, whereas phosphorus ylides would form Δ4-cholestenone via enolization and double bond conjugation [20]. Other monocyclic phosphonamides with application in olefination

• palladium catalysis and subsequent decarboxylation yielded enone 118 as a single diastereomer. Addition of the Li anion of phosphonamide 24c to enone 118 afforded adduct 119 as a single isomer, with the attack occurring to the less hindered face of the enone. Further elaboration of the side chain was

• chiral auxiliary through ozonolysis followed by protection of the side chain as TBDPS ether afforded cyclopentanone 155. Saegusa–Ito oxidation followed by epoxidation of the formed enone gave 156 as the major isomer (dr 9:1). Regioselective reductive opening of the epoxide with Na[PhSeB(OEt)3] produced

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• , a precooking treatment to manually deactivate 1 was desired. We hypothesized that the modification of the reactive enone functionality or the degradation of the cyclic structure may eliminate the bioactivity of 1, and envisioned that the treatment with an alkaline solution may serve this purpose. In

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• as presented in Scheme 2. Cyclohept-4-enone (49) has recently been reported from several actinomycetes [2]. Some terpenes could be identified as well. 2-Methylisoborneol (60) and geosmin (62) are commonly produced by Streptomyces and other actinomycetes [3][30]. In addition, the sesquiterpene