Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• structures as esters of silibinin (major product, 8a, 8b) and hydnocarpin D (minor product, 9a, 9b). 2,3-Olefination was further proven by hydrolysis of compound 9a, which converted the esters into the racemic mixture of (10R,11R)- and (10S,11S)-hydnocarpin D (enantiomers 2a and 2b). We then systematically

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• [18][19], decarboxylative alkenylation of cycloalkanes with aryl vinylic carboxylic acids [20][21], trifluoromethylthiolation [22], thiolation [23][24], alkenylation [25][26], dehydrogenation−olefination and esterification [27][28], radical addition/1,2-aryl migration [29], cascade alkylation

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• TFA/H2O (9:1), 100 °C, 24 h. Synthesis of benzaldehyde derivatives 14 and 15: i. Pd(PPh3)4, Bu3SnH, THF, CO (1 atm), 50 °C, 2–3 h, 70%. Olefination reactions of 15 and the X-ray structure of 17 (CCDC number 1432194): i. Zn, TiCl4, THF, 0 °C to reflux, 12 h; ii. Pd/C, H2, EtOAc, 20 °C, 16 h, 76% over 2

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

• to sodium tert-butoxide gave rise to the epimerized trans-isomer 48. Finally, the exocyclic double bond was introduced by olefination of ketone 48 and thus completed the racemic total synthesis of β-caryophyllene (22) in 13 steps. This elegant synthesis received considerable attention and revealed

• . Reductive desulfonylation and a final Wittig olefination of the ketone then afforded racemic β-caryophyllene (22). In summary, the total synthesis of β-caryophyllene was achieved in 19 steps with an overall yield of 6.3%. Although the key intramolecular acyl transfer reaction for construction of the

• product 63 in very good yield, however, as a mixture of lactol epimers (α/β ≈ 56:44). Silyl protection of the lactol and subsequent Tebbe olefination [42] of the ketone group installed the exocyclic double bond of the nine-membered carbocycle. Desilylation followed by oxidation with silver carbonate then

A new approach to ferrocene derived alkenes via copper-catalyzed olefination

• Vasily M. Muzalevskiy,
• Aleksei V. Shastin,
• Alexandra D. Demidovich,
• Namiq G. Shikhaliev,
• Abel M. Magerramov,
• Victor N. Khrustalev,
• Rustem D. Rakhimov,
• Sergey Z. Vatsadze and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2015, 11, 2072–2078, doi:10.3762/bjoc.11.223

• , 28 Vavilov Street, Moscow 119991, Russia 10.3762/bjoc.11.223 Abstract A new approach to ferrocenyl haloalkenes and bis-alkenes was elaborated. The key procedure involves copper catalyzed olefination of N-unsubstituted hydrazones, obtained from ferrocene-containing carbonyl compounds and hydrazine

• of vinyl groups: while for the monoalkene containing molecules no reduction is seen, the divinyl products are reduced in several steps. Keywords: catalytic olefination; copper catalysis; cyclic voltammetry; ferrocene; Introduction The introduction of complex functional fragments into the specified

• –Fuchs reaction) using a 2–4-fold molar excess of triphenylphosphine [27][28][29][30][31]. Results and Discussion Synthesis of halovinylferrocenes A few years ago we discovered a new reaction for a double carbon–carbon bond formation – the reaction of catalytic olefination. It was shown that the copper

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

• synthetized through direct olefination [44]. In 2012, Zhang and co-workers reported one example of the use of 3-bromo-1,2,4,5-tetrafluorobenzene with iodoanisole as coupling partner (Figure 1c) [45]. The reaction conditions tolerate the C–Br bond on the polyfluorobenzene allowing the synthesis of (hetero)aryl

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

• the fruiting body of P. igniarius, is a well-known anticancer agent. To assemble the spiro-fused furanone core of phelligridin G, Wright and Cooper [55] have used a RRM process as a key step. Wittig olefination of furylbenzaldehyde derivative 265 using methyltriphenylphosphonium bromide in the

• presence of n-BuLi provided styrylfuran 270 in 72% yield. The DA reaction of styrene derivative 270 with DMAD 129 at 40 °C yielded oxabridged compound 268. Another route to 268 involves a DA reaction of 265 with DMAD at 55 °C for longer reaction time (3 days) and sequential Wittig olefination. The spiro

• olefination to result the required oxabicyclo[3.2.1]octene derivative 338. Later, the RRM of the styrene derivative 338 with catalyst 2 delivered a highly-functionalized spiro-pyran derivative 339 in 48% yield (Scheme 74). The Dysiherbaine and acetogenin groups of natural products have been synthesized by the

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• . Although fragment syntheses vary, the late-stage fragment assembly of the dactylolide macrocycle has centred mostly around construction of the C1–C5 dienoate by Wittig-type olefination reactions followed by ester hydrolysis and esterification with the C19 hydroxy group, combined with metathesis to form 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

• -selectivity we attempted to adapt Schlosser's procedure for the olefination of aldehydes to the chloromethylenation of ketone 24 [38]. Selectivity towards the E-isomer was rather poor with an E/Z-ratio of 1.6:1 (Scheme 5). Separation of indiacen B (2) and its Z-isomer 26 was possible by semipreparative normal

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

• solution gave the cycloalkene 222 which on subsequent hydrogenation yielded the targeted normuscopyridine (223, 68%, Scheme 36). Donohoe and coworkers [172] have reported the synthesis of muscopyridine (73) by RCM as a key step. The Wadsworth–Emmons olefination of the commercially available undecenal 224

Carboxylated dithiafulvenes and tetrathiafulvalene vinylogues: synthesis, electronic properties, and complexation with zinc ions

• Yunfei Wang and
• Yuming Zhao

Beilstein J. Org. Chem. 2015, 11, 957–965, doi:10.3762/bjoc.11.107

• ]. This olefination reaction went completion within 3 hours to give DTF 4 in 77% yield after column separation. Compound 4 was then subjected to an oxidative dimerization in CH2Cl2 at room temperature using iodine as oxidant. The dimerization gave TTFV 5 as a stable yellow solid in 80% yield

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• lead to improvements in the synthesis of 9, but rather made the sequence of Wittig–Horner olefination and asymmetric hydrogenation slightly less efficient. In contrast to uridine derivatives [48], thymidine analogues are significantly more robust towards unwanted reduction of the 5,6-double bond in

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

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

• olefination In 2009, Tang and Zhou developed an annulation through tandem Michael addition/Wittig olefination, mediated by the chiral phosphine BIPHEP, for the synthesis of optically active cyclohexa-1,3-diene derivatives (Scheme 54) [97]. Although this reaction required a stoichiometric amount of chiral

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• preparation of substrates 20–23 having a symmetrically disubstituted C–C double bond is depicted in Scheme 2. The synthesis started from known threose 15 [31] followed by a common synthetic sequence comprising the olefination reaction and the hydrolysis of the acetonide protecting group. Thus, Horner

• –Wadsworth–Emmons olefination of aldehyde 15 furnished the corresponding separable mixture of Z and E alkenes 16 and 17. In the case of utilising stabilised phosphorane ylides, the Wittig reaction provided only Z alkenes 18 and 19. Following acidic hydrolysis provided α-O-benzyl substrates 20–23 in good

• olefination using (methylidene)triphenylphosphorane ylide and final hydrolysis of the acetonide provided the desired C5-substrate 30. The synthesis of substrates 24–28 bearing an allylic hydroxy group is pictured in Scheme 3. At first, the ester group of previously prepared intermediate E-17 was reduced using

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

• summarized, as well as an overview of the synthesis of the employed phosphonamide reagents. Keywords: conjugate addition; cyclopropanation; olefination; organophosphorus; phosphonamide; total synthesis; Introduction Chiral non-racemic and achiral cyclic phosphonamide reagents 1–7 (Figure 1) have been

• ][14]. These methodologies will be mentioned where appropriate but not discussed in detail. Olefination Monocyclic phosphonamide reagents of type 1 bearing a N,N’-dialkylethane-1,2-diamine backbone were first reported as olefination reagents by Corey and Cane [15] and later by Savignac [16][17], and

• 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

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• synthetic feasibility of approach b), namely the cyclopropanation of the corresponding terminal olefin derivative 18. To explore this alternative approach, we managed to prepare the ethylidene derivative 18 by using either the Wittig or the Tebbe olefination reaction [34][35][36][37]. The former reaction

• byproduct 19 was isolated from the reaction mixture. To overcome this synthetic hurdle and to obtain amounts of the key intermediate 18 which are large enough to investigate its reactivity in the following cyclopropanation reaction, we decided to attempt the Petasis olefination reaction [38][39]. The

• ratio: 49%, 33%), the others minor (12%, 3%, 1.8% and 1.2%, respectively). The presence of two unexpected additional diastereoisomers can be explained based upon a partial racemisation of the chiral center next to the nitrogen, most likely occurring during the Petasis olefination reaction of

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• mechanistic pathways. Our experiments (Scheme 6) afforded quantum yields of Φ > 1 for the heterobiaryl coupling [15] and the Heck-type olefination with styrene [16], respectively. This indicates that in addition to a photocatalytic path (Scheme 2, A) radical-chain propagation is operating under the reaction

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

• substituents have been constructed [20]. Starting from 3, the first conjugate addition using (R,SFe)-L1 afforded 4, as expected in high yield and excellent enantiomeric excess (Scheme 1). Reduction with DIBALH, followed by Horner–Wadsworth–Emmons olefination and again asymmetric conjugate addition gave 6 in 77

• Markiewicz, comprising a vinylogous Horner–Wadsworth–Emmons olefination, offered in principle a very efficient procedure to obtain dienoate 13 (Scheme 3), and would leave only a single step in the synthesis of 2 [25]. Therefore, reagent 12 was prepared in two steps. After quantitative conversion of 10 into

• the reduction of 13 with DIBALH is a clean reaction, affording essentially pure 2 after work-up, the preparation of pure 13 was highly desirable. A stepwise olefination approach was therefore considered. Wittig reaction of aldehyde 11 with phosphorane 14 to give 15 was carried out first (Scheme 4) [27

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• ]. While targeting the synthesis of 2a, the Wittig olefination of 3a with n-hexyltriphenylphosphonium bromide and t-BuOK gave olefin 4a as a diasteromeric mixture of Z and E-isomers in the ratio 9.5:0.5 as shown by 1H NMR of the crude product. The catalytic hydrogenation of alkene 4a with 10% Pd/C in

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

• allylation as well as an anti-selective aldol reaction. Reference compounds representing the E- and Z-configured double bond isomers as potential products of the dehydratase reaction were obtained from a common precursor aldehyde by Wittig olefination and Still–Gennari olefination. The final deprotection of

• should be accessible from aldehyde 11 through a Horner–Wadsworth–Emmons reaction and the Still–Gennari olefination as well as by a Wittig olefination with stabilised phosphoranes, respectively. The aldehyde 11 should be accessible from the known molecule 13 via 12 [15]. Synthesis of the common precursor

• target SNAc thioester 6a in a total yield of 12% over 14 steps. Alternative attempts to synthesize 9a and 9b by Horner–Wadsworth–Emmons olefination and Still–Gennari olefination with the respective phosphonates gave no reaction product at all (Horner–Wadsworth–Emmons olefination) or only the (E,E)-diene

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods. Results: The combination of (chlorodifluoromethyl

• of aldehydes by using ClCF2CO2Na/PPh3 [19]. In 1967, Burton and Herkes suggested that the ylide intermediate involved in the olefination process was more likely to be formed by the decarboxylation of a difluorinated phosphonium salt rather than the combination of :CF2 and a phosphine (Scheme 1

• , reaction 1) [20]. Their suggestion is based on the accelerating effect of PPh3 on the thermal decomposition of ClCF2CO2Na and the unsuccessful capture of :CF2 with an alkene or alcohol during the olefination reaction [20]. Very recently, the successful preparation of (triphenylphosphonio)difluoroacetate

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

• Buchwald’s procedure for the catalytic asymmetric vinylation of enones [51]. However, the desired vinylated product could not be obtained under the described conditions. An alternative α-formylation/Wittig olefination sequence gave only low yields. O’Brien et al. [41] described the failure of a direct

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

• (88, see Scheme 11) and tremulenediol A (89), isolated from a fungal pathogen [84]. Horner–Wadsworth–Emmons olefination of the starting ketone 80 [85] provided an E/Z-mixture of α,β-unsaturated ester 81. Deprotonation followed by an acidic quench resulted in deconjugation to give β,γ-unsaturated ester

• formal [4 + 3] cycloaddition [82]. Starting from 4-methoxyphenol (90) Friedel–Crafts acylation and cyclization provided bicycle 91. Wittig olefination furnished benzofuran 92. Diazotransfer using p-ABSA yielded the crucial diazo compound 93, which was used in the following enantioselective

• vinylcarbenoid 120, which underwent cyclopropanation with the added olefin 118 to give bicycle 121 in decent yield. Double deprotection followed by selective acetal-protection of the less hindered alcohol and oxidation of the remaining unprotected alcohol moiety led to aldehyde 122. Wittig olefination resulted

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• -selectivity (Table 1, entry 20). Olefination of Garner’s aldehyde Olefination of 1 provides an easy access to chiral 2-aminohomoallylic alcohols A (Scheme 24). The intermediate can be derivatized further, thus providing a route for greater molecular diversity. Diastereoselective dihydroxylation of A with OsO4

• conjugate addition [93], and a recent synthesis of lucentamycin A was achieved using this strategy [94]. Epoxidation of A leads to a highly functional intermediate C, which has been used in the synthesis of manzacidin B [95]. Among the plethora of olefination reactions, the Wittig [96][97] and Horner

• –Wadsworth–Emmons [98][99][100] reactions are most commonly used for the introduction of a double bond to Garner’s aldehyde 1. Two things need to be considered before performing the olefination reactions: 1) epimerization of the stereocenter in the aldehyde (i.e. basicity vs nucleophilicity of the