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

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• stereocenters. The crucial (2Z,4E)-configuration of the diene moiety was constructed via Still–Gennari olefination [31] or via RCM of an acrylate with an E-configured diene at the opposite terminus [32]. Curvulide A has, to the best of our knowledge, not been synthesized previously. Results and Discussion We

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• product [13][14][15][16][17]. A vinyl ether is a common and versatile building block in organic synthesis as well as polymer chemistry. Typical methods for the preparation of a vinyl ether involve elimination, olefination of esters, addition of alcohols to alkynes, as well as transition metal-mediated

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• between 2-(1H-indol-1-yl)anilines and aromatic aldehydes [38]. (c) Pd-catalyzed regioselective C–H olefination/cyclization sequences from indole-substituted anilines and electron-deficient terminal alkenes [37]. However, these methods require expensive metal catalysts, long reaction time and produce only

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• intermediate 4. This spiroketal compound is logically traced back to ketone 5, which can be further divided in the vicinity of the C22 carbonyl group into two readily accessible building blocks 6 and 7. For the construction of the octalin fragment we planned to use two sequential olefination reactions followed

• PMB-protected 3-hydroxypropanal via Horner–Wadsworth-Emmons olefination, reduction to the allylic alcohol and Sharples epoxidation [8] (Scheme 2). Subsequent Cu-catalyzed epoxide-opening using methylmagnesium bromide [9] produced an inseparable mixture of 1,2- and 1,3-diol products, which upon

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• as an advanced intermediate for the synthesis of pumiliotoxin 251D [12]. Later on, Nubbemeyer and co-workers used the Horner olefination to convert 5 and its diastereomer into (+)-PTX 251D (2) and the 8-epimer of PTX 209F (4), respectively [17]. Recently, (8S,8aS)-5 has been used for the synthesis of

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• olefination. Installation of the phosphonate and desilylation gave 76, which, after oxidation, reacted in the presence of sodium 2,2,2-trifluoroethanol (NaOTFE) in 2,2,2-trifluoroethanol (TFE) via an intramolecular Horner–Wadsworth–Emmons reaction to 77. Cytochalasin L-696,474 (78) was obtained from 77 via

• accomplished within 6 consecutive steps. Generation of the dienamine 244 with pyrrolidine in methanol at 60 °C triggered an intramolecular Diels–Alder reaction to provide the full carbon skeleton 245. The final transformations of the synthesis involved a Wittig olefination of the ketone and a

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• envisaged deoxygenation route (Scheme 2), this key transformation saved 2 steps and paved the way for a final reaction sequence that was based on our synthesis of (−)-englerin A (5) [6]. Thus, Wittig olefination of the acetyl group in 3 afforded the sensitive vinyl epoxide 10 along with some cyclized

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• , Hiratsuka 259-1293, Japan 10.3762/bjoc.9.228 Abstract Symbiodinolide is a polyol marine natural product with a molecular weight of 2860. Herein, a streamlined synthesis of the C79–C97 fragment of symbiodinolide is described. In the synthetic route, a spiroacetalization, a Julia–Kocienski olefination, and a

• Sharpless asymmetric dihydroxylation were utilized as the key transformations. Keywords: Julia–Kocienski olefination; polyol marine natural product; Sharpless asymmetric dihydroxylation; spiroacetalization; symbiodinolide; Findings A 62-membered polyol marine natural product, symbiodinolide (1, Figure 1

• Julia–Kocienski olefination as the coupling reaction. The new retrosynthetic analysis of the C79–C97 fragment 8 is described in Scheme 2. We envisaged that the diol 8 could be synthesized by the Julia–Kocienski olefination [12][13][14] between aldehyde 9 and 1-phenyl-1H-tetrazol-5-yl (PT)-sulfone 10 and

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• sensitive to strong base as well as hydrogen abstraction [10][11]. While classical methods for the preparation of 1,4-dienes include partial reduction of alkynes and carbonyl olefination, a variety of transition-metal-mediated processes have been developed for the synthesis of skipped dienes of varied

• fragment. However, due to keto–enol tautomerization, carbonyl olefination methods are of limited utility for this substrate. Instead, the ketone was protected as the mixed S,O-ketal and reduced to the diol 17. Protection of the hydroxy groups and removal of the ketal afforded ketone 19. A number of

• alternative promoters were investigated to avoid the use of mercury(II) salts in the ketal deprotection (including MeI, H2O2, AgClO4/I2); however, these generally led to concomitant removal of the TBS groups. Ketone 19 was converted to the α,β-unsaturated ester 20 using the Peterson olefination [32

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• recently described a one-pot organo-catalyzed synthesis of N-heteroarylmethylene pyrrolidines 4 [13] from readily available aldehydes 1 and imine 2 by a sequence of Mannich coupling [14][15][16][17][18][19][20][21][22][23][24], Wittig olefination with phosphonium 3, and proton-mediated hydroamination

• -heteroaromatic scaffolds is reported. Based on the isomerization of pyrrolidines prepared by a simple and efficient sequence of Mannich/Wittig olefination/hydroamination reactions, no oxidant or metallic salts were employed [31]. This study also led us to investigate the feasibility of this process with

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• dithioketal 14 (86% yield) [72][73][74]. Wittig olefination of the C-1 ketone with methoxymethylenetriphenylphosphine [75] yielded the corresponding enol methyl ether, which was hydrolyzed to the aldehyde under acidic conditions and reduced with NaBH4 to form alcohol 15 with desired diastereoselectivity at

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• acetonide formation provided 7, and ozonolysis afforded Ichihara’s aldehyde 8 (Scheme 3). Interception of this intermediate thus constituted a formal synthesis; the precedent for the C8–C9 olefination involved a classical, three-step Julia olefination sequence [24]. To demonstrate proof-of-concept for a

• more step-efficient endgame, test substrates were prepared for exploration of a modified Julia olefination [32]. As shown in Scheme 4, the phenyltetrazole heteroaromatic core in sulfones 9a and 9b provided excellent E-/Z- selectivity for formation of the C8–C9 olefin under typical modified Julia

• the synthesis of alternaric acid. Three-component coupling with a vinyl nucleophile and elaboration to Ichihara’s aldehyde. Modified Julia olefination as a step-efficient alternative endgame strategy. Three-component coupling with an allyl nucleophile and demonstration of successful ruthenium

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• access ylides [26], although phosphonium ylides for carbonyl-olefination chemistry are usually prepared by deprotonation of phosphonium salts [1][2][3][4]. In fact, phosphine trapping of lithium carbenoids followed by carbonyl olefination has been little studied since Seyferth and Wittig independently

• their utility in Wittig–Schlosser and SCOOPY-type stereoselective olefination reactions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Here we have shown a new and concise method to such valuable intermediates, directly from readily available terminal epoxides. Significantly, the

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• well known [25][26]; however, we selected stereoselective olefination through deprotonation of 10 with LDA followed by the addition of phenylselenyl bromide [27] and subsequent oxidative elimination of the resulting phenylseleno group with m-CPBA according to our previous report [28], which gave E

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

• Mukund G. Kulkarni,
• Mayur P. Desai,
• Deekshaputra R. Birhade,
• Yunus B. Shaikh,
• Ajit N. Dhatrak and
• Ramesh Gannimani

Beilstein J. Org. Chem. 2012, 8, 1725–1729, doi:10.3762/bjoc.8.197

• important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene

• -carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure. Keywords: acetal; Claisen rearrangement; oxidative cleavage; ring-closure; Wittig olefination; Introduction

• method for the synthesis of 3-methylquinoline-4-carbaldehyde. It was considered that a properly substituted 2-(2-nitrophenyl)pent-4-enal [25][26][27] could be a fitting intermediate for this purpose. Such an intermediate is easily accessible through the Wittig-olefination–Claisen-rearrangement protocol

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• reaction is a modification of the Wittig olefination in which a phosphoryl-stabilized carbanion reacts with an aldehyde or ketone to form an alkene and a water-soluble phosphate ester [23][24][25]. In general, this reaction preferentially gives more stable E-disubstituted alkenes, although several

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• epoxidation, aziridination and olefination reactions [12][13] are common reaction channels. The intramolecular formation of sulfonium ylides from α-diazocarbonyl compounds tethered with alkylthio or arylthio groups has been studied by the research groups of Davies [14], Moody [15], and West [16]. From α-diazo