N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• concentrations [10][11][12]. An alternative route is a two-step reaction via N-allylation and further Prilezhaev epoxidation with peroxides [13][14][15]. The solubility of hydrophobic reactants in water can be increased significantly by cyclodextrins (CD) and thereby the use of organic solvents can be reduced

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• propellane derivatives involves a Weiss–Cook condensation, a Fischer indole cyclization, and a ring-closing metathesis as key steps. Keywords: allylation; indole derivatives; propellanes; ring-closing metathesis; Weiss–Cook condensation; Introduction Propellanes are tricyclic systems conjoined with carbon

• unsymmetrical diindole derivatives can be generated. Therefore, mono-allyl derivative 7 was subjected to a second allylation with allyl bromide to generate the diallyl diketone 3 (86%) (Scheme 2). The second allyl group is also placed from the convex side of the molecule. Later, the mono-allyl diketone 7 was

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• (35% overall yield from 3). A second set of F-ring-modified exo-cyclopamine derivatives was obtained starting from previously described 12-ß-triethylsilyloxy compound 10 (see Scheme 2) [32]. To construct the spirolactone 12, a three-step process consisting of (1) allylation (allylcerium chloride, THF

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• allylation/intramolecular hydroalkoxylation sequence. The reaction is mild, practical and tolerant of a wide variety of substituents on the phenol. Keywords: allylic alcohols; chromans; Friedel–Crafts; gold catalysis; heterocycles; Introduction Chromans (dihydrobenzopyrans) are important and ubiquitous

• structural motifs found in a variety of important biologically active natural products such as vitamin E and flavanoids [1][2][3][4][5]. One approach towards chromans [6][7][8][9][10][11][12], which is biosynthetically inspired, is the Friedel–Crafts allylation [13] of phenols followed by cyclisation of the

• Friedel–Crafts allylation of phenols has been reported by Chan and co-workers [73], there have been no reports on the direct synthesis of chromans [74] using gold catalysis [75] with phenols and allylic alcohols prior to our example shown in Scheme 1. Since the reaction is very practical: distilled

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

• demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10−C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted

• using a route analogous to one reported by Smith [38]. Allylation of 24 with (+)-B-allyldiisopinocampheylborane generated the alcohol 25 in high yield and enantioselectivity. Directed epoxidation using VO(acac)2 and tert-butyl hydroperoxide was initially performed in order to furnish 27 directly

• coupling, oxy-Michael addition to an enone, and iodocyclization methods. Fluoride-promoted decarboxylation of TMSE esters was identified as a mild strategy enabling simple aldol reactions for the construction of the C15−C16 bond. Allylation and reductive decyanation of a lithiated cyanohydrin acetonide was

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• , monothioacetalization and allylation of hemiacetals. The reactions, which take place under mild conditions and at low catalyst loadings, can be conducted using hemiacetals, the corresponding O-silyl ethers, and, in some cases, the acetal dimers. Aldehydes react under similar conditions to furnish good yields of

• dithioacetals. Reactions of hemiacetals with nitrogen nucleophiles are unsuccessful. 1,2-Dioxolan-3-ols (peroxyhemiacetals) undergo Re(VII)-promoted etherification but not allylation. Hydroperoxyacetals (1-alkoxyhydroperoxides) undergo selective exchange of the alkoxide group in the presence of either Re2O7 or

• a Brønsted acid. Keywords: allylation; hemiacetal; O,O-acetal; O,S-thioacetal; peroxyacetal; Re2O7; S,S-acetal; Introduction The synthetically important conversions of hemiacetals to acetals, thioacetals, or homoallyl ethers are typically achieved through activation of the substrate with a strong

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• hydroxamate ester as a chiral Lewis acid coordination moiety was first shown in an intermolecular reaction involving a radical addition and sequential allylation processes. Next, the effect of hydroxamate ester was studied in the cascade addition–cyclization–trapping reaction of substrates with a carbon

• –allylation of hydroxamate esters 3A–C having an acryloyl moiety (Scheme 1). The reactions were evaluated in CH2Cl2 at −78 °C by employing isopropyl iodide, allyltin reagent, and Et3B as a radical initiator. The enantiomeric purities of products were checked by chiral HPLC analysis. The effect of the

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

• –Miescher ketones represent two of the most famous examples [59][60][61][62][63][64][65]. With this background information in mind, we devised an enantioselective synthesis of 8 starting from commercially available dione 12, and the synthesis of 8 was previously published [25][26]. Tsuji–Trost allylation

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• a benzofuran or an indole core. Our first study involved the cyclization of allyl moieties such as allyl ether 1a or N-allyl protected anilines 1b–c, easily prepared by quantitative allylation of o-iodophenol and o-iodoanilines using allyl bromide in DMF (Scheme 1). Following the protocol optimized

• electroreductive allylation of aromatic or heteroaromatic halide and allylic acetate [28][29] was successfully carried out using nickel-bipyridine complexes as catalysts in DMF. More recently, Weix noted that the same reaction could be achieved under chemical conditions, always using bi-(or ter-)pyridine nickel

• catalysts [30]. These data explain the formation of 9a. Finally, the 8a/9a ratio suggests that 5a-Ni can undergo two competitive pathways: the 5-exo-trig cyclization leading to 7a-Ni, and the aromatic allylation affording 9a. Based on the figures we conclude that 5a-Ni reacts more rapidly with the allyl

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• processes. Keywords: amidyls; iminyls; radical allylation; radical vinylation; xanthate transfer; Introduction Natural products exhibit an astonishing diversity of molecular architectures and structural complexity. This has spurred the development of numerous synthetic strategies for the rapid assembly of

• provide a very broad diversity of structures. Radical vinylations and allylations Xanthates may be incorporated into radical processes of various kinds. Vinylation and allylation reactions are particularly appealing, in view of the importance of such transformations in organic synthesis. A number of

• normal addition–transfer of a xanthate to an alkene with the allylation process to give fairly elaborate compounds, such as 140 obtained by reaction of adduct 138 with sulfone 139 [56]. It is interesting to note that both the vinylation and the allylation reactions are applicable to aliphatic iodides, as

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• allylation product of 4, whereas for the generation of 17 we have to assume that its precursor monoanion has the propargyl structure 16. In all these structures the lithium atom is only meant to mark the position of the carbon atom at which the electrophile attacks; no proposition about the nature of the

• carbon–lithium bond or the structure of the anion is intended. Further allylation of 14 under the reaction conditions and formation of the symmetric bisallyl derivative of 2, hydrocarbon 15, was not observed. On the other hand, metalation of 17 to the monoanion 18 and its reaction with allyl bromide (13

• -yielding synthetic transformations from simple substrates, are useful starting materials for the preparation of a plethora of novel organic compounds. The alkylated conjugated bisallenes 1– 3 as model systems for polar reactions. Alkylation and silylation of 2. Allylation of the monoanion 4. Metalation

Stereoselective synthesis of tetrasubstituted alkenes via a sequential carbocupration and a new sulfur–lithium exchange

• Andreas Unsinn,
• Cora Dunst and
• Paul Knochel

Beilstein J. Org. Chem. 2012, 8, 2202–2206, doi:10.3762/bjoc.8.248

• 25 °C for 8 h produces the intermediate copper reagent 3a, which, after allylation with allyl bromide, provides the thioether 4a in 84% yield and an E/Z ratio of 99:1 (Scheme 4). The reaction of 3a with other typical electrophiles is possible, but proceeds in moderate yields due to the low reactivity

• equiv, −78 °C, 15 min) furnishes the corresponding unsaturated ethylester 5b in 55% isolated yield and an E/Z ratio of 95:5. Finally, a copper-catalyzed allylation with ethyl 2-(bromomethyl)acrylate [37] (1.5 equiv, −78 to 0 °C, 2 h) affords the triene 5c in 55% yield and an E/Z ratio of 99:1 (Scheme 6

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• homoallyl alcohol 16. The magnesium bromide diethyl etherate mediated allylation proceeded under substrate control and with complete diastereoselectivity [23][32]. Cross-metathesis of homoallyl alcohol 16 with the unit B derived acrylamide 17 provided the α,β-unsaturated δ-hydroxy carboxamide 18 (Scheme 2

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

• the results of our continuing challenges associated with this targeted natural product on the basis of the above synthetic strategy. As a result, and in addition to improvement of the inefficient stereoselectivity observed in allylation process from 4 to 7, we established the new alternative synthetic

• (+)-batzellasides B was accomplished, considering that the synthetic route from 4 to 1b has been established previously. At this point, it was thus suggested that the remaining challenge was to improve the stereoselectivity of the allylation of 4. In the first approach of our previous work [19], we demonstrated

• more efficient synthetic method for the stereoselective allylation of 4 using an appropriate combination of allylic reagent and Lewis acid to produce the desired diastereomer 7 preferentially. Beginning with a reaction employing indium chloride (InCl3) instead of TBSOTf at 0 °C in dichloromethane, we

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• found that other protecting groups were either not compatible with the reaction conditions towards acetonide 15 or were found to be impossible to cleave afterwards while leaving the rest of the molecule intact. Since we were unable to conduct a selective mono-allylation of the hydroxy group in the 4

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• % ee of the (E)-allylation products and 92% ee of the recovered Morita–Baylis–Hillman adducts. These intriguing results stimulated us to further develop the axially chiral oxazoline–carbene ligands 7 with an N-naphthyl framework and to evaluate their coordination with AuCl·SMe2. Results and Discussion

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• publication, we demonstrated the scope of the methodology over a range of ortho-lithiation benzyne precursors. To establish that any one of these precursors could be used to form quaternary adducts, we subjected the benzylation conditions to precursor 2b and the allylation conditions to precursor 2c

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• reagents 5 and 8 are obtained at 25 °C in quantitative yield. The allylation of pyridylzinc derivative 8 with allyl bromide provides pyridine 9 in 85% yield [6]. Interestingly, a diiodide, such as 2,5-diiodothiophene (10) reacts selectively with Zn and LiCl to provide the iodothienyl ketone 11 in 94% yield

• after benzoylation. Subsequent treatment of 11 with a second amount of Zn and LiCl (1.4 equiv) provides a new intermediate zinc reagent within 10 min, which after allylation provides the 2,5-disubstituted thiophene 12 in 87% yield (Scheme 3) [6]. The insertion reaction proceeds best with aryl and

• -coupling (Negishi reaction) affords the 5-arylated furan 15 in 89% yield. Interestingly, a high chemoselectivity is observed with several heterocyclic dihalides [8][9]. Thus, the tribromopyrimidine 16 provides only the 4-zincated pyrimidine 17. After allylation, the expected allylated pyrimidine 18 is

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• the gold-catalyzed intramolecular allylation of 1.a Supporting Information Supporting Information File 172: Experimental details and characterization of the synthesized compounds. Acknowledgment Acknowledgment is made to Progetto FIRB “Futuro in Ricerca” Innovative sustainable synthetic

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• catalytic amount of phosphite–gold(I) pre-catalyst and a silver additive. Notably, the addition is regioselective for the allene terminus, and generates (E)-allylation products 202. The direct C–H functionalization of indoles or pyrroles is an efficient method for the introduction of vinyl and aryl groups

Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

• Peter Wipf and
• Marija D. Manojlovic

Beilstein J. Org. Chem. 2011, 7, 824–830, doi:10.3762/bjoc.7.94

• intermediates can be transmetalated in situ with dimethylzinc or zinc chloride, which facilities the cross-coupling process to give N-unprotected homoallylic amines after aqueous workup. All products were isolated as single regio- and diastereoisomers, and the regioselectivity of the allylation step was shown

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• 69 provides an attractive starting point since it reacts with organometallic reagents with a high degree of diastereoselectivity and minimal racemization. N-allylation (allyl iodide/NaH; 95% yield) of an intermediate derived from 70 gave the diolefin product 71, which was then subjected to RCM

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

• Benan Kilbas and
• Metin Balci

Beilstein J. Org. Chem. 2011, 7, 246–253, doi:10.3762/bjoc.7.33

• formation reactions in synthetic organic chemistry have attracted considerable attention in recent years [1]. Palladium-catalyzed allylation is also a particularly useful method for the activation of allylic substrates [2]. Trost et al. described a highly stereoselective synthesis of oxazolidinone 2

Cross-metathesis of allylcarboranes with O-allylcyclodextrins

• Ivan Šnajdr,
• Zbyněk Janoušek,
• Jindřich Jindřich and
• Martin Kotora

Beilstein J. Org. Chem. 2010, 6, 1099–1105, doi:10.3762/bjoc.6.126

• carried out according to the previously reported procedures [8]. O-Allylcyclodextrins 2 were prepared by allylation of β-cyclodextrins under various reaction conditions (2I-O-allyl-β-cyclodextrin for 2a [22], 3I-O-allyl-β-cyclodextrin for 2b [23], and 6I-O-allyl-β-cyclodextrin for 2c) followed by

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• attractive precursors for organic synthesis as there are several possibilities for further transforming the exocyclic double bonds. Typically, in transition-metal-catalyzed allylation reactions reactive, metal-coordinated allyl cations are formed which may lead to linear and branched products, whereby the

• product ratio is dependent on the catalyst employed (Scheme 23). To date, only few FC-type allylations with environmentally benign allylating reagents, such as allyl alcohols have been reported. Here Shimizu and co-workers did seminal work by developing a Mo(CO)6- and W(CO)6-catalyzed allylation and

• 54b did not give the corresponding alkylated cresol 59. Instead the chromane 60 was observed in 28% yield (Scheme 25). This reaction has recently been improved and extended by applying MoCl(CO)3Cp and [Mo(CO)3Cp]2 as transition-metal catalysts [76]. A very similar FC allylation/hydroaralyation