Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• , the cyclization of cyclic enol ether 1 using σ-donor ligands such as IPr (L1) [19] was exceptionally selective for the 5-exo-dig pathway (1→2) whereas bulky Me4XPhos (L2) [12] gave mainly 6-endo-dig-cyclized product 3. Results and Discussion During the course of our investigation, we examined the

• cyclization of non-cyclic enol ethers. As expected, the cyclization of enol ether 4 using [L2AuNCMe][SbF6] in dichloromethane afforded the cyclohexene 5 in 79% yield (Scheme 2). However, the anticipated 5-exo-dig product 6 was not observed when the catalyst [L1AuNCMe][SbF6] was utilized. Instead, the

• cyclizations of the enol ether 11a (R1 = p-BrC6H4, R2 = H) gave the corresponding benzothiophene 12a in 83% yield. The use of electron-poor silyl enol ether 11b (R1 = p-NO2C6H4, R2 = H) gave the desired product 12b, albeit in lower yield of 63%. Di- and trisubstituted silyl enol ethers 11c (R1 and R2 = H) and

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• therefore leads to a stereodivergent approach to the natural product and its enantiomer. The gold-catalyzed 5-endo-cyclization affords the corresponding dihydrofurans, which after separation, azidation of the enol ether moiety and two subsequent reduction steps give the natural product and its stereoisomers

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

• with silane to regenerate the Cu-hydride. Alternatively, the Cu-enolate might enter a competing catalytic cycle by reacting with silane, furnishing a silyl enol ether and the catalytically active Cu-hydride species. The silyl enol ether is inert to protonation by tert-butanol, and therefore the

• competing secondary cycle will result in a decreased yield of reduction product. This reasoning prompted us to run the reaction in toluene without any protic co-solvent, which should exclusively lead to the silyl enol ether, and add TBAF as a desilylating agent after complete consumption of the starting

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• investigations by the groups of Mascareñas, González and Chen revealed that the gold-catalyzed cycloaddition between an allenamide and an appropriate alkene (e.g., enamide, enol ether or vinylarene) provides a variety of cyclobutanic systems in excellent yields. The optimum catalysts for the racemic processes

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

• synthesized (Scheme 8). Strategic bond disconnections revealed the common isoindolinone precursor 73. The synthesis of the latter commenced from N,N-dibenzylphenylalanine (71) to afford the Diels–Alder substrate 72 in four steps. The envisioned intramolecular Diels–Alder cyclization of the silyl enol ether 72

• provided the depicted endo-diastereomer in good yield. Exchange of the N-benzyl for a Boc-protecting group and cleavage of the silyl enol ether gave the corresponding ketone, which was first converted to an enol-triflate and then to the tricyclic alkene 73. At this stage, the syntheses of cytochalasin B

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• the ketene dithioacetal in the absence of a trapping group [21]. The anodic coupling of a carboxylic acid group with a vinyl sulfide and an enol ether were also examined (Table 2). As with earlier alcohol and amine based cyclizations, reactions with the vinyl sulfide coupling partner proceeded much

• better than did their enol ether counterparts [21][22]. In the previous cases, the argument was made that less polar radical cations underwent better trapping reactions with heteroatomic nucleophiles [23], and a similar argument can be made here. The oxidation potential for the vinyl sulfide used in

• substrate 17a is +1.08 V versus Ag/AgCl [9] and the oxidation potential of the enol ether in substrate 17b is +1.18 versus Ag/AgCl [9]. Both oxidation potentials are lower than the potential measured for the carboxylate suggesting that both reactions proceed through the olefinic radical cation. While an

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• -exo-methylenetetrahydrofuran 42 is converted into the oxonium cation 43. Subsequent capture of this intermediate 43 by a second molecule of 42 can occur via two different pathways. The first one involves the addition of the enol ether function of 42 onto 43, leading to the creation of a new C–C bond

• enol ether function, followed by 6-exo-trig cyclization, completes this sequence of events and provides the dioxane derivative 46. Interestingly, no reaction was observed when the spirocycle 41 and the dioxanes 35, 36 and 39 were reacted under acidic conditions, indicating that the final step is not

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• promoters in Diels–Alder (DA) and HDA reactions [12][13][14][15][16][17]. Regarding enantioselective processes, the majority of them have been associated with the employment of a specific Lewis acid and a selected chiral inductor connected to the enol ether moiety to furnish nonracemic nitroso acetals

• -deficient C=C bond (Scheme 3). Thus, the approach of the enol ether to the β-nitro carbon was preferred by the less hindered Si face on the opposite side to the largest group. Secondary orbital and Coulombic interactions have been proposed to explain the endo approach of the enol ethers [9][33][41]. In the

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• heptenone 12 [17][18][19][20][21]. The more thermodynamically stable silyl enol ether 13 was regioselectively formed from 12 under Holton’s conditions [22], and DDQ-mediated oxidation of 13 resulted in the formation of α,β-unsaturated ketone 14. Asymmetric reduction of ketone 14 was in turn realized by

• due to the unfavorable interaction of the two proximal TBS groups in TS-B, allowing formation of 8 as the major compound. Having synthesized the optically active 8, the next task was the preparation of C2-symmetric bicyclo[3.3.2]decene 1 from 8 (Scheme 5). The silyl enol ether formation of aldehyde 8

• compounds corresponds to that of the natural products. High-resolution mass spectra were measured on Bruker microTOFII. TMS-enol ether 13: Methylmagnesium bromide (3.0 M in Et2O, 8.5 mL, 26 mmol) was added to a solution of iPr2NH (3.9 mL, 28 mmol) in Et2O (170 mL) at 0 °C. The mixture was stirred at room

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• [11]. Chain termination is commonly carried out by using ethyl vinyl ether or cis-butene derivatives, although incomplete end-capping has been reported as a limitation with the former [12]. Notable examples include an enol ether derivative that introduces a β-trimethylsilylethoxy protected carboxylic

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• diynyl benzaldehyde 3 and dimethyl malonate is catalyzed by Cu(I) to afford isochromene 24 [20][21][22]. Pt(II) π-coordination of the pendant alkyne of 24 followed by cyclization of the enol ether affords the seven-membered-ring metal-“ate” intermediate 25. The cyclization occurs at the face opposite the

• 1,2-hydride shift to intermediate 27 followed by elimination of the metal catalyst [25] to afford the observed cyclopropane product 6. An alternative reaction pathway may be invoked for the ethyl-substituted substrate 22 leading to product 23 (Scheme 4). After initial cyclization of the enol ether

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• enynes was achieved by selective reduction of the triple bond by making use of Raney nickel (Table 3). We found that the electron-rich enol ether moiety remains untouched, when reaction times of less than four hours were chosen in the case of the enynes 9e–9h. It should be noted that methanol was a

• , overnight), whereas in the case of enyne 11b, under the same reaction conditions, only the triple bond was reduced to furnish enol ether 14e selectively. In three cases we further functionalized the 1-alkylated glycals by an epoxidation/epoxide-opening sequence [30][31][32][33]. Dimethyldioxirane (DMDO) was

• essential co-solvent in order to execute the Ni-catalyzed reduction. The enol ether double bond could be further hydroxylated by an epoxidation/epoxide opening sequence. Depending on the hydride source α- and β-configured alkyl-C-glycosides were obtained diastereoselectively in moderate yield. These

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• -dihydro-2H-1,2-oxazines. Their enol ether double bond was then subjected to a hydroboration followed by an oxidative work-up, and finally the auxiliary was removed. The described three-step procedure enabled the synthesis of enantiopure hydroxylated 1,2-oxazines. Typical examples were treated with

• reagents [33]. Here we report on the application of a nitrone with an L-erythronolactone-derived auxiliary for the synthesis of 3,6-dihydro-2H-1,2-oxazine derivatives of type D. Their selected transformations, including hydroboration of the enol ether moiety, oxidative work-up, glycosyl cleavage, and

Facile isomerization of silyl enol ethers catalyzed by triflic imide and its application to one-pot isomerization–(2 + 2) cycloaddition

• Kazato Inanaga,
• Yu Ogawa,
• Yuuki Nagamoto,
• Akihiro Daigaku,
• Hidetoshi Tokuyama,
• Yoshiji Takemoto and
• Kiyosei Takasu

Beilstein J. Org. Chem. 2012, 8, 658–661, doi:10.3762/bjoc.8.73

• on triflic imide (Tf2NH)-catalyzed reactions [8], we accidentally found that the isomerization of kinetically favourable silyl enol ethers into thermodynamically stable ones occurs smoothly in the presence of Tf2NH. When the TBS enol ether 1a was treated with a catalytic amount of Tf2NH (1.0 mol

• CH3CN (entry 6). When 10-camphorsulfonic acid (5 mol %) was used as a catalyst for 1 h, the isomerization was incomplete (entry 7). Enol ethers bearing typical silyl groups were also isomerized (entries 8–12). The decomposition of TMS enol ether 1b into 3b slightly increased at ambient temperature

• compared to that at −10 °C (entries 8 and 9). In the reaction of TIPS enol ether 1d, the reaction rate decreased and more catalyst (5 mol %) was necessary to achieve equilibrium within 5 min (entry 12). Several silyl enol ethers were explored for catalytic isomerization under the optimized conditions (1

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• is regenerated. When using a dienol silyl ether such as 21 (Scheme 12) as the diene component, the formation of the (4 + 2) products can be justified in terms of an alternative mechanism consisting of a 5-exo nucleophilic attack of the silyl enol ether moiety on the electrophilically activated alkyne

One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

• Boubacar Sow,
• Gabriel Bellavance,
• Francis Barabé and
• Louis Barriault

Beilstein J. Org. Chem. 2011, 7, 1007–1013, doi:10.3762/bjoc.7.114

• generate carbon-bridged frameworks of various sizes through a gold(I)-catalyzed carbocyclization [13]. Although the cyclization of enol ether 5 can produce 5-exo and 6-endo products, we found that gold complexes 6, having bulky phosphine ligands such as 2-bis(tert-butylphosphino)biphenyl, gave exclusively

• Diels–Alder reaction/Au(I)-catalyzed 6-endo-dig carbocyclization (Scheme 3). Cycloaddition between diene 12 and dienophile 13 should provide the endo cycloadduct 14, which, in the presence of a gold(I) catalyst, would form the gold complex A. This undergoes a carbocyclization of enol ether [24][25][26

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• , commercial reagents and additives on the oxidation of an elimination-prone Povarov tetrahydroquinoline substrate. In this way, tetrahydroquinolines 17,17' were synthesized as a mixture of isomers from the enol ether 14, p-bromoaniline (15) and p-chlorobenzaldehyde (16) under Sc(OTf)3 catalysis using standard

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• relatively unstable enol ether 12, which was then immediately treated with aqueous silica gel to give the ketone 4 in 93% yield over two steps. Formation of 12 was unambiguously confirmed by the analysis of 1H NMR data of the crude reaction mixture. From a mechanistic viewpoint, the reaction presumably

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

• opening is frequently troublesome, being governed by a number of factors. An improvement in the selectivity and efficiency of the total synthesis of (+)-1-deoxynojirimycin (62) (24% overall yield) was made by Poisson et al. [65], who developed a one-pot tandem protocol involving enol ether RCM

• hydride traps. Satisfactory results in RCM were, however, obtained from 78: in the presence of the 2nd-generation Grubbs catalyst 5 and benzoquinone in refluxing toluene, 78 was converted into the cyclized enol ether 79 in 70% yield, while with the Hoveyda–Grubbs catalyst (6, 10 mol %; benzoquinone 10 mol

Gold-catalyzed alkylation of silyl enol ethers with ortho-alkynylbenzoic acid esters

• Haruo Aikawa,
• Tetsuro Kaneko,
• Naoki Asao and
• Yoshinori Yamamoto

Beilstein J. Org. Chem. 2011, 7, 648–652, doi:10.3762/bjoc.7.76

• -induced in situ construction of leaving groups and subsequent nucleophilic attack on the silyl enol ethers. The generated leaving compound abstracts a proton to regenerate the silyl enol ether structure. Keywords: alkylation; gold catalysis; leaving group; silyl enol ether; substitution reaction

• reaction of silyl enol ethers with ortho-alkynylbenzoic acid esters which leads to the formation of α-alkylated silyl enol ethers (path b). We examined the reactions of silyl enol ether 1a with ortho-alkynylbenzoic acid benzyl esters 2 in the presence of gold catalysts under several reaction conditions and

• the results are summarized in Table 1 [18][19][20][21]. With a cationic gold catalyst, derived from Ph3PAuCl and AgClO4, the reaction of 1a with 2a proceeded at 80 °C over 2 h and the benzylated silyl enol ether 3a was obtained in 35% yield, along with the eliminated isocoumarin 4a and recovered 2a in

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• methanol. Path a, which corresponds roughly to our original experimental designs, involves initial gold-catalyzed 5-endo-dig cyclization to dihydrofuran 18. Once the regiochemistry is established, any number of condensation pathways would lead to spiroketal 17. For example, protonation of the enol ether

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• ) undergo carbocupration to give the branched product 16 in good yields and as single isomers irrespective of whatever substitutents are present on the starting alkyne 14 a,b (R = H, Me, Scheme 8) [8][9]. The vinylic organocopper 15 is more stable than the corresponding β-metalated enol ether 5a: 5a

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• -derived nitrones afforded syn- or anti-configured hydroxylamine derivatives 4a–d that were cyclized under Lewis acidic conditions to yield functionalized dihydropyrans cis- or trans-5a–d containing an enol ether moiety. This functional group was employed for a variety of subsequent reactions such as

• dihydroxylation or bromination. Bicyclic enol ether 19 was oxidatively cleaved to provide the highly functionalized ten-membered ring lactone 20. The synthesized enantiopure aminopyrans 24, 26, 28 and 30 can be regarded as carbohydrate mimetics. Trimeric versions of 24 and 28 were constructed via their attachment

• ether, dihydropyran, and dihydrofuran, all added smoothly to glyceraldehyde-derived nitrones 2a or 2b after lithiation with tert-butyllithium. Whereas in the reaction with uncomplexed nitrones, 1.5 equivalents of the respective lithiated enol ether were sufficient to obtain the desired syn-products with

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• trifluoromethylating power of chalcogenium salts increased in the order Te < Se < S while nitro-substituted reagents showed higher reactivity than non-nitrated reagents [14]. Matching the power of the trifluoromethylating agent with the nucleophile (carbanion, silyl enol ether, enamine, phenol, aniline, phosphine

One-pot three-component synthesis of quinoxaline and phenazine ring systems using Fischer carbene complexes

• Priyabrata Roy and
• Binay Krishna Ghorai

Beilstein J. Org. Chem. 2010, 6, No. 52, doi:10.3762/bjoc.6.52

• unstable enol ether 8. No aromatized product was isolated, even under mild acidic conditions. As part of a general effort to prepare aza-analogues of hydrophenanthrene natural products (including morphine alkaloids and abietanes) and tetracyclic triterpenes, the coupling of o-alkynyl pyrazine/quinoxaline