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

• schisanwilsonene A (126, see Scheme 15), isolated from Schisandra wilsoniana [111], a plant used in traditional chinese medicine. Submission of 1,6-enyne 116 to cationic gold-catalyst 117 led to 5-exo-dig cyclization and intermediate formation of bridged bicycle 119. Subsequent 1,5-acyl-shift afforded

• . Toste and coworkers [205] discovered a 1,2-pivaloyl shift and cyclopropanation of the resulting gold-carbenoid from 258 with enyne 259 to yield vinylalkynecyclopropane 260. This compound was shown to undergo a gold catalyzed DVCPR to yield 261. Note that this reaction does most likely proceed via a step

• 1,2-migration and subsequent formation of cis-divinylcyclopropane 269 yielding bridged bicycle 270. Chung and coworkers [210] discovered a related reaction pattern using platinum(II) as the catalyst. Depending on the attached rests on enyne 276 both possible cycloheptadienes (bridged 277 or annulated

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• Abstract The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1) is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11

• . Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial reduction and ester hydrolysis then gave resolvin D2 (1). Keywords: catalysis; eicosanoid; natural product

• followed by partial reduction. This is similar to the endgame of the reported syntheses of 1 [5][9] but both of these approaches involved formation of the C9–C10 bond as the convergent step. In our approach, 1 could arise from enyne 3 and vinyl iodide 4 which could both be obtained by Wittig extension

One-pot cross-enyne metathesis (CEYM)–Diels–Alder reaction of gem-difluoropropargylic alkynes

• Santos Fustero,
• Paula Bello,
• Javier Miró,
• María Sánchez-Roselló,
• Günter Haufe and
• Carlos del Pozo

Beilstein J. Org. Chem. 2013, 9, 2688–2695, doi:10.3762/bjoc.9.305

• Institut, Westfälische Wilhelms-Universität, Corrensstraße 40, D-48149 Münster, Germany 10.3762/bjoc.9.305 Abstract Propargylic difluorides 1 were used as starting substrates in a combination of cross-enyne metathesis and Diels–Alder reactions. Thus, the reaction of 1 with ethylene in the presence of 2nd

• for the creation of carbon–carbon bonds has exponentially increased, due to the availability of well-defined catalysts [1][2][3]. Particularly, enyne metathesis (EYM) is a powerful synthetic tool for generating 1,3-dienes by redistributing unsaturated functionalities between an alkene and an alkyne

• ]. The intramolecular version of this process, the ring closing enyne metathesis (RCEYM) reaction, has found wide application, and several examples can be found in the literature [12][13]. However, the intermolecular version, i.e. the cross-enyne metathesis (CEYM) reaction, has been much less exploited

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

• 11d (R1 = H and R2 = Me) were converted to benzothiophenes 12c and 12d in 82% and 95% yield, respectively. The synthesis of substituted hydrindene 12e was also achieved in 85% yield from monosubstituted enyne 11e (R1 = Ph, R2 = H). Substituted enynes bearing heterocycles such as indole 11f (R1 and R2

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• /AgClO4] (5/15 mol %) furnished corresponding functionalized pyrrolidines in good yields and moderate stereoselectivity (Scheme 22) [58]. The preferred alkene activation versus allenes was recently observed in the cascade 1,3-migration/[2 + 2] cycloaddition of 1,7-enyne benzoates (Scheme 23) [59]. When 83

• with simple ketones. Proposed reaction mechanism for the intramolecular [Au(I)]-catalyzed hydroalkylation of alkenes with ketones. Tandem Michael addition/hydroalkylation catalyzed by [Au(I)] and [Ag(I)] salts. Intramolecular [Au(I)]-catalyzed tandem migration/[2 + 2] cycloaddition of 1,7-enyne

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 observed. In addition, the conjugate enyne could undergo this reaction, giving the interesting electron-rich conjugated diene (6d). In some cases, thermodynamically more stable internal alkenes were also observed along with the kinetic product terminal alkene, likely through olefin isomerization

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• aromatic ring or an alkenyl group at the C7-position of the 1,6-enyne the cyclization results almost completely selective via the 6-endo mode (Table 2, entries 2,3 and entries 6,7). However, in the case of halogen-containing aromatic substituents at C7 the formation of the corresponding products 3 or 8

• ). On the other hand, the reaction of trimethylsilyl-substituted enyne 1j did not proceed at all (Table 2, entry 10), whereas the presence of a phenylthio group as an R substituent mainly afforded the corresponding 6-endo product 7k although the reaction was significantly slower (Table 2, entry 11). As

• expected [10][11][12] the terminal enyne 1l (R = H) underwent exclusively the 5-exo cyclization leading to the corresponding alcohol 8l in 55% yield (Table 2, entry 12). At this point we wondered if the cyclization would be diastereoselective, so we prepared enynes 1m by reacting 2-(phenylethynyl

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

• Motoki Naka,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2013, 9, 2182–2188, doi:10.3762/bjoc.9.256

• solved for complete mechanistic understanding of the process depicted in Scheme 1. For clarification of the reactivity of (E)-1 on deprotonation, enyne 4 was used as a model because, after trapping the vinylic anionic species by appropriate electrophiles, comparison of the yields of the resultant

• and limitation of this procedure were investigated. A number of carbonyl compounds were employed as electrophiles for the anions generated from the enyne 4. Benzaldehydes with electron-donating (Table 2, entries 2 and 3) as well as -withdrawing (Table 2, entry 4) substituents at the para position were

• of peaks was possible for the two vinylic protons Ha and Hb in the enyne 4 at δ 6.15 (qd, J = 6.6, 15.9 Hz) and 6.48 (qd, J = 2.4, 15.9 Hz), respectively (Figure 1 and Supporting Information File 1). On the other hand, relatively complex peaks were detected from the crude deuterated mixture due to

Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

• Jungho Jun,
• Hyu-Suk Yeom,
• Jun-Hyun An and
• Seunghoon Shin

Beilstein J. Org. Chem. 2013, 9, 1724–1729, doi:10.3762/bjoc.9.198

• + 2 + 2] reactions with alkenes [6]. On the other hand, Shin and co-workers have adopted propiolic acids and alkynyl sulfones for formal enyne cross metathesis (f-EYCM) [5]. These examples allow for an effective alkyne–alkene coupling under mild reaction conditions (rt) with as little as 1.5 ~ 2 equiv

• = di-t-butyl-o-biphenylphosphine, JohnPhos) formed in situ was used as catalyst, the reaction was more efficient in chlorinated solvents rather than polar aprotic or aromatic hydrocarbon solvents (Table 1, entries 1–7). Contrary to the previous [4 + 2] cycloaddition, formal enyne cross metathesis or [2

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

• construct the C9−C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1−C9 has been synthesized in high yield and

• . When a 1,3-enyne is coupled with simple epoxides, however, >95:5 regioselectivity is observed for C–C bond formation distal to the pendant alkene [18]. In conjunction with the nickel-catalyzed fragment coupling, we wished to investigate whether it would be possible to delay introduction of the

• potentially sensitive 1,4,7-triene by masking it as a cyclopropyldiene, then unveiling the skipped triene portion via a 1,5-hydrogen rearrangement (Figure 3). This strategy would allow us to take advantage of the high regioselectivity in enyne–epoxide reductive coupling reactions. Furthermore, the proposed

Preparation of optically active bicyclodihydrosiloles by a radical cascade reaction

• Koichiro Miyazaki,
• Yu Yamane,
• Ryuichiro Yo,
• Hidemitsu Uno and
• Akio Kamimura

Beilstein J. Org. Chem. 2013, 9, 1326–1332, doi:10.3762/bjoc.9.149

• 10.3762/bjoc.9.149 Abstract Bicyclodihydrosiloles were readily prepared from optically active enyne compounds by a radical cascade reaction triggered by tris(trimethylsilyl)silane ((Me3Si)3SiH). The reaction was initiated by the addition of a silyl radical to an α,β-unsaturated ester, forming an α

• cyclization process is also an interesting synthetic reaction that often provides an efficient method [11][12][13]. Recently, we reported a new type of higher-order radical cascade reaction between chiral enyne compounds and Bu3SnH, which is recognized as a useful reagent in radical reactions [14]. In this

• treatment of chiral enyne compounds. A good trans-selectivity was observed in the reaction. Results and Discussion We examined the cascade process using optically active enyne precursor 1a, which was prepared by a Michael/aldol domino reaction to chiral sulfinimines followed by thermal elimination and N

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

• starting from trivial enyne 5 and oxidation of the protected alcohol in the side-chain of cyclopentenone 6 directly into carboxylic acid 7 by using Jones’ reagent. The second key step, namely the conversion of benzoate 8 into tetracycle 10, involves the concurrent formation of two rings and two adjacent

• ]. In the sequence displayed in Scheme 18, the addition–cyclisation of a malonyl radical to enyne 89 furnishes allenyl acetate 91 by cyclisation of propargyl radical 90 [41]. Compound 91 readily undergoes reductive dexanthylation and solvolysis into enone 92, and internal Michael addition to give

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• reagents (Scheme 54) [147]. They assumed that the active species were organocuprates and that the radical character of carbocupration enabled bulky sec- or tert-alkylmagnesium reagents to be employed. Chromium-catalyzed carbomagnesiation of 1,6-diyne (Scheme 55) [148] and 1,6-enyne (Scheme 56) [149] also

• methallylmagnesium reagent would give 5l efficiently. The reaction of 1,6-enyne also proceeded through a tetraallylchromate complex as an active species (Scheme 56). However, the second cyclization did not take place. Conclusion We have summarized the progress in transition-metal-catalyzed carbomagnesiation and

Highly stereocontrolled synthesis of trans-enediynes via carbocupration of fluoroalkylated diynes

• Tsutomu Konno,
• Misato Kishi and
• Takashi Ishihara

Beilstein J. Org. Chem. 2012, 8, 2207–2213, doi:10.3762/bjoc.8.249

• group into an anisyl group in R1 resulted in a significant increase of the yield from 74% to a quantitative yield. In this case, it was found that 4b was slightly thermally stable, compared to 4a, while it could not be isolated in a pure form. In the case of the enyne having an n-C6H13 group as R1, on

• the other hand, the starting material was not completely consumed, and an inseparable mixture of the desired diyne 4c and the enyne 3c was given (Table 2, entry 3). In addition, the reaction proceeded very sluggishly in the enyne having CH2OBn as R1, and neither 3d nor 4d could be obtained in high

• yields (Table 2, entry 4). Interestingly, the enyne 3e having a CMe2OBn group as R1 was found to be a good substrate, the desired diyne 4e being obtained quantitatively (Table 2, entry 5). Additionally, 4e was so thermally stable that it could be obtained in 95% isolated yield after the silica-gel column

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• reaction. In this case the diketone 107 was obtained by a Zn/Cu-couple-induced coupling reaction between excess phenacyl bromide (105) and the enyne 106 (Scheme 27) [83]. Besides 107 its diyne and propargylallene dimers were produced, requiring a chromatographic separation of the product mixture. The

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• ) and related variants such as alkyne and enyne metathesis [36][37]. Related reactivity is prevalent for other Mδ+═Eδ− species such as imides and nitrides. Bergman's bis(cyclopentadienyl)zirconium(IV) imides, described above, will add alkenes and alkynes in [2 + 2] fashion across the Zr═NR bond (Scheme

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

• cycloisomerizations of diynyl o-benzaldehyde substrates to access novel polycyclic cyclopropanes are reported. The reaction sequence involves initial Cu(I)-mediated cycloisomerization/nucleophilic addition to an isochromene followed by diastereoselective Pt(II)-catalyzed enyne cycloisomerization. Keywords: chemical

• catalysts that effected cycloisomerization of 3 to alkynyl isochromene 5, which is an interesting enyne substrate with potential for further reactivity [9][10]. In the reaction screen of alkynyl benzaldehyde substrate 3, we found that in the absence of optimization Cu(MeCN)4PF6 [11][12][13] afforded the

• highest isolated yield of 5 (60%) (Scheme 2). As the production of isochromene 5 offered a unique opportunity for additional cycloisomerization processes, we elected to explore this manifold of reactivity. Based on reports by Echavarren and co-workers [14][15], we treated enyne 5 with PtCl2 at 80 °C in

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

• glycals using several aromatic and aliphatic alkynes. This Pd-catalyzed cross-coupling reaction presents a facile access to alkynyl C-glycosides and sets the stage for a reductive/oxidative refunctionalization of the enyne moiety to regenerate either C-glycosidic structures or pyran derivatives with a

• substituent in position 2. Keywords: C-glycosides; enyne; glycals; reductive/oxidative refunctionalization; Sonogashira–Hagihara reaction; Introduction Carbohydrates are key players in a plethora of biological processes, such as cell-development, metastasis, cell–cell aggregation and viral infection [1][2

• crucial part of the solvent mixture, otherwise no reaction was observed. Interestingly, when we employed the perbenzylated enyne 9ea the yield of the alkyne-reduced product decreased tremendously. A mixture of completely reduced products was obtained. Thus, we assume that not only electronic effects, but

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

• , the group of Echavarren has recently developed a formal (2 + 2 + 2) gold-catalyzed synthesis of interesting oxa-bridged bicyclo[5.3.0]decanes from 1,6-enyne precursors equipped with an appropriately tethered carbonyl group (27, Scheme 16) [66]. In these processes, the carbonyl acts as a nucleophile

Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene

• Alexandre Pradal,
• Chung-Meng Chao,
• Patrick Y. Toullec and
• Véronique Michelet

Beilstein J. Org. Chem. 2011, 7, 1021–1029, doi:10.3762/bjoc.7.116

• [53][54][55], we selected 4-MeO-3,5-(t-Bu)2-MeOBIPHEP-(AuCl)2 complex [56][57][58] as the best candidate for such a transformation. Initial experiments were performed using N-tosyl allyl substrate 1a and oxygen-linked propargylic 1,6-enyne 2a as model substrates (Table 1). The reaction of 1a was

• studies. Synthesis of 1,6-enynes We prepared various oxygen-tethered 1,6-enynes according to classic methodologies employing a Williamson alkylation reaction and/or a Sonogashira cross-coupling [60][61] (Scheme 2 and Scheme 3). The known enyne 5 [62][63] was engaged in Pd-catalyzed coupling in the

• presence of diversely functionalized aryl iodides (Scheme 2). The corresponding substituted alkynes 2b–e [46] were isolated in 71–85% yield. An analogous 1,6-enyne 6 [64] was also reacted with 3-bromoiodobenzene under the same reaction conditions and led to the formation of substrate 2f in 58% isolated

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

• large substituents at the alkyne terminal position did not affect the efficacy of the reaction. Intermolecular cycloaddition/Au(I)-catalyzed cyclization of aryl acetylene dienes 33–35 provided the desired ketones 37–39 in yields ranging from 68 to 91% (Table 2, entries 1–3). Remarkably, enyne 36 was

Intramolecular hydroamination of alkynic sulfonamides catalyzed by a gold–triethynylphosphine complex: Construction of azepine frameworks by 7-exo-dig cyclization

• Hideto Ito,
• Tomoya Harada,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2011, 7, 951–959, doi:10.3762/bjoc.7.106

• enyne cycloisomerizations. The new catalytic system has expanded the scope of the reactions to six- and seven-membered ring formations, which had been difficult with the conventional catalytic systems [55]. Furthermore, we found that L1–gold(I) complex efficiently catalyzed the cyclization of internal

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

• from suitably substituted (Z)-2-en-4-yn-1-ols 5 [20]. A similar strategy has been applied to an efficient formation of substituted furans 9 through gold-catalyzed selective cyclization of enyne-1,6-diols 8 [21]. Nucleophilic attack of the hydroxy oxygen atom on 1-position to a gold-coordinated C–C

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• been described by Fairlamb [82]. We were also able, from compound 2, to develop a 1,5-enyne metathesis that leads to functionalized cyclobutenes 38 (Scheme 20) [83], which was subsequently nicely illustrated by Goess in a total synthesis of grandisol [84]. From isoxazolines 23, we were also able to

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• displays the possibility of diverse product creation through the use of either gold- or iodonium-triggered heterocyclizations. Carbocyclizations with 1,5-enynes Within the rapidly developing area of gold-catalysis, enyne cycloisomerizations have been particularly well studied [76][77][78][79][80][81][82

• ) activated by AgSbF6 (Scheme 7) [91]. A 1,5-enyne disubstituted at the terminal carbon of the alkene (e.g., 19) leads to a very selective 5-endo carbocyclization where no side products resulting from 5-exo or 6-endo modes were observed. A mechanism was proposed involving a cationic intermediate after

• ]. This reaction proceeds via an exceptional 5-endo halocyclization, which likely results from the stability of the tertiary carbocation, since only H at the C1-position rendered the enyne unreactive under the conditions used (excess NIS, CH2Cl2 at reflux). From a synthetic point of view, the development