Ligand-Controlled Access to [4 + 2] and [4 + 3] Cycloadditions in Gold-Catalyzed Reactions of Allene-Dienes

Mauleón, Pablo; Zeldin, Rachel M.; González, Ana Z.; Toste, F. Dean

doi:10.1021/ja901649s

Cited by 232 publications

(102 citation statements)

References 35 publications

(27 reference statements)

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“…[6,7] Therefore, we became interested in the behaviour of furan derivatives in the presence of allenyl ethers and cationic gold(I) catalyst A. Allenyl ether 1b was allowed to react with furan under our standard reaction conditions which furnished a Mukaiyama-Micheal type 1,4-addition product 6a in 38% yield. The treatment of 2-methylfuran did not alter the reaction pattern, and 1,4-addition product 6b was obtained in a better yield (59%).…”

Section: Entries 2-5)mentioning

confidence: 99%

“…[5] However, recent re- ports show that Pt and Au complexes induce simple allene-dienes I to undergo intramolecular [2 + 2], [4 + 2] and [4 + 3] cycloaddition reactions (Scheme 1). [6] A subsequently performed DFT calculation suggested that both the [4 + 2] and [4 + 3] cycloadditions proceed through an initial gold-catalyzed concerted [4 + 3] cycloaddition of a gold-activated allene with a diene to a carbene intermediate like III. [7] The selectivity for either pathway depends on a preference for either 1,2-H or 1,2-alkyl shifts that the gold-stabilized intermediate III experiences.…”

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confidence: 99%

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Cationic Gold(I)‐Catalyzed Intermolecular [4+2] Cycloaddition between Dienes and Allenyl Ethers

Wang

Zou

et al. 2011

Adv Synth Catal

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Section: Entries 2-5)mentioning

confidence: 99%

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confidence: 99%

Cationic Gold(I)‐Catalyzed Intermolecular [4+2] Cycloaddition between Dienes and Allenyl Ethers

Wang

Zou

et al. 2011

Adv Synth Catal

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“…However with distally monosubstituted allenes like 2 the reactions usually require more stringent conditions and can lead to mixtures of isomers (B and B', Figure 2, box 2). [12,13] Moreover, at the outset, it was not clear how the presence of substituents in the diene or of stereocenters in the connecting tether could influence the efficiency and stereoselectivity of the reaction. [12][13][14] In designing the precursor, and considering that these cycloadditions are proposed to proceed through an exo-like transition state, [12] we envisioned that a bulky group in C4 such as a silyl ether (X = OSiR3), would allow the stereoselective formation of the trans-fused intermediate II, via a transition state like TS-I ( Figure 2, Box 1).…”

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confidence: 99%

“…[12,13] Moreover, at the outset, it was not clear how the presence of substituents in the diene or of stereocenters in the connecting tether could influence the efficiency and stereoselectivity of the reaction. [12][13][14] In designing the precursor, and considering that these cycloadditions are proposed to proceed through an exo-like transition state, [12] we envisioned that a bulky group in C4 such as a silyl ether (X = OSiR3), would allow the stereoselective formation of the trans-fused intermediate II, via a transition state like TS-I ( Figure 2, Box 1). Hopefully, a selective 1,2-migration of the hydrogen at C7 would allow the exclusive formation of the adduct 3, which would then be submitted to a stereoselective oxygenation.…”

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confidence: 99%

Concise, Enantioselective, and Versatile Synthesis of (−)‐Englerin A Based on a Platinum‐Catalyzed [4C+3C] Cycloaddition of Allenedienes

et al. 2016

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Abstract:A practical synthesis of (-)-englerin A was accomplished in 17 steps and 11% global yield from commercially available achiral precursors. The key step consists of a Pt-catalyzed [4C+3C] allenediene cycloaddition that directly delivers the trans-fused guaiane skeleton with complete diastereoselectivity. The high enantioselectivity (99% ee) stems from an asymmetric Ru-catalyzed transfer hydrogenation of a readily assembled diene-ynone. The synthesis also features a highly stereoselective oxygenation, and a late-stage cuprate alkylation that enables the preparation of previously inaccessible structural analogues.Along the last years, the guaiane sesquiterpene (−)-englerin A (1, Figure 1) has attracted the attention of chemists, biologists and physicians because of its potent and highly selective activity as inhibitor of renal cancer growth. [1] Recent work carried out independently by Waldmann, Beech and Christmann, [2] as well as by a Novartis' team, [3] identified the transient receptor potential Ca 2+ channel TRPC4 as its main target. [4] TRPC channels are complex membrane proteins that are implicated in multiple biological functions, but they are unusual targets for antitumoral compounds. [5] The activation of this particular channel by 1 has been shown to induce cell death by elevated Ca 2+ influx, [2] however, the general mechanisms that govern TRPC4 activation remains elusive. [5] In this context, the development of efficient and versatile approaches to englerin A and related structural analogues is of major current interest.Since its isolation, [1] several synthesis of englerin have been accomplished, [6,7] some of which are asymmetric. [8] Most of the shortest (<20 steps) asymmetric synthesis rely on the use of prebuilt five-membered rings derived from the chiral pool, and already equipped with key stereocenters of the product. [8b] Although some of these approaches are efficient, the types of analogues that can be assembled are inherently restricted, in particular with respect to the substitution at the five membered ring. [9,10] The groups of Ma and Echavarren independently developed synthetic routes that allow the direct assembly of the bicarbocyclic scaffold of 1 by using a gold-catalyzed cycloisomerization of enantioenriched ketoenynes. [7d,e] The Ma route makes use of the chiral pool to prepare the ketoenyne, whereas Echavarren's approach relies on a Sharpless asymmetric epoxidation to generate the key stereocenter of the annulation precursor. While these approaches are very elegant, the cycloisomerization yields are moderate and the generation of the correct stereochemistry at the ring fusion requires the destruction and regeneration of stereocenters.Herein, we report an enantioselective synthesis of (−)-englerin A that allows to overcome many of the above limitations. The approach relies on a Pt-catalyzed [4C+3C] cycloaddition, and allows to build the bicyclic skeleton of 1 with the correct stereochemistry at the ring fusion, from a readily available allenediene precursor (Figure 1). ...

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“…Among unsaturated substrates involved in these transformations, allenes offered an incomparable versatility since they participate in [2+2], [4+2] or [4+3] cyclizations. 2 In contrast, intermolecular gold-catalyzed cycloadditions with allenes have been less studied. 3 In this sense, significant gold-catalyzed intermolecular [2+2] 4 and [4+2] 5 cycloadditions have been recently reported, 6 including examples of enantioselective versions.…”

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Gold-catalyzed synthesis of tetrahydrocarbazole derivatives through an intermolecular cycloaddition of vinyl indoles and N-allenamides

et al. 2013

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A gold-catalyzed formal [4+2] cycloaddition of vinyl indoles andN-allenamides leading to tetrahydrocarbazoles is described. Moreover, new multicomponent reactions of vinyl indoles with two allene molecules are reported. Besides, tetrahydrocarbazole derivatives are important structures which are key motifs in natural alkaloids and biologically active compounds. 9 Thus, the development of synthetic approaches to this class of compounds constitutes a relevant field of research. Due to our interest in the preparation of functionalized carbazole derivatives 10 and based on the recent work of Mascareñas et al., 5b we decided to study the viability of gold-catalyzed intermolecular cycloadditions of allenes and vinyl indoles, 11 which might offer a simple and selective access to these relevant structures. Herein, we report our findings on selective formal [4+2]-cycloadditions of vinyl indoles and N-allenamides, as well as, gold-catalyzed multicomponent reactions, leading to densely functionalized tetrahydrocarbazoles. Recent developments in homogeneous goldAt the outset, we evaluated the reaction of vinyl indoles with representative allenes. Among various allenes probed, 12 we found that the use of vinyl indoles 1a-b with allenamide 2a gave rise to hydroarylation products 3a-b in moderate yields when using the cationic gold catalyst [Au(PPh 3 )(NTf 2 )]. 13 Assuming that the reaction took place via intermediate I, enhancement of the electrophilicity of the b-carbon on the vinyl moiety might likely facilitate the ring closure. Indeed, when we employed vinyl indole 1c, bearing a carbamate at N-1, under the previous reaction conditions, the desired tetrahydrocarbazole 4a was obtained, along with the unexpected compound 5a (81% combined yield) (Scheme 1). The formation of 5a is remarkable since it resulted from a threecomponent reaction involving two allene molecules. To our knowledge, there are no reports on this transformation in gold catalysis with allenes. Therefore, we searched for selective reaction conditions and evaluated the scope of these transformations.An extensive screening led us to find reaction conditions which enabled a selective access to the desired products (Scheme 2a). 14 Scheme 1 Gold-catalyzed reactions of vinyl indoles 1a-1c with allene 2a: initial findings (isolated yields with respect to 1).

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Ligand-Controlled Access to [4 + 2] and [4 + 3] Cycloadditions in Gold-Catalyzed Reactions of Allene-Dienes

Cited by 232 publications

References 35 publications

Cationic Gold(I)‐Catalyzed Intermolecular [4+2] Cycloaddition between Dienes and Allenyl Ethers

Cationic Gold(I)‐Catalyzed Intermolecular [4+2] Cycloaddition between Dienes and Allenyl Ethers

Concise, Enantioselective, and Versatile Synthesis of (−)‐Englerin A Based on a Platinum‐Catalyzed [4C+3C] Cycloaddition of Allenedienes

Gold-catalyzed synthesis of tetrahydrocarbazole derivatives through an intermolecular cycloaddition of vinyl indoles and N-allenamides

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