Metal-catalyzed cycloisomerization as a powerful tool in the synthesis of complex sesquiterpenoids

Stathakis, Christos I.; Gkizis, Petros; Zografos, Alexandros L.

doi:10.1039/c6np00026f

Cited by 91 publications

(42 citation statements)

References 166 publications

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“…6 The most commonly employed methods include intramolecular aldol reactions, 7 ring-closing metatheses, 8 and metal-catalyzed cycloisomerizations. 9 In addition, ring expansion strategies are well precedented. 10 We envisioned the construction of the cycloheptenone ring of hortonone C to derive from a ring expansion event on known hydrindanone (+)- 4 11 having two out of three required stereocenters already in place.…”

Section: Resultsmentioning

confidence: 99%

A total synthesis of (−)-hortonone C

et al. 2017

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A total synthesis of the cytotoxic terpenoid hortonone C was accomplished and its absolute stereochemistry confirmed. Intermediate (+)-4 was synthesized using either an asymmetric conjugate addition strategy, or by elaboration of the Hajos-Parrish ketone. Reduction of (+)-4 under dissolving-metal conditions and trapping the enolate intermediate served to control the cis-stereochemistry at the ring fusion and provide a silyl enol ether necessary for ring expansion. Comparison of optical rotation data confirmed that the absolute configuration of natural hortonone C is (6S,7S,10S).

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Section: Resultsmentioning

confidence: 99%

A total synthesis of (−)-hortonone C

et al. 2017

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“…Zuschriften oxidant afforded benzo [7,8]indolizino[2,3,4,5-ija]quinolines, the synthesis of which was demonstrated alternatively through alkyne addition and sequential double cyclization. The(Z)-6-alkylidene/benzylidene-6H-isoindolo[2,1-a]indoles could be utilized as effective precursors for various biologically active analogues.T he synthetic scope and applications to material chemistry are currently under investigation.…”

Section: Angewandte Chemiementioning

confidence: 99%

“…[7] Further, cyclo-isomerization is aversatile strategy for creating cyclic organic compounds from acyclic starting materials in an atomeconomical manner. [8] If possible,asimultaneous multiple ring fusion will be highly desirable for more complex molecules.…”

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“…[11] Although there are many examples of regioselective additions,r egiodivergent additions to ynamides or ynamines controlled by transition metals are still elusive.I n the pursuit of af lexible method for the preparation of multifused N-heterocycles,wechose N-alkynylated indoles 1, which are readily prepared under modified reaction conditions, [12] as starting materials,and tested the regioselectivity of intramolecular hydroarylations.H erein, we describe regiodivergent cyclizationsand oxidative cyclodimerization depending on the choice of transition metal and Brønsted acid (Scheme 1). Transition-metal-catalyzed a-a nd b-additiont ovinylogous ynamides (2 and 3), tandem oxidative cyclodimerization (4), alkyne addition (6)a nd TfOH-mediated cycloisomerization (7), and oxidative cyclization (8). In comparison, there have Scheme 1.…”

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confidence: 99%

“…[15] However,i ntramolecular baddition of aryl groups to ynamine is unprecedented to the best of our knowledge [10a] and these cycloisomerizations occurred regardless of the electronic nature of the C2phenyl ring due to the high reactivity of ynamine.I nterestingly,w hen PdCl 2 was used with external oxidant, [16] ac yclodimerized product 4 was obtained. Alternatively,t he synthesis of as imple benzo [7,8]indolizino[2,3,4,5-ija]quinoline 8 was demonstrated through alkyne addition and sequential double cyclization.…”

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Divergent C–H Annulation for Multifused N‐Heterocycles: Regio‐ and Stereospecific Cyclizations of N‐Alkynylindoles

Alam

Hong

et al. 2017

Angewandte Chemie

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N-Alkynylindoles were divergently cyclized for the synthesis of multifused N-heterocycles.A no rtho-aryl palladium species was added to the a position of an ynamine to generate (Z)-6-alkylidene/benzylidene-6H-isoindolo[2,1a]indoles,w hile Pt-catalyzed b-addition through p-activation gave 5-alkyl/arylindolo[2,1-a]isoquinolines.D ouble cyclizations using PdCl 2 and oxidant afforded bright yellow benzo- [7,8]indolizino [2,3,4,5-ija]quinolines,t he synthesis of which was also demonstrated in adifferent synthetic route.

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Palladium‐Catalyzed Cascade Reaction of o‐Bromobenzaldehydes with N‐Sulfonylhydrazones: An Efficient Approach to the Naphthalene Skeleton

et al. 2019

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A new strategy for the construction of the naphthalene backbone is described. The reaction essentially starts from two simple aldehydes. The key step is enabled by a palladium-carbene migratory insertion. After that, a sequence of reversible allylic alkylation and intramolecular condensation takes place to give the substituted naphthalene derivatives. Additional manipulations on the sulfonyl group in the product via palladiumcatalyzed Kumada coupling were also investigated.Cascade reactions are considered as powerful methods to construct structurally complex molecules from simple and readily available feedstocks, while omitting tedious procedures to isolate synthetic intermediates, thus rendering it economic and environmentally benign. [1] Diazo compounds are easily accessible, possessing tunable reactivity. They are often employed as carbene precursors to participate in a range of classical transformations. [2] As demonstrated by the seminal work of van Vranken, Barluenga, Wang, and others, diazo compounds have also proved to be versatile in a variety of transition-metal-catalyzed cross-coupling reactions. [3,4] Recently, we have reported a palladium-catalyzed intermolecular acylation of aryl diazo esters with obromobenzaldehydes, in which diazo esters act as modular three-atom units to build up the key seven-membered palladacycles I (Scheme 1a). [5] To test the synthetic potential of this concept, we envisioned that replacement of carbonyl group with proper CÀC double bond may give a seven-membered carbopalladacyle II, which upon reductive elimination would afford a transient ketone III. Aromatization of III would lead to the formation of final product naphthalen-1-ol (Scheme 1b). In this communication, we would like to describe our efforts toward this goal which leads to an unexpected discovery of a cascade reaction of o-bromobenzaldehydes with a, b-unsaturated N-sulfonylhydrazones enabled by migratory insertion of palladium carbene. This reaction is efficient for the synthesis of a range of naphthyl sulfones and the expected naphthalen-1-ol is not observed (Scheme 1c). Naphthalene unit is an ubiquitous skeleton in chemical and pharmaceutical industries as well as optical and electronic materials. [6] Compared with the existing methods on build up the naphthalene backbone, [7] the current work uses simple aldehydes as the reactants, giving the corresponding substituted naphthalenes in complete regioselectivity with relatively broad substrates scope, thus making this strategy unique and attractive.To begin our study, we chose readily available obromobenzaldehyde 1 a and N-tosylhydrazone 2 a as model substrates. The reaction was initially carried out in DMF at 60 8C for 24 h using Pd 2 dba 3 · CHCl 3 /PPh 3 as the precatalyst, K 2 CO 3 as base (Table 1, entry 1). After careful analysis of the reaction mixture, naphthyl sulfone 3 aa was isolated in 9% yield, and the designed naphthalene-1-ol was not observed. Further inspection of the reaction conditions revealed that COMMUNICATIONS

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Metal-catalyzed cycloisomerization as a powerful tool in the synthesis of complex sesquiterpenoids

Cited by 91 publications

References 166 publications

A total synthesis of (−)-hortonone C

A total synthesis of (−)-hortonone C

Divergent C–H Annulation for Multifused N‐Heterocycles: Regio‐ and Stereospecific Cyclizations of N‐Alkynylindoles

Palladium‐Catalyzed Cascade Reaction of o‐Bromobenzaldehydes with N‐Sulfonylhydrazones: An Efficient Approach to the Naphthalene Skeleton

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