Tandem Ring‐Opening–Ring‐Closing Metathesis for Functional Metathesis Catalysts

Use of a tandem ring‐opening–ring‐closing metathesis (RORCM) strategy for the synthesis of functional metathesis catalysts is reported. Ring opening of 7‐substituted norbornenes and subsequent ring‐closing metathesis forming a thermodynamically stable 6‐membered ring lead to a very efficient synthesis of new catalysts from commercially available Grubbs’ catalysts. Hydroxy functionalized Grubbs’ first‐ as well as third‐generation catalysts have been synthesized. Mechanistic studies have been performed to elucidate the order of attack of the olefinic bonds. This strategy was also used to synthesize the ruthenium methylidene complex.     

Total synthesis of (+/-)-asteriscanolide.

The total synthesis of asteriscanolide (1) has been achieved by taking advantage on an intermolecular Pauson-Khand cycloaddition and a ring-closing metathesis as key bond-forming transformations. The approach incorporates the cyclooctane stereogenic center prior to ring formation. Interestingly, the ring-closing metathesis generates a new eight-membered ring with an "in-out" intrabridgehead relationship.     

Variable and stereoselective synthesis of azasugar analogues by a ruthenium-catalyzed ring rearrangement

A novel ruthenium-catalyzed ring opening/ring closing tandem metathesis reaction with a catalytic transfer of stereocenters from a ring to an olefinic chain is described. This ring rearrangement serves as the key step in the stereoselective synthesis of the new azasugar analogues 1 and 2.     

Synthesis of a [2]catenane around a Ru(diimine)3(2+) scaffold by ring-closing metathesis of olefins

[reaction: see text] The synthesis of a ruthenium[2]catenane is described. One ring includes two 1,10-phenanthroline moieties, the other a bipyridinic unit. The interlocking ring system was formed by using a double ring closing metathesis reaction. Under irradiation, a rapid and selective decoordination of the bipyridinic fragment was observed, leading to a new catenane in which the metal is only coordinated to the bis-phenanthroline moiety.     

Concise enantioselective synthesis of (−)-lasubine II

An enantioselective synthesis of the quinolizidine alkaloid (−)-lasubine II 1 is reported. Two different pathways to the key intermediate 2 are described. The first case involving a sequence of ring rearrangement metathesis (RRM), simple functional group interconversion operations, followed by a stereoselective cross metathesis (CM) and in the second case a domino ring opening-/ring closing-/cross metathesis step is involved. In both cases, following the metathesis reactions, exclusively the E-isomer was obtained. The final cyclisation towards the quinolizidine skeleton is achieved by an intramolecular Michael reaction. This concept represents the first example of a highly stereoselective RRM-CM combination in the synthesis of a natural product.     

Synthesis of Substituted Indenes from Isovanillin via Claisen Rearrangement and Ring‐Closing Metathesis

A new synthesis of substituted indenes was studied. Based on Claisen rearrangement, Wittig reaction and ring‐closing metathesis (RCM), a series of substituted indenes was synthesized from isovanillin in good yields.     

Ring closing enyne metathesis: a powerful tool for the synthesis of heterocycles

The ring closing metathesis (RCM) is a powerful method in organic synthesis for the preparation of cyclic compounds by formation of new carbon-carbon bonds. In the past years a particular subclass of the RCM, the ring closing enyne metathesis (RCEYM), has attracted attention due to its synthetic potential in the generation of ring structures with 1,3-diene moieties, which can subsequently be further functionalised. In this tutorial review mechanistic considerations will be described and the synthetic power of this useful and attractive carbon-carbon bond forming reaction will be illustrated by recent examples of RCEYM applications in the preparation of heterocyclic compounds.     

A Straightforward Approach towards Cyclic Photoactivatable Tubulysin Derivatives

The development of a new photolabile protecting group containing an additional allyl functionality allows the synthesis of cyclic photoactivatable natural products. Cyclization occurs between the allyl moiety in the protecting group and a second double bond in the target molecule by means of ring‐closing metathesis. Cyclization should increase the metabolic stability towards proteases. On the other hand, the conformational change should cause diminished biological activity. As illustrated for tubulysin derivatives, cyclic and photoactivatable drug candidates can easily be obtained in only two steps from simple building blocks through Ugi reaction and ring‐closing metathesis. The photolabile protecting group is introduced by means of the isocyanide component during the Ugi reaction.     

Synthesis of phosphorus containing medium ring heterocycles by sequential Claisen rearrangement and ring closing metathesis

An efficient method for the synthesis of novel medium ring phosphorus containing heterocycles starting from phenol derivatives by ruthenium catalyzed ring closing metathesis is described. This work deals with a sequential aromatic Claisen-rearrangement, coupling of an allyl/vinyl phosphonate, and ring closing metathesis reaction. All of these reactions were carried out at ambient temperature to afford the medium-sized phosphorus heterocycles in excellent yields.     

过渡金属催化的6-苯基-5,6-二氢-2H-吡喃-2-酮的合成——推荐一个大学有机化学综合实验

有机合成中,碳-碳键的形成和断裂是一个永恒的热门话题,科学家为此发展了很多形成碳-碳键的方法。在这一领域,诞生了不少诺贝尔化学奖的成果,格氏反应和烯烃复分解反应就是其中的经典案例。烯烃复分解反应提供了一种连接sp2-碳和sp2-碳的全新思路,发展出了一些活性分子全合成的高效路径。因而,2005年的诺贝尔化学奖授予了对烯烃复分解反应有杰出贡献的三位科学家。本有机化学综合实验由三个反应构成,包括改进的格氏反应、DMAP催化的酯化反应和关环烯烃复分解反应。每一个反应都可独立成为一个基础有机化学实验,三步的连续反应可以作为一个综合多步合成实验。本实验有助于理解有机合成的过程和机理,体验有机合成的魅力。     

Enantioselective Total Synthesis of Terreumols A and C from the Mushroom Tricholoma terreum

The cytotoxic meroterpenoids terreumol A and C from the grey knight mushroom Tricholoma terreum were synthesized for the first time. The key step of the enantioselective total synthesis of terreumol C is a ring‐closing metathesis to form a trisubstituted Z double bond embedded in the 10‐membered ring of the [8.4.0] bicycle. Interestingly, the presence of a free hydroxy group in the metathesis precursor prevents cyclization and favors cross metathesis. (?)‐Terreumol C was converted into (?)‐terreumol A by diastereoselective epoxidation. Starting from 2‐bromo‐3,5‐dimethoxybenzaldehyde, 14 steps with an overall yield of 23 % are needed for the synthesis of (?)‐terreumol A. X‐ray analysis of the benzoquinone analogue of terreumol A provides independent proof of the absolute configuration.     

FeCl3‐Catalyzed Ring‐Closing Carbonyl–Olefin Metathesis

Exploiting catalytic carbonyl–olefin metathesis is an ongoing challenge in organic synthesis. Reported herein is an FeCl₃‐catalyzed ring‐closing carbonyl–olefin metathesis. The protocol allows access to a range of carbo‐/heterocyclic alkenes with good efficiency and excellent trans diastereoselectivity. The methodology presents one of the rare examples of catalytic ring‐closing carbonyl–olefin metathesis. This process is proposed to take place by FeCl₃‐catalyzed oxetane formation followed by retro‐ring‐opening to deliver metathesis products.     

Targeting the Hsp90 Chaperone: Synthesis of Novel Resorcylic Acid Macrolactone Inhibitors of Hsp90

A series of benzo‐macrolactones has been prepared by chemical synthesis, and evaluated as inhibitors of heat shock protein 90 (Hsp90), an emerging attractive target for novel cancer therapeutic agents. A new synthesis of these resorcylic acid macrolactone analogues of the natural product radicicol is described in which the key steps are the acylation and ring opening of a homophthalic anhydride to give an isocoumarin, followed by a ring‐closing metathesis to form the macrocycle. The methodology has been extended to a novel series of macrolactones incorporating a 1,2,3‐triazole ring.     

Ring synthesis by stereoselective, methylene-free enyne cross metathesis

Tandem enyne metathesis between 1-alkynes and 1,5-cyclooctadiene or all-cis-1,4-polybutadiene resulted in a direct, one-step ring synthesis of cyclohexadienes by methylene-free metathesis. The use of methylene-free metathesis conditions provided apparent Z-selectivity in the intermolecular enyne metathesis step.     

Total Synthesis of the Isodon Diterpene Sculponeatin N

The total synthesis of sculponeatin N, a bioactive polycyclic diterpene isolated from Isodon sculponeatus, is reported. Key features of the synthesis include diastereoselective Nazarov and ring‐closing metathesis reactions, and a highly efficient formation of the bicyclo[3.2.1]octane ring system by a reductive radical cyclization.     

Synthesis of pyranonaphthoquinone antibiotics involving the ring closing metathesis of a vinyl ether

The synthesis of two antibiotic pyranonaphthoquinones was performed by a straightforward synthetic route utilizing ring closing metathesis. Vinylation of 3-(1-propenyl)-2-hydroxymethyl-1,4-dimethoxynaphthalene under iridium catalysis and subsequent ring closing metathesis of 3-(1-propenyl)-2-vinyloxymethyl-1,4-dimethoxynaphthalene with Grubbs' catalyst paved the way to the natural antibiotics pentalongin and psychorubrin.     

A Thermo‐ and Photo‐Switchable Ruthenium Initiator For Olefin Metathesis

A ruthenium carbene complex bearing azobenzene functionality is reported. The complex exists in the form of two isomers differing by the size of the chelate ring. Both isomers were isolated by applying kinetic or thermodynamic control during the synthesis and characterized by X‐ray diffraction analysis. The isomerization of the complex was studied by UV/Vis spectroscopy. The stable isomer was tested as a catalyst in olefin metathesis. The complex was activated at about 100 °C to promote ring‐closing and ring‐opening polymerization metathesis reactions. The activation took place also at room temperature under middle ultraviolet radiation.     

An efficient total synthesis of 9-methoxycarbazole-3-carbaldehyde based on a novel methodology for the preparation of methoxyindoles

A direct synthesis of naturally occurring 9-methoxycarbazole-3-carbaldehyde 1, based on our methodology for the synthesis of 1-methoxyindoles, is reported. A novel benzannulation strategy was employed using ring closing metathesis as the key step in this total synthesis. The synthesis of the natural product 1 has been achieved in seven steps in 14% overall yield from commercial materials and in only four steps from a methoxyindole compound obtained using the new methodology.     

Stereoselective synthesis and structural correction of the naturally occurring lactone stagonolide G

A convergent synthesis of the structure proposed for the naturally occurring lactone stagonolide G is described. All three stereocenters were created with the aid of asymmetric Brown allylations. The lactone ring was built by means of a ring-closing metathesis (RCM). The synthetic and the natural compound differed in their spectral properties. A new structure is now proposed for stagonolide G and demonstrated by means of a chemical transformation.