Unprecedented Selectivity of Ruthenium Iodide Benzylidenes in Olefin Metathesis Reactions

The development of selective olefin metathesis catalysts is crucial to achieving new synthetic pathways. Herein, we show that cis‐diiodo/sulfur‐chelated ruthenium benzylidenes do not react with strained cycloalkenes and internal olefins, but can effectively catalyze metathesis reactions of terminal dienes. Surprisingly, internal olefins may partake in olefin metathesis reactions once the ruthenium methylidene intermediate has been generated. This unexpected behavior allows the facile formation of strained cis‐cyclooctene by the RCM reaction of 1,9‐undecadiene. Moreover, cis‐1,4‐polybutadiene may be transformed into small cyclic molecules, including its smallest precursor, 1,5‐cyclooctadiene, by the use of this novel sequence. Norbornenes, including the reactive dicyclopentadiene (DCPD), remain unscathed even in the presence of terminal olefin substrates as they are too bulky to approach the diiodo ruthenium methylidene. The experimental results are accompanied by thorough DFT calculations.     

Enantioselective synthesis of chromenes

A concise approach for the synthesis of optically active chromenes is reported. The process described herein involves, as the key steps, a Sharpless-epoxidation, a selective deoxygenation, and a ring-closing metathesis.     

Claisen rearrangement/Baylis-Hillman reaction/ring-closing metathesis as bases for the construction of substituted cyanonaphthalenes

The present paper described how to establish a novel approach for various alkoxycyanonaphthalenes. It was started from isovanillin, and based on the Claisen rearrangement, O-alkylation, the Baylis-Hillman reaction, and ring-closing metathesis in sequence to produce the title compounds in good yield.     

Assessing synthetic strategies: total syntheses of (+/-)-neodolabellane-type diterpenoids

Two strategies, namely a cross-metathesis/ring-closing metathesis and Pd-catalyzed Stille allylation/Nozaki-Hiyama-Kishi coupling, are examined for the preparation of neodolabellane-type diterpenoids 1 and 2. Whereas the first approach possessed synthetic limitations, the latter was successfully employed to provide compounds 1 and 2 in 8.8% (14 steps) and 8% (15 steps) overall yields, respectively.     

Microwave-assisted multi-step synthesis of novel pyrrolo-[3,2-c]quinoline derivatives

A new approach for the synthesis of original substituted pyrrolo-[3,2-c]quinoline derivatives using microwave-assisted chemistry is described. The use of microwave activation in this synthesis resulted in high yielding and clean steps. The key step for introducing diversity is the amination or the Pd-catalyzed cross-coupling of an imidoyl chloride derivative, obtained in a straightforward manner and in good yield.     

The tandem ring-closing metathesis-isomerization approach to 6-deoxyglycals

Protected 3,6-dideoxyglycals have been synthesized de novo as single isomers starting from ethyl lactate by using the tandem RCM-isomerization reaction as the key step. Different relative configurations become accessible by addition of vinyl- or allyl-metal compounds to protected lactaldehydes under Cram-chelate or Felkin-Anh control. The concept is exemplified for glycals of L-rhodinose and L-amicetose, as well as for ring-expanded non-natural analogues thereof. This novel approach to glycals is also applicable to the synthesis of disaccharide glycals via a reiterative strategy, as exemplified for the dimer of L-rhodinose and its non-natural ring expanded analogue.     

Studies Toward Synthesis of Tetracyclic Core of Daphmanidin A–Type Alkaloids

A stereoselective approach to spiro-annulated bicyclo[2.2.2]octane ring system related to the tetracyclic skeleton of daphmanidin A–type alkaloids is described. Ring-closing metathesis, Wacker oxidation, and aldol condensation are key features ofour approach. An interesting steric effect on aldol condensation has also been observed.     

Synthesis of the floresolide B hydroquinone lactone core using ring-closing metathesis

The hydroquinone lactone core of the floresolides was synthesized through a ring-closing metathesis (RCM) approach. Optimal RCM efficiency was obtained at higher reaction concentration. An unexpected Lewis acid-promoted rearrangement of the hydroquinone and other observations relevant to on-going total synthesis efforts are discussed.     

Simple Synthesis of Versatile Coumarin Scaffolds

We describe an approach using ring‐closing metathesis (RCM) to synthesize versatile coumarin derivatives that present appropriate substitutions both at the aromatic and at the α,β‐unsaturated lactone ring. The obtained compounds can be used as molecular scaffolds suitable for further diversifications through a combinatorial approach.     

Application of an isomerization-ring-closing metathesis strategy to the synthesis of unsaturated seven-membered, benzo-fused heterocycles containing two heteroatoms

An isomerization-RCM approach was utilized to synthesize a number of seven-membered benzo-fused heterocycles containing two heteroatoms (N,O, N,S, and S,O). This approach utilized the ruthenium catalyst [RuClH(CO)(PPh₃)₃] for the isomerization of allyl groups, eventually followed by the use of the Grubbs second generation catalyst for the formation of the desired products. In most instances thermal RCM conditions were sufficient; however, in a number of cases where this methodology did not give the desired product a high temperature, short time microwave approach afforded the desired ring-closed products. In this manner, the following substituted benzo-fused scaffolds were successfully synthesized: 4,5-dihydro-1,5-benzoxazepine, 4,5- and 2,5-dihydro-1,5-benzothiazepine and 2H-1,5-benzoxathiepine.     

Dienyne ring-closing metathesis approach for the construction of taxosteroids

A cascade dienyne ring-closing metathesis approach has been applied to the synthesis of the tetracyclic carbon framework of a new class of hybrid compounds-the taxosteroids-possessing carbon frameworks incorporating moieties characteristic of both taxanes (such as AB rings) and steroids (i.e., CD system and side chain). This tandem cyclization is highly stereoselective, allowing the one-step formation of the bicyclo[5.3.1]undecene system characteristic of taxol. In this work we describe the scope and limitations of such cyclizations.     

Total Synthesis of Resorcylic Acid Lactone (−)-Neocosmosin A Using Palladium-Catalyzed α-Arylation of Enones as the Key Step

The total synthesis of the 14-membered resorcylic acid lactone neocosmosin A is described. The key step in the synthesis is the palladium-catalyzed α-arylation of TES-enol ethers of enones. The employment of the α-arylation approach to this class of resorcylic acid lactones is a new approach, which has the scope of being generalized into a unified approach for the synthesis of this class of natural products.     

Diversity-oriented approach to biologically relevant molecular frameworks starting with beta-naphthol and using the Claisen rearrangement and olefin metathesis as key steps

A diversity-oriented approach for the synthesis of various structurally different molecular frameworks from readily accessible and common precursors is described. A Claisen rearrangement followed by ring-closing metathesis or ethylene-promoted ring-closing enyne metathesis has been utilized as the key synthetic transformation to generate naphthoxepine derivatives. The ring-closing metathesis approach has also been used to generate spirocyclic compounds and the pleiadene framework.     

Stereodivergent Synthesis of Piperidine Alkaloids by Ring‐Rearrangement Metathesis/Reductive Lactam Alkylation of Nitroso Diels–Alder Cycloadducts

A general methodology for the stereoselective synthesis of 2‐(2‐hydroxyalkyl)piperidine alkaloids by ring‐rearrangement metathesis of nitroso Diels–Alder cycloadducts is reported. The approach is illustrated by the formal synthesis of porantheridine and the total synthesis of andrachcinidine through a diastereodivergent allylation of an N‐alkoxy bicyclic lactam. The asymmetric synthesis of the latter alkaloid provides new insights into the configurational stability of cycloadducts between chloronitroso reagents and cyclopentadiene.     

Total synthesis of patulolide A through ring closing metathesis

A simple and efficient total synthesis of patulolide A from readily available 7-octen-1-ol is reported by asymmetric synthetic approach. The key reactions involved are asymmetric dihydroxylation using AD-mix-β and Grubbs’ ring-closing metathesis reaction for the synthesis macrocyclic ring system.     

Ring-rearrangement metathesis of 3,6-dialkoxy-3,6-dihydro-2H-pyrans

The first RCM-ROM-RCM sequence using a non-strained heterocycle as relay moiety is described. The course of the reaction strongly depends on the nature and relative configuration of the substituents in the starting trienic system. In addition, for a productive reaction to be observed, the site of initiation of the metathesis cascade is crucial. The compounds thus obtained may be useful for the synthesis of unusual polydeoxydisaccharides.     

Studies toward Taxuspine X, a potent multidrug-resistance reversing agent, via ring closing metathesis strategy

The synthesis of bicyclic 3,8-secotaxane diterpenoids, which includes Taxuspine U and X, has been achieved through an approach that involves a ring closing metathesis reaction as key step for the macrocycle formation.     

Surface‐Functionalized Nanoparticles by Olefin Metathesis: A Chemoselective Approach for In Vivo Characterization of Atherosclerosis Plaque

The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well‐defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanoparticles with three different examples. This approach enables, in one step, the synthesis and functionalization of different water‐stable magnetite‐based particles from oleic acid‐coated counterparts. The surface of the nanoparticles was completely characterized showing how the metathesis approach introduces a large number of hydrophilic molecules on their coating layer. As an example of the possible applications of these new nanocomposites, a focus was taken on atherosclerosis plaques. It is also demonstrated how the in vitro properties of one of the probes, particularly its Ca²⁺‐binding properties, mediate their final in vivo use; that is, the selective accumulation in atherosclerotic plaques. This opens promising new applications to detect possible microcalcifications associated with plaque vulnerability. The accumulation of the new imaging tracers is demonstrated by in vivo magnetic resonance imaging of carotids and aorta in the ApoE^?/? mouse model and the results were confirmed by histology.     

Carbohydrate-based oxepines: ring expanded glycals for the synthesis of septanose saccharides

A ring-closing metathesis (RCM) approach to a family of carbohydrate-based oxepines is described. A variety of readily accessible, protected monosaccharide derived dienes were used to demonstrate the utility of the synthetic sequence and to investigate how factors such as rigidification and deoxygenation mediate RCM using the Grubbs or Schrock catalyst. The seven-membered cyclic enol ethers are ring expanded glycals to be used in the synthesis of septanose carbohydrates.     

A concise and enantioselective approach to the total synthesis of (−)-lasubine I

An efficient, enantioselective total synthesis of (−)-lasubine I (1) has been achieved in an overall 8.8% yield from readily available starting materials. The important features of this approach include the creation of stereogenic centers through two sequential highly stereoselective Roush allylborations and the use of S_N2 cyclization and ring-closing metathesis reactions for the construction of the quinolizidine skeleton.