Ring-closing metathesis for the synthesis of benzo-fused bicyclic compounds

Ring-closing metathesis (RCM) was used to synthesise five 4H-chromenes, a naphthol and an indenol. These are the first examples of RCM applied to the synthesis of such benzo-fused bicyclic compounds.     

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.     

Synthesis of enantiomerically pure,highly functionalized,medium-sized carbocycles from carbohydrates: formal total synthesis of (+)-calystegine b(2)

The free radical cyclization (FR) and the ring-closing metathesis (RCM) reaction have been analyzed in order to develop new and original synthetic protocols for the synthesis of enantiomerically pure, highly functionalized, medium-sized carbocycles from carbohydrates. As a result, we report here for the first time examples of the 7-exo FR cyclization of acyclic radical precursors derived from sugars. This process appears to be extremely sensitive to the conformational mobility of the radical species in the transition state. The use of two isopropylidene groups blocking four of the total present hydroxyl groups and a good radical acceptor (as an alpha,beta-unsaturated ester) are mandatory conditions for a successful ring closure protocol. The RCM reaction by using Grubbs' catalyst on selected carbohydrate-derived precursors has afforded variable yields of the expected unsaturated cycloheptane or cycloctane derivatives. The synthesis of the cycloheptitols has been carried out in good yields, regardless of the absolute configuration at the different stereocenters and the nature of the O-functional groups bound in allylic positions to one of the double bonds implicated in the metathesis reaction. Conversely, in the cyclooctane synthesis, we have observed that the success of the reaction depends not only on the absolute configuration at the different stereocenters close to the double bonds but also on the nature of the O-protecting groups on these stereocenters. Finally, the RCM strategy has been used in an attempt to prepare natural (+)-calystegine B(2) from D-glucose. The synthesis of compound 92 from D-glucose constitutes a formal total synthesis of (+)-calystegine B(2), showing the importance of the steric hindrance in allylic positions for a successful RCM reaction.     

New strategy for the total synthesis of macrosphelides a and B based on ring-closing metathesis

[reaction: see text] A new total synthesis of macrosphelides A and B using ring-closing metathesis (RCM) as a macrocyclization step is described. The substrate of the RCM could be synthesized from readily available chiral materials, methyl (S)-(+)-3-hydroxybutyrate and methyl (S)-(-)-lactate, with a high efficiency. The RCM proceeded in the presence of Grubbs' Ru-complex, providing a new effective synthetic route to these natural products.     

关环转换反应在天然产物合成中的应用

关环转换反应是形成碳碳双键的重要反应之一,即双烯化合物在金属碳烯催化下关环得到环烯类化合物。本文概述了关环转换反应所用催化剂体系及其在天然产物合成中的应用,内容涉及到碳环及含氧、含氮杂环天然产物的合成。     

关环复分解反应(RCM)及其催化剂研究进展

综述了近年来关环复分解 (RCM )反应及其催化剂的研究进展 ,对RCM反应发展以来被广泛应用的催化剂 ,如Schrock催化剂和Grubbs催化剂等进行了归纳和总结 ,讨论了RCM反应在全合成中的应用     

Stereoselective Synthesis of 2-(2-Hydroxyalkyl)piperidine Alkaloids Through Prins–Ritter Reaction

A stereoselective total synthesis of the 2-(2-hydroxyalkyl)piperidine alkaloids has been accomplished by a Prins–Ritter amidation sequence. Other steps involved in this synthesis are Jacobsen's hydrolytic kinetic resolution (HRK) and ring-closing metathesis (RCM).     

Total synthesis of (-)-nakadomarin A

A highly diastereoselective bifunctional organocatalyst controlled Michael addition, a nitro-Mannich/lactamization cascade, a furan N-acyliminium cyclisation, a sequential alkyne RCM/syn-reduction and an alkene RCM has allowed a 19 step, highly stereoselective synthesis of (-)-nakadomarin A.     

Synthesis of 2-phosphonopyrroles via a one-pot RCM/oxidation sequence

A four-step synthesis of 2-phosphonopyrroles is presented starting from suitable aldehydes. The key step in the synthesis involves a one-pot ring-closing metathesis/oxidation sequence of a functionalized alpha-aminoalkenyl phosphonate. Notwithstanding the presence of a nucleophilic nitrogen atom and high substitution patterns in the substrate, the results of the RCM reaction are excellent using mild reaction conditions. Furthermore, a synergism is observed between the RCM catalyst and the oxidizing agent, causing higher oxidation rates and allowing reaction for substrates that normally fail to ring close under standard RCM conditions.     

Synthesis of cyclic peptides by ring-closing metathesis

The synthesis of a series of "amide to amide" cyclized peptides by ring-closing metathesis (RCM) as well as a convenient synthesis for the linear precursors is described. In addition, the influence of the length of the alkene substituents and the influence of the peptide sequence is investigated, leading to a set of general rules to obtain "amide to amide" cyclized peptides by RCM.     

New approaches to the synthesis of organofluorine nitrogenated derivatives

Fluorinated carboxylic acids are valuable building blocks for several types of organofluorine nitrogenated derivatives. In this review paper, several strategies that use these compounds as starting materials are described. First, fluorinated seven-membered cyclic β-amino esters can be diastereoselectively synthesized from these compounds with a ring-closing metathesis (RCM) reaction as the key step. The use of the RCM reaction in a different approach enables the preparation of fluorinated cyclic α-amino acid derivatives. Fluorinated carboxylic acids also constitute the starting material for the asymmetric synthesis of fluorinated allylic amines. Finally, a solution and solid-phase synthesis of fluorinated uracils and thiouracils is described.     

Formal total synthesis of (+)-salicylihalamides A and B: a combined chiral pool and RCM strategy

The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral pool approach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for the formation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, the formal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It was found that substitution at the remote phenolic group significantly influenced the ratio of the E- and Z-double bond products in the RCM step. The introduction of phenol protecting groups provided E-isomers preferentially and also enhanced the rates of the RCM reactions.     

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.     

Formal synthesis of optically active ingenol via ring-closing olefin metathesis

The construction of strained carbon skeletons by ring-closing olefin metathesis (RCM) was investigated. With well-designed diene 4, RCM was found to be applicable to the formation of a highly strained inside-outside bicyclo[4.4.1]undecane skeleton of ingenol, a bioactive diterpenoid, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of the ketone with an allylic chloride unit, 26, and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 6, the key intermediate aldehyde 9 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.     

Construction of carbocyclic ring of indoles using ruthenium-catalyzed ring-closing olefin metathesis

The selective synthesis of substituted indoles was achieved by the ring-closing olefin metathesis (RCM)/elimination sequence or the RCM/tautomerization sequence of functionalized pyrrole precursors. The RCM/elimination sequence was also applied to double ring closure to yield a substituted carbazole.     

Ring-closing metathesis as a basis for the construction of aromatic compounds

The use of metathesis, especially in the context of ring-closing metathesis (RCM) to form five- and six-membered rings, is widespread in organic chemistry today. However, there are surprisingly few examples of the reaction being used to form aromatic compounds. The central place of aromatic compounds in both medicinal chemistry and natural products synthesis, coupled with the efficiency and functional group tolerance of RCM catalysts, means that there is now an interesting opportunity to use RCM for the synthesis of arenes. Although the formation of an aromatic compound was viewed in many early examples as an undesirable degradation product, several rationally designed methods towards the preparation of aromatic compounds by RCM have recently been developed.     

Kinetically controlled ring-closing metathesis: synthesis of a potential scaffold for 12-membered salicylic macrolides

For the synthesis of a 12-membered salicylic macrolide scaffold, ring-closing metathesis (RCM) of a omega-diene compound was planned. The stereochemical outcome of the RCM reaction changed depending on the type of Ru catalyst that was used; a "first-generation" Grubbs catalyst produced exclusively the E isomer and "second-generation" catalysts provided a mixture of the E and Z isomers under kinetic control (not thermodynamic control). Considerations for the E/Z selectivity are described.     

A ketal-tethered RCM strategy toward the synthesis of spiroketal related natural products

An unconventional approach to construct spiroketals and spiroaminals via ring-closing metathesis [RCM] of cyclic ketals and aminals, respectively, is described here. This method possesses a good generality with no loss of stereochemical integrity at the spirocenter under the standard RCM conditions. This approach has been applied to the synthesis of an insect pheromone to demonstrate its synthetic potential, and also to the synthesis of the C11-epi-C22-C23 fragment in spirastrellolide A. Both are proof-of-concept applications to feature a ketal-tethered RCM as an alternative strategy for construction of spiroketals.     

A facile synthetic route to (+)-allosedamine via hydrolytic kinetic resolution and olefin metathesis

A concise synthesis of (+)-allosedamine has been achieved using cobalt-catalyzed hydrolytic kinetic resolution (HKR) and ruthenium-catalyzed ring closing metathesis (RCM) as two key steps, in which HKR was used to introduce both stereogenic centers in the natural compound with a high degree of diastereomeric ratio and cyclization was carried out with the well developed RCM procedure.