Stereoselective synthesis of (+)-diplodialides-B,C and a formal synthesis of (+)-diplodialide-A by ring-closing metathesis approach

Stereoselective synthesis of diplodialides-B and C and the formal synthesis of diplodialide-A are reported. A combination of Jacobsen’s hydrolytic kinetic resolution and Sharpless epoxidation is used for the creation of two stereogenic centers, while a ring-closing metathesis strategy was used for the construction of the lactone ring.     

Stereoselective synthesis of the phorboxazole A macrolide by ring-closing metathesis

[Structure: see text] Described is a regio- and stereoselective ring-closing metathesis (RCM) to form the C2-C3 alkene of the macrolide-containing domain of phorboxazole A. This work demonstrates a dramatic effect of reaction solvent on RCM product (E/Z)-selectivity. This process offers an alternative assembly of the macrolide-containing domain of phorboxazole A, one of the most potent anticancer agents known.     

Carbohydrate carbocyclization by a zinc-mediated tandem reaction and ring-closing enyne metathesis

Methyl 5-deoxy-5-iodo-pentofuranosides are reductively ring-opened and propargylated in a tandem fashion in the presence of zinc. The 1,7-enynes thus obtained are subjected to ring-closing enyne metathesis with catalyst B to produce functionalized 1-vinyl cyclohexenes. By adding BnNH(2) to the tandem reaction, an amino group can be introduced in the 1,7-enyne products. Addition of 2-TMS-ethynylcerium(III) chloride after the reductive ring-opening produces the corresponding 1,6-enynes. Further annulation of the product 1,3-dienes can be achieved through a Diels-Alder reaction with good control of stereochemistry. These procedures constitute efficient methods for rapid carbocyclization and annulation of carbohydrates to produce a variety of functionalized five- and six-membered ring systems.     

Stereoselective synthesis of (−)-malyngolide, (+)-malyngolide and (+)-tanikolide using ring-closing metathesis

The stereoselective syntheses of the naturally occurring δ-lactones (+)-tanikolide and (−)-malyngolide as well as of the unnatural (+)-enantiomer of the latter are described. Key steps in each of these syntheses were stereoselective additions of organometallic reagents to α-oxygenated ketones and olefin ring-closing metatheses.     

Application of tandem Ugi reaction/ring-closing metathesis in multicomponent synthesis of unsaturated nine-membered lactams

A new straightforward entry into unsaturated nine-membered lactams of potential use as external reverse turn inducers was developed. It is based on an Ugi multicomponent reaction using two unsaturated substrates, followed by highly stereoselective ring-closing metathesis (RCM). The synthesis of a nine-membered secondary lactam by RCM is reported for the first time.     

Total synthesis of (+)-phomopsolide C by ring-size selective ring-closing metathesis/cross-metathesis

[reaction: see text]A new strategy for the synthesis of chiral 6-substituted 5,6-dihydro-5-hydroxypyran-2-ones by ring-size selective ring-closing metathesis (RCM) and its application to a short total synthesis of (+)-phomopsolide C are described. The key bond-forming reactions in this approach are a chemoselective cross-metathesis (CM) and RCM.     

Stereoselective synthesis of cis- and trans-2,3-disubstituted eight-membered medium-ring ethers based on Ireland-Claisen rearrangement of 3-alkoxy-2-propenyl glycolate esters and ring-closing olefin metathesis

A simple stereoselective synthesis of cis- and trans-2,3-disubstituted medium-sized cyclic ethers has been developed based on geometry-selective synthesis of 3-alkoxy-2-propenyl glycolate esters, Ireland-Claisen rearrangement of the glycolate esters, and ring-closing olefin metathesis.     

Concise total synthesis of (-)-muricatacin by tandem ring-closing/cross metathesis

A strategy for the synthesis of chiral 5-(1-hydroxyalk-2-enyl)-5H-furan-2-ones and its application to the total synthesis of (-)-muricatacin, in four steps and 37% overall yield from (R,R)-hexa-1,5-diene-3,4-diol, are described. The key synthetic step in this approach is a highly regioselective and stereoselective tandem ring-closing/cross metathesis reaction in which both lactone formation and alkyl chain extension are accomplished in an efficient one-pot process.     

Enantioselective synthesis of cyclic enol ethers and all-carbon quaternary stereogenic centers through catalytic asymmetric ring-closing metathesis

The first examples of catalytic asymmetric ring-closing metathesis (ARCM) reactions of enol ethers are reported. To identify the most effective catalysts, various chiral Mo- and Ru-based catalysts were screened. Although chiral Ru catalysts (those that do not bear a phosphine ligand) promote ARCM in some cases, such transformations proceed in <10% ee. In contrast, Mo-based alkylidenes give rise to efficient ARCM and deliver the desired products in the optically enriched form. Thus, Mo-catalyzed enantioselective transformations allow access to various five- and six-membered cyclic enol ethers in up to 94% ee from readily available achiral starting materials. The first examples of catalytic ARCM that lead to the formation of all-carbon quaternary stereogenic centers are also disclosed. Mechanistic models that offer a plausible rationale for the identity of major enantiomers as well as the observed levels of enantioselectivity are provided. Representative examples demonstrate that the enol ether moiety and the unreacted alkene of the ARCM products can be discriminated with excellent site selectivity (>98%).     

Regioselectivity in the formation of small- and medium-sized cyclic ethers by diene-ene ring-closing metathesis

In the formation of medium-sized ethers by diene-ene ring-closing metathesis, the formation of cyclic allyl ethers with a smaller ring size and of pentadienyl ethers with a larger ring size compete with each other. In the competition between six- and eight-membered and seven- and nine-membered ring formation, the smaller rings are formed exclusively, whereas in the competition between the five- and seven-membered rings, both products are formed in comparable amounts.     

Synthesis of cyclic sulfones by ring-closing metathesis

A general and highly efficient synthesis of cyclic sulfones based on ring-closing metathesis has been developed. The synthetic utility of the resulting cyclic sulfones was demonstrated by their participation in stereoselective Diels-Alder reactions and transformation to cyclic dienes by the Ramberg-B?cklund reaction.     

Synthesis of cyclic peptidosulfonamides by ring-closing metathesis

N-Protected beta-aminoethanesulfonyl chlorides (2a-e) were used in the preparation of sulfonamides 4, 8, 11a-c, and 15. Ring-closing metathesis of sulfonamides 4 and 8 did not lead to the expected nine-membered cyclic peptidosulfonamides. In contrast, the allylated peptidosulfonamides 11a-c and 15 turned out to be suitable precursor systems for ring-closing metathesis using second-generation Grubbs catalyst and nine-membered cyclic peptidosulfonamides were obtained in 47-60% yields. The possibility for incorporation of these cyclic peptidosulfonamides into a peptide sequence was illustrated by the incorporation of an amino acid on the "S"- or "N"-terminus leading to 16 and 18-20, respectively. A model of cyclic peptidosulfonamide 16 hints at an extended-like structure.     

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.     

Selective construction of carbocyclic eight-membered rings by ring-closing metathesis of acyclic precursors

Although the efficient preparation of cyclooctanoids has remained a long-standing objective, a real breakthrough was possible only relatively recently with the development of more specific reagents and by the development of new reactions. The direct construction of carbocyclic eight-membered rings from acyclic precursors is still a challenge, mainly because of unfavorable entropic and enthalpic factors that preclude ring formation. This Minireview describes the utilization of ring-closing metathesis (RCM) as a new approach to synthesize cyclooctanoids.     

Formal synthesis of (+/-)-guanacastepene A: a tandem ring-closing metathesis approach

A concise route to a key intermediate in the total synthesis of guanacastepene A is described. The main features include the simultaneous construction of the seven- and six-membered rings, using a tandem ring-closing metathesis and a stereoselective introduction of the oxygenated function at the C5 position. [reaction: see text]     

Selective formation of dihydropyran derivatives by a tandem domino ring-closing metathesis/cross-metathesis

A ring-closing metathesis (RCM)/cross-metathesis (CM) domino reaction has been applied to esters and unsymmetrical ether prepared from 1,5-hexadien-3-ol. For the first time, dihydropyran derivatives have been obtained via a regioselective cyclization. This reaction was performed in high yield and E stereoselectivity.     

Total synthesis of cyclic diterpene tonantzitlolone based on a highly stereoselective substrate-controlled aldol reaction and ring-closing metathesis

The total synthesis of the cyclic diterpene ent-tonantzitlolone (ent-1) is presented. Key steps for assembling the macrocyclic core structure of 1 are a highly selective aldol reaction and an E selective ring-closing metathesis reaction. A detailed investigation of these two steps and the final transformations towards the completion of the synthesis is disclosed.     

An efficient synthesis of nitrogen-containing heterocycles via a tandem carbenoid N-H insertion/ring-closing metathesis sequence

A series of five- to eight-membered nitrogen-containing heterocycles were prepared via a general and efficient one-pot, two-component sequence featuring rhodium-catalyzed insertion of a vinyl-substituted α-diazocarbonyls into the N-H bond of a series of tert-butoxycarbonyl-(Boc)-protected amines, followed by ring-closing metathesis catalyzed by ruthenium benzylidene complexes. This methodology allows easy and convenient access to highly functionalized azacycloalkenes in moderate yields and excellent chemoselectivity in a single transformation.     

Stereoselective synthesis of myo-inositol via ring-closing metathesis: a building block for glycosylphosphatidylinositol (GPI) anchor synthesis

Here we report a concise stereoselective synthesis of myo-inositol via ring-closing metathesis. A readily available bis-Weinreb amide of D-tartrate served as a key intermediate. [reaction: see text]