Janine Cossy

Metathesis in natural product synthesis : strategies, substrates and catalysts

Preface SYNTHESIS OF NATURAL PRODUCTS CONTAINING MEDIUM-SIZE CARBOCYCLES BY RING-CLOSING ALKENE METATHESIS Introduction Formation of Five-Membered Carbocycles by RCM Formation of Six-Membered Carbocycles by RCM Formation of Seven-Membered Carbocycles by RCM Formation of Eight-Membered Carbocycles by RCM Formation of Nine-Membered Carbocycles by RCM Formation of 10-Membered Carbocycles by RCM Conclusion NATURAL PRODUCTS CONTAINING MEDIUM-SIZED NITROGEN HETEROCYCLES SYNTHESIZED BY RING-CLOSING ALKENE METATHESIS Introduction Five-Membered Nitrogen Heterocycles Six-Membered Nitrogen Heterocycles Seven-Membered Nitrogen Heterocycles Eight-Membered Nitrogen Heterocycles Conclusion SYNTHESIS OF NATURAL PRODUCTS CONTAINING MEDIUM-SIZE OXYGEN HETEROCYCLES BY RING-CLOSING ALKENE METATHESIS Introduction General RCM Approaches to Medium Rings Laurencin Eunicellins/Eleutherobin Helianane Octalactin A Microcarpalide and the Herbarums Marine Ladder Toxins Conclusion PHOSPHOROUS AND SULFUR HETEROCYCLES VIA RING-CLOSING METATHESIS: APPLICATION IN NATURAL PRODUCT SYNTHESIS Introduction Synthesis and Reactivity of Sulfones Derived from RCM Total Synthesis of the Originally Proposed Structure of (?)-Mycothiazole Synthesis and Reactivity of Phosphates from RCM Applications of Phosphate Tethers in the Synthesis of Dolabelide C Conclusion SYNTHESIS OF NATURAL PRODUCTS CONTAINING MACROCYCLES BY ALKENE RING-CLOSING METATHESIS Introduction Organization of the Chapter Macrocyclic Polyketides Terpenoids Macrocyclic Lipids Macrocyclic Glycolipids Conclusions and Outlook SYNTHESIS OF NATURAL PRODUCTS AND RELATED COMPOUNDS USING ENE-YNE METATHESIS Introduction Synthesis of Natural Products and Related Compounds Using Ene-Yne Metathesis Synthesis of Natural Products and Related Compounds Using Ene-Yne Cross-Metathesis (CM) Synthesis of Natural Products Using Skeletal Reorganization RING-CLOSING ALKYNE METATHESIS IN NATURAL PRODUCT SYNTHESIS Introduction Alkyne Metathesis Ring-Closing Alkyne Metathesis Applications of RCAM in Natural Product Synthesis Conclusions TEMPORARY SILICON-TETHERED RING-CLOSING METATHESIS REACTIONS IN NATURAL PRODUCT SYNTHESIS Introduction Temporary Silicon-Tethered Ring-Closing Metathesis Reactions Conclusions and Outlook METATHESIS INVOLVING A RELAY AND APPLICATIONS IN NATURAL PRODUCT SYNTHESIS Introduction Early Relay Metathesis Discoveries Examples of Relay Metathesis Directed at Targets Other tan Natural Products Examples of Relay Metathesis Motivated by Natural Product Synthesis Examples of Relay Metatheses Thwarted in Achieving the Desired Outcome Conclusion CROSS-METATHESIS IN NATURAL PRODUCT SYNTHESIS Introduction Functionalization of Olefins Appending a Side Chain Couplings Cascade Processes Involving CM Ene-Yne CM Alkyne CM Conclusion and Perspectives CASCADE METATHESIS IN NATURAL PRODUCT SYNTHESIS Introduction RCM-CM Sequences Ene-Yne-Ene RCM-RCM ROM-CM Sequences RCM-ROM Sequences - Ring-Rearrangement Metathesis (RRM) RCM-ROM Sequences Combined with Other Metathesis Reactions Conclusions and Outlook CATALYTIC ENANTIOSELECTIVE OLEFIN METATHESIS AND NATURAL PRODUCT SYNTHESIS Introduction Total Synthesis of Natural Products with Enantiomerically Pure Chiral Olefin Metathesis Catalysts Bearing a C2-Symmetric Diolate Ligand Enantioselective Synthesis of Quebrachamine through an Exceptionally Challenging RCM Reaction Synthesis of Baconipyrone C by Ru-Catalyzed Enantioselective ROCM Conclusions and Future Outlook METATHESIS REACTIONS IN SOLID-PHASE ORGANIC SYNTHESIS Introduction Metathesis-Based Cyclorelease Reaction Ring-Closing Metathesis (RCM) Intraresin Dimerization Restricting Peptide Conformation through Cyclization Cross-Metathesis on Solid Phase Ene-Yne Metathesis on Solid Phase Conclusion

Derivatives of 7-oxabicyclo[2.2.1]heptane in nature and as useful synthetic intermediates

Keywords: Diels-alder-reaction ; opening metathesis polymerization ; acid-catalyzed ; hydrolysis ; lithium aluminum-hydride ; soybean cyst nematode ; diastereoselective bis-hydroxylation ; thromboxane-a2 receptor ; antagonists ; enantioselective total synthesis ; wagner-meerwein ; rearrangements ; platelet-activating-factor Note: Univ Lausanne, Chim Sect, BCH, CH-1015 Lausanne, Switzerland. Ecole Super Phys & Chim Ind, Dept Chim Organ, F-75005 Paris 5, France. Univ Complutense Madrid, Fac Quim, Dept Quim Organ 1, E-28040 Madrid, Spain. Reference LGSA-ARTICLE-1999-014doi:10.1016/S0040-4020(99)00845-5 Record created on 2005-11-09, modified on 2017-05-12

FeCl3-Catalyzed Highly Diastereoselective Synthesis of Substituted Piperidines and Tetrahydropyrans

The eco-friendly and highly diastereoselective synthesis of substituted cis-2,6-piperidines and cis-2,6-tetrahydropyrans is described. The key step of this method is the iron-catalyzed thermodynamic equilibration of 2-alkenyl 6-substituted piperidines and 2-alkenyl 6-substituted tetrahydropyrans allowing the isolation of enriched mixtures of the most stable cis-isomers.

Olefin isomerization by a ruthenium carbenoid complex. Cleavage of allyl and homoallyl groups

Abstract Ruthenium–carbenoid catalysts such as Grubbs’ complex I mediate efficiently the isomerization of β,γ-unsaturated ethers and amines to the corresponding vinyl ethers and enamines. This reaction can be useful in the deprotection of allyl and homoallyl ethers as well as amines.

When cyclopropenes meet gold catalysts

Summary Cyclopropenes as substrates entered the field of gold catalysis in 2008 and have proven to be valuable partners in a variety of gold-catalyzed reactions. The different contributions in this growing research area are summarized in this review.

Regioselective ring opening of epoxides by nucleophiles mediated by lithium bistrifluoromethanesulfonimide

Abstract In the presence of LiNTf 2 , epoxides undergo ring opening with high regioselectivity and in good yield when they are treated with nucleophiles such as amines, hydrazines and thiophenol.

Synthesis of 3-Oxa- and 3-Azabicyclo[4.1.0]heptanes by Gold-Catalyzed Cycloisomerization of Cyclopropenes

Allyl 3,3-dimethylcyclopropenylcarbinyl ethers or sulfonamides undergo gold-catalyzed cycloisomerization leading to 5-isopropylidene-3-oxa- and 3-azabicyclo[4.1.0]heptanes in excellent yields and with high diastereoselectivities. These reactions constitute the first examples of intramolecular cyclopropanation of an alkene by a gold carbene generated by electrophilic ring opening of a cyclopropene in the presence of gold(I) chloride.

Ring Expansion – Formation of Optically Active 3‐Hydroxypiperidines from Pyrrolidinemethanol Derivatives

Treatment of pyrrolidinemethanol derivatives (–)-1, (–)-6, (–)-7, 8, (–)-9, (+)-10, (–)-11, and (–)-21 with trifluoroacetic anhydride and then with Et3N afforded, after hydrolysis of the trifluoroacetyl group with NaOH, the optically active 3-hydroxypiperidines (–)-14, (+)-15, (–)-16, 17, (+)-18, (–)-19, (–)-20, and (+)-22, respectively. The yields are good and the enantiomeric excess excellent (up to 95 %).

Intramolecular Cyclopropanation and C–H Insertion Reactions with Metal Carbenoids Generated from Cyclopropenes

Activation of unsaturated carbon-carbon bonds by means of transition metal catalysts is an exceptionally active research field in organic synthesis. In this context, due to their high ring strain, cyclopropenes constitute an interesting class of substrates that displays a versatile reactivity in the presence of transition metal catalysts. Metal complexes of vinyl carbenes are involved as key intermediates in a wide variety of transition metal-catalyzed ring-opening reactions of cyclopropenes. Most of the reported transformations rely on intermolecular or intramolecular addition of nucleophiles to these latter reactive species. This Account focuses specifically on the reactivity of carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation and C-H insertion reactions, which are arguably two of the most representative transformations of metal complexes of carbenes. Compared with the more conventional α-diazo carbonyl compounds, the use of cyclopropenes as precursors of metal carbenoids in intramolecular cyclopropanation or C-H insertion reactions has been largely underexploited. One of the challenges is to devise appropriately substituted and readily available cyclopropenes that would not only undergo regioselective ring-opening under mild conditions but also trigger the subsequent desired transformations with a high level of chemoselectivity and stereoselectivity. These goals were met by considering several substrates derived from the readily available 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective gold(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as a route to diversely substituted heterocycles and carbocycles possessing a bicyclo[4.1.0]heptane framework. The use of rhodium(II) catalysts enabled us to widen the scope of this transformation for the synthesis of medium-sized heterocyclic scaffolds incorporating an eight-membered ring. The reactivity of rhodium(II) carbenoids generated from 3,3-dimethylcyclopropenylcarbinols was also investigated in intramolecular C(sp(3))-H insertions. Despite their low electrophilic character, these purely donor rhodium(II) carbenoids underwent remarkably efficient diastereoselective 1,5- or 1,6-C-H insertions allowing access to a wide variety of substituted cyclopentanols, cyclohexanols, bicycloalkanols, and tetrahydropyrans with high level of diastereoselectivity and with complete tolerance of a free hydroxyl group. The products arising from the gold(I)- or rhodium(II)-catalyzed ring-opening/intramolecular cyclopropanation or C-H insertion of 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines always incorporate an isopropylidene moiety, which can potentially undergo subsequent oxidative cleavage into a carbonyl group without epimerization. By virtue of this operation, the 3,3-dimethylcyclopropenyl group formally behaves as a valuable surrogate for an α-diazoketone, with obvious advantages considering the ease of access to the corresponding substrates and that no hazardous reagents are involved in their preparation. These studies have set a useful basis for the development of other reaction pathways involving metal carbenoids generated from these readily available families of substituted cyclopropenes, including the investigation of the yet underexploited synthetic potential of purely donor rhodium(II) carbenoids.

Synthesis of oxygenated heterocycles from cyclic allylsiloxanes using ring-closing olefin metathesis

Abstract Cyclic allylsiloxanes were prepared from allyldimethylsilyl ethers of various alkenols by using a catalytic ring-closing metathesis (RCM) reaction. The transformation of these cyclic allylsiloxanes into stereoselectively substituted tetrahydrofurans and tetrahydropyrans was achieved by using a silyl modified Sakurai reaction.