Carbonyl-Olefin Metathesis

Abstract

This Review describes the development of strategies for carbonyl-olefin metathesis reactions relying on stepwise, stoichiometric, or catalytic approaches. A comprehensive overview of currently available methods is provided starting with Paternò-Büchi cycloadditions between carbonyls and alkenes, followed by fragmentation of the resulting oxetanes, metal alkylidene-mediated strategies, [3 + 2]-cycloaddition approaches with strained hydrazines as organocatalysts, Lewis acid-mediated and Lewis acid-catalyzed strategies relying on the formation of intermediate oxetanes, and protocols based on initial carbon-carbon bond formation between carbonyls and alkenes and subsequent Grob-fragmentations. The Review concludes with an overview of applications of these currently available methods for carbonyl-olefin metathesis in complex molecule synthesis. Over the past eight years, the field of carbonyl-olefin metathesis has grown significantly and expanded from stoichiometric reaction protocols to efficient catalytic strategies for ring-closing, ring-opening, and cross carbonyl-olefin metathesis. The aim of this Review is to capture the status quo of the field and is expected to contribute to further advancements in carbonyl-olefin metathesis in the coming years.

Figure 1.

Olefin-Olefin Metathesis (A) versus Carbonyl-Olefin Metathesis (B).

Figure 2.

Overview of Currently Available Strategies for Carbonyl-Olefin Metathesis.

Figure 3.

Classes of Olefin-Olefin Metathesis and Carbonyl-Olefin Metathesis Reactions Developed.

Scheme 1.

Paternò-Büchi Reaction

Scheme 2.

Photo-Induced Oxetane Formation of Norbornene and Benzophenone by Scharf and Korte

Scheme 3.

Structural Elucidation of Oxetanes via Acid-Mediated Fragmentations by Kohler and Richtmeyer

Scheme 4.

Rh(I)-Catalyzed Rearrangements of Vinyl Oxetanes by Grigg

Scheme 5.

Photolysis-Pyrolysis Sequence for Carbonyl–Olefin Metathesis by Jones

Scheme 6.

Formation of Long-Chain Enals via Carbonyl-Olefin Metathesis by Jones

Scheme 7.

Lewis Acid Fragmentation of Oxetanes by Carless

Scheme 8.

Flow Pyrolysis of Fluorinated Oxetanes by Barlow, Coles, and Haszeldine

Scheme 9.

Thermal Fragmentation 2-Aryl Substituted Oxetanes by Nishida

Scheme 10.

Pyrolysis of Keto Oxetanes by Maruyama

Scheme 11.

Photosensitized Ring-Cleavage in the Presence of Electron Acceptors by Shima

Scheme 12.

Photosensitized Ring-Cleavage in the Presence of an Electron Donor by Shima

Scheme 13.

Photochemical Cycloreversion of Methoxynaphthalene-Oxetane Dyads by Miranda

Scheme 14.

Carbonyl-Olefin Metathesis of Bicyclic Oxetanes by Miranda and Griesbeck

Scheme 15.

Photoprotolytic Oxametathesis in Polycyclic Systems by Kutateladze

Scheme 16.

Oxetane Formation vs. Metathesis by D'Auria

Scheme 17.

Photoprotolytic Oxametathesis Leading to Molecular Complexity by Kutateladze

Scheme 18.

High-Yielding Photoprotolytic Oxametathesis in Polycyclic Systems by Kutateladze

Scheme 19.

Strategies for Metathesis with Metal Alkylidenes

Scheme 20.

Application of Strategy I by Grubbs

Scheme 21.

Fischer and Schrock Metal-Carbenes

Scheme 22.

Carbonyl-Olefin Metathesis Used for Endcapping Reactions of Polymers by Grubbs

Scheme 23.

Olefin Metathesis and Carbonyl Olefination by Grubbs

Scheme 24.

Application of Strategy II for the Conversion of Olefinic Esters to Cyclic Enol Ethers by Nicolaou

Scheme 25.

Iterative Pathway Towards Fused Ether Ring Systems by Allwein and Rainier

Scheme 26.

Mechanism of the Takai-Utimoto Conditions

Scheme 27.

Synthetic Route to Benzo-Fused N-heterocycles by Bennasar

Scheme 28.

Modified Takai-Utimoto Reduced Titanium Reagent for the Olefinic Ester Cyclization by Rainier

Scheme 29.

Reactivity of Reduced Titanium Alkylidenes for Cyclic Enol Ether Formation by Rainier and Iyer

Scheme 30.

Polycyclic Ether Skeletons Synthesis by Rainier

Scheme 31.

Olefinic Lactone Cyclization by Rainier

Scheme 32.

Synthesis of Cyclic Enamides by Rainier

Scheme 33.

Ruthenium Alkylidene-Mediated Carbonyl-Olefin Metathesis as Reported by Chakraborty and Roy

Scheme 34.

Carbonyl-Olefin Exchange Reactions Enabling Polymerizations

Scheme 35.

Carbonyl-Olefin Exchange Reaction as Synthetic Route to Polyconjugated Polymers by Schopov

Scheme 36.

General Formulas and Examples of Conjugated Polymers Obtained with Carbonyl-Olefin Exchange Reaction

Scheme 37.

Types of Propagation Steps Proposed by Jossifov

Scheme 38.

Possible Mechanism for the Synthesis of Polyconjugated Polymers by Schopov and Jossifov

Scheme 39.

Synthesis of Tungsten Metallaoxirane and Tungsten Oxo-Alkylidene Complexes by Mayer

Scheme 40.

Synthesis of polyphenylacetylene by iron(III) chloride by Dimova

Scheme 41.

Reaction Design Principle for the First Catalytic Carbonyl-Olefin Metathesis Reaction.

Scheme 42.

Catalytic Ring-Opening Carbonyl-Olefin Metathesis via 1,3-Dipolar Cycloadditions.

Scheme 43.

Hydrazine-Catalyzed Ring-Opening Carbonyl–Olefin Metathesis by Lambert.

Scheme 44.

Distortion-Accelerated and Strain-Release-Promoted [3+2] and retro-[3+2] in Organocatalytic Carbonyl-Olefin Metathesis by Lambert and Houk.

Scheme 45.

Hydrazine-Catalyzed Ring-Opening Carbonyl-Olefin Metathesis of Norbornenes by Lambert.

Scheme 46.

Catalytic Ring-Closing Carbonyl-Olefin Metathesis via 1,3-Dipolar Cycloadditions.

Scheme 47.

Synthesis of 2H-Chromenes via Hydrazine-Catalyzed Carbonyl–Olefin Metathesis by Lambert

Scheme 48.

Synthesis of 1,2-Dihydroquinolines via Hydrazine-Catalyzed Carbonyl–Olefin Metathesis by Lambert

Scheme 49.

Lewis Acid-Catalyzed Carbonyl-Olefin Metathesis

Scheme 50.

Lewis acid-mediated metathesis reactions by Demole and Snider.

Scheme 51.

Solid Promoted Lewis Acid-Promoted Carbonyl-Olefin Metathesis by Bickelhaupt and Coworkers

Scheme 52.

Lewis Acid-Promoted Transannular Carbonyl-Olefin Metathesis by Khripach and Coworkers

Scheme 53.

BF₃·OEt₂ Induced Metathesis Cyclization of Pestalone Derivatives by Schmalz and Coworkers

Scheme 54.

Initial Studies of Carbonyl-Olefin Ring-Closing Metathesis by Schindler and Coworkers Show Several Lewis Acids Capable of Promoting the Desired Transformation

Scheme 55.

Scope of the FeCl₃-Catalyzed Carbonyl-Olefin Ring-Closing Metathesis Reaction

Scheme 56.

Two Mechanistic Alternatives for FeCl₃-Catalyzed Carbonyl-Olefin Ring-Closing Metathesis

Scheme 57.

Organic Synthesis Procedure Developed for FeCl₃-Catalyzed Carbonyl-Olefin Ring-Closing Metathesis

Scheme 58.

FeCl₃-Catalyzed Carbonyl-Olefin Ring-Closing Metathesis by Li and Coworkers

Scheme 59.

Mechanistic Investigations of Prenylated β-Ketoesters in Fecl₃-Catalyzed Carbonyl-Olefin Metathesis by Schindler, Devery, Zimmerman, and Coworkers

Scheme 60.

Mechanistic Investigations of Styrenyl-derived β-Ketoesters in FeCl₃-Catalyzed Carbonyl-Olefin Metathesis by Schindler, Devery, Zimmerman, and Coworkers

Scheme 61.

Carbonyl-Olefin Metathesis (359) versus Interrupted Carbonyl-Olefin Metathesis Reactions (361).

Scheme 62.

Fecl₃ Catalyst Behavior and Solution Structure Investigated by Devery and Coworkers

Scheme 63.

Formation of 2,5-Dihydropyrroles in Fecl₃-Catalyzed Carbonyl-Olefin Metathesis by Li and Coworkers

Scheme 64.

N-Containing Substrates for Carbonyl-Olefin Metathesis by Schindler and Coworkers

Scheme 65.

Carbocation-Catalyzed Carbonyl-Olefin Ring-Closing Metathesis by Franzén and Coworkers

Scheme 66.

Approaches to Carbonyl-Olefin Ring-Closing Metathesis Relying on Tropylium Cations, Iodine, and AuCl₃ as Lewis Acid Catalysts by Nguyen and Lin

Scheme 67.

Carbonyl-Olefin Ring-Closing Metathesis and Transfer Hydrogenation by Gandon and Bour

Scheme 68.

Duñach Observes the Formation of Carbonyl-Olefin Ring-Closing Metathesis Product 395 in Studies of Intramolecular Carbonyl-Ene Reactions

Scheme 69.

Limited Examples for Cyclohexene Products Formed in Catalytic Carbonyl-Olefin Ring-Closing Metathesis by Schindler and Coworkers

Scheme 70.

Carbonyl-Olefin Metathesis Towards Polycyclic Aromatic Hydrocarbons by Schindler and Coworkers

Scheme 71.

Investigation of the Carbonyl Scope in Catalytic Carbonyl-Olefin Metathesis Reactions by Schindler and Coworkers

Scheme 72.

Approaches to Carbonyl-Olefin Ring-Closing Metathesis Relying on Tropylium Cations, Iodine, and AuCl₃ as Lewis Acid Catalysts for the Formation of Polyaromatic Hydrocarbons by Nguyen and Lin

Scheme 73.

Divergent Reactivity Observed in Carbonyl-Olefin Metathesis and Carbonyl-Ene Reactions is not Exclusively Explained by Lewis Acidity as Reported by Schindler and Reid

Scheme 74.

Mechanistic Hypothesis for Competing Carbonyl-Olefin Metathesis and Carbonyl-Ene Reactions of Biaryl Aldehydes by Schindler and Reid

Scheme 75.

Tetrahydropyridines via FeCl₃-Catalyzed Carbonyl-Olefin Metathesis by Schindler and Coworkers

Scheme 76.

Lewis Acidic “Superelectrophiles” as Stronger Catalysts for Carbonyl-Olefin Metathesis as Suggested by Schindler and Coworkers

Scheme 77.

Formation of 6-Membered Rings from Acyclic Arylketones developed by Schindler and coworkers

Scheme 78.

Al(III)-Ion Pairs Promote Carbonyl-Olefin Metathesis via a Distinct Reaction Path by Schindler and Coworkers

Scheme 79.

Au(III)-Catalyzed Carbonyl-Olefin Ring-Closing Metathesis for the Formation of 6- and 7-Membered Rings by Lin and Coworkers

Scheme 80.

Challenges in Lewis Acid-Catalyzed Carbonyl-Olefin Metathesis Reactions of Aliphatic Ketones

Scheme 81.

Carbonyl-Olefin Metathesis of Aliphatic Ketones by Schindler and Coworkers

Scheme 82.

FeCl₃-Homodimers as Active Catalytic Species in the Carbonyl-Olefin Metathesis of Aliphatic Ketones as Proposed by Schindler and Coworkers

Scheme 83.

Lewis Acid-Catalyzed Intramolecular Carbonyl-Ene Reactions Reported by Duñach and Coworkers

Scheme 84.

E-Selective Cross-Metathesis by Franzén and Coworkers

Scheme 85.

Mechanistic Hypothesis for Catalytic Cross Carbonyl-Olefin Metathesis

Scheme 86.

Tropylium-Ions and Iodine as Lewis Acid Catalysts in Intermolecular Carbonyl-Olefin Cross Metathesis Reactions by Nguyen and Coworkers

Scheme 87.

E-Selective Intermolecular Carbonyl-Olefin Metathesis by Schindler and Coworkers

Scheme 88.

E-Selectivity due to Regioselective Oxetane Formation

Scheme 89.

Ring-Opening Carbonyl-Olefin Metathesis by Schindler and Coworkers

Scheme 90.

Carbonyl-Olefin Metathesis and Carbonyl-Ene Reaction Paths Compete in Catalytic Ring-Opening Reactions as Proposed by Schindler and Coworkers

Scheme 91.

Tropylium-Ions and Iodine as Lewis Acid Catalysts in Intermolecular Carbonyl-Olefin Ring-Opening Metathesis Reactions by Nguyen and Coworkers

Scheme 92.

Catalytic, Transannular Carbonyl-Olefin Metathesis by Schindler and Coworkers

Scheme 93.

Divergent Reactivity in Transannular Reactions of Unsaturated, Cyclic Ketones 524 with Me₂AlC, FeCl₃, or TiCl₄ as Lewis Acid

Scheme 94.

Mechanistic Hypothesis for Catalytic, Transannular Carbonyl-Olefin Metathesis by Schindler and Coworkers

Scheme 95.

Brønsted Acid-Catalyzed Metathesis in a Self-Assembled Supramolecular Host by Tiefenbacher

Scheme 96.

Cross Carbonyl-Olefin Metathesis Relying on Grob Fragmentations

Scheme 97.

Carbonyl–Olefin Cross-Metathesis via Visible-Light-Induced 1,3-Diol Formation and Fragmentation Sequence by Glorius

Scheme 98.

Intermolecular Carbonyl-Olefin Metathesis of Vinyl Ethers Catalyzed by Solid Acids in Flow by Leyva-Pérez

Scheme 99.

Synthesis of the Mediterranean Fruit Fly Pheromone trans-Non-6-en-1-ol by Jones

Scheme 100.

Synthesis of (±)-Capnellene by Grubbs and Stille

Scheme 101.

Structure of Maitotoxin, a Natural Toxin Produced by Gambierdiscus toxicus

Scheme 102.

Synthesis of Maitotoxin Subunits Relying on Carbonyl-Olefin Metathesis by Nicolaou and Coworkers

Scheme 103.

Strategy Towards Hemibrevetoxin B by Rainier and Coworkers

Scheme 104.

Strategy Towards Gambieric acids by Rainier and Coworkers

Scheme 105.

Strategy Towards Brevenal by Rainier and Coworkers

Scheme 106.

Strategy Towards Bryostatin 1 by Keck and Coworkers

Scheme 107.

Synthesis of (±)-Cocculidine by Sarpong and Coworkers

Scheme 108.

Synthesis of Huperzine Q, Lycoplanadine B and C by Lei and Coworkers