Michael reaction mechanism what anions are favorable michael donors. Synthetic planning directed to conjugated octalones, of the type 1, traditionally tends to center around enolate and enol based progressions inherent in the expression robinson annulation ra, see eq. Robinson annulation and its concept were confined to the synthesis of sixmembered carbocycles till 1958, when mccoy reported an application of the concept in the synthesis of cyclopropane dicarboxylates. Draw a stepwise mechanism for the following robinson annulat. Lab 1 asymmetric synthesis of the wielandmiescher ketone chem 30cl student handout 1. A onepot, asymmetric robinson annulation in the organic chemistry majors laboratory. The experiment is further used to strength the students background in the chemoselective reactivity of enones direct vs conjugate additions, and the usefulness of the robinson annulation for ring synthesis. It is then this enolate that attacks the other carbonyl group to form a sixmembered ring one that does not have baeyer strain and is generally the most. Z energies, and pcm solvation corrections were used to characterize all intermediates. The robinson annulation is an organic reaction used to convert a ketone and an. The robinson annulation is a useful reaction for the formation of sixmembered rings in polycyclic compounds, such as steroids.
A common synthetic annulation reaction is the robinson annulation. H3c o the next mechanisms was the aldol condensation which is involving. You may do so in any reasonable manner, but not in. By pure chance, the two great men met early in a monday morning on an oxford train station platform in 1951. Permuting dielsalder and robinson annulation stereopatterns. Show product including stereochemistry, if appropriate. Mechanism and origin of stereoselectivity in robinson. These are the sources and citations used to research robinson annulation lab report. The robinson annulation or robinson annelation is a chemical reaction used in organic chemistry for ring formation. The reaction is named after its inventor sir robert robinson 1947 nobel laureate. The mechanism begins with deprotonation with the base of the. A complex sequence that can be used to form bicyclic systems containing a substituted cyclohexenone system. The first step in the process is the michael addition to an. Ethoxide ion is used as the base in the condensation above to avoid some unwanted reactions.
The method uses a ketone and a methyl vinyl ketone to form an. In a regular robinson annulation, as ron described, the michael acceptor system can be enolised on the far side of the ketone the one where your molecule has a phenyl group. With ordinary carbonyl substances the robinson annulation is poor mainly because of polymerization of the vinyl ketone, initiated by strongly basic enolates, and also because of the inability of controlling the site of anion formation. The process is called the robinson annulation annulation ring formation. Robinson annulation or robinson annelation is a synthetic protocol used to construct cyclohexane rings. The robinson annulation reaction university of calgary. The year 1958 was the year for cyclopropane synthesis.
Ruben martinez ring construction via annulation baran group meeting 011616 robinson annulation some important masked michael acceptors initial report general note o et2n o n et et me i functionalized products ome o o o o 1 nanh2 o 2ph 3 acidic workup o ph robinson, j. Robert robinson used the robinson annulaton in his total synthesis of cholesterol. These studies yielded a singlestep annulation that provided 5 in 49% yield and 76% ee in 89 h. Preparation of chalcone and its further robinson annulation. In a second step the methyl group adjacent to the carbonyl is deprotonated and undergoes an. Lab 1 asymmetric synthesis of the wielandmiescher ketone. This reaction was a key step in a synthesis of the steroid cortisone by r. As illustrated in the following figure, the robinson annulation reaction involves two steps. Provide a mechanism for the following claisen condensation. An annulation is defined as a transformation of one or more acyclic precursors resulting in the fusion of a new ring via two newly generated bonds. Mechanistically, robinson annulation is michael addition followed by intramolecular aldol condensation. The stepbystep robinson annulation of chalcone and ethyl acetoacetate is presented as an example of a fundamental organic reaction that can be investigated at several different levels. A robinson annulation reaction took place between transchalcone and ethyl acetoacetate in a basic solution of absolute ethanol, water, and sodium hydroxide.
Conjugate addition, then intramolecular aldol and finally an elimination. Organic chemistry chemistry 251 exam 2 100 points this is the second of four midterm exams and covers the chapters on enolates and synthesis. It provides plenty of synthesis examples and practice problems. These strategies can be used to create aromatic systems from acyclic precursors in a single step, with many substituents already in place. Robinson annulation an overview sciencedirect topics. This procedure is one of the key methods to form fused ring systems. Pdf the robinson annulation reaction idayu razali academia.
The robinson annulation reaction university of calgary in. Swirl the flask until the solid dissolves and place a boiling stone in the flask. The robinson annulation can also proceed under acidic catalysis, with the entire process occurring in one pot, as shown below. Computational studies on the mechanism and diastereoselectivity of base catalyzed synthesis of bicyclo3. Ring construction via annulation baran group meeting. On the structures provided below, show electron flow with arrows in this interesting reaction.
Provided the success of antibody catalysis of both steps of the annulation reaction and the reported utility of rubidium salts of lproline in asymmetric michael addition reactions,3 we examined the potential of lproline to catalyze the entire annulation reaction. Robinson annulation lab report chemistry bibliographies. The stepbystep robinson annulation of chalcone and ethyl. Show what side reactions would occur if the following bases were used. Robinson annulation retrosynthesis reaction mechanism.
Under appropriate experimental conditions, it is possible to stop the reaction after every step and to isolate the three products separately. Its a michael addition followed by an intramolecular aldol condensation, and it makes a ring. Robinson annulation is one notable example of a wider class of chemical transformations termed tandem michaelaldol reactions, that sequentially combine michael addition and aldol reaction into a single reaction. This annulation provides an efficient route to form an aromatic ring in one step. Jan 04, 2015 the robinson annulation is really neat, you guys. This file is licensed under the creative commons attributionshare alike 3. It is a thermal combination of a substituted cyclobutenones with heterosubstituted acetylenes to produce highly substituted aromatic compounds, specifically phenols or resorcinols scheme 1.
Computational study of the mechanisms and stereoselectivities of a dual aminocatalyzed synthesis of cyclohexenones containing allcarbon. As is the case with robinson annulation, michael addition usually happens first to tether the two reactants together, then aldol. Experiments on the synthesis of substances related to the sterols. The danheiser benzannulation is a regiocontrolled phenol annulation. How would you prepare these compounds using either an acetoacetic ester synthesis or a malonic ester synthesis. Draw a stepwise mechanism for the following robinson. The robinson annulation combines a michael reaction with an intramolecular aldol. This video discusses the mechanism of the robinson annulation which involves the reaction of cyclohexanone with a michael acceptor such as.
Introduction the robinson annulation is the michael addition followed by a simple. A prolinecatalyzed asymmetric robinson annulation reaction. The last step, after the aldol condensation, is an e1cb elimination and the mechanism for this reaction is covered in the aldol condensation post. The robinson annulation reaction combines a ketone with an alpha beta unsaturated ketone to produce a 1,5 dicarbonyl compound which. Chemistry 106 laboratory robinson annulation equation. It was discovered by robert robinson in 1935 as a method to create a six membered ring by forming three new carboncarbon bonds. Robinson annulation is the addition of methyl vinyl ketone to a cyclohexanone to form an.
Extensive conformational search with density functional theory optimizations, the highaccuracy scsmp2ccpv. Jan 01, 2012 synthetic planning directed to conjugated octalones, of the type 1, traditionally tends to center around enolate and enol based progressions inherent in the expression robinson annulation ra, see eq. Ethoxide ion is used as the base in the condensation above to avoid some unwanted. The aldol condensation is the second step of the robinson annulation. Woodward and coworkers at harvard university in 1951. A prolinecatalyzed asymmetric robinson annulation reaction tommy bui, carlos f. Lets put together a complete mechanism for the robinson annulation. The first step in the robinson annulation is a michael reaction to form a 1,5dicarbonyl compound. Objectives in this laboratory, we will perform an asymmetric robinson annulation using proline, an organocatalyst. Mechanism and stereoselectivity of a dual aminocatalyzed. Here is a story told by derek barton about robinson and woodward.
Three possible mechanisms were considered, and only the methanol assisted h. Request pdf robinson annulation michael addition of cyclohexanones to methyl vinyl ketone followed by intramolecular aldol condensation to afford. Over the course of three lab periods, you will synthesize and purify wielandmiescher ketone, a versatile building block for the syntheses of many natural products. Annulation types and varieties spiroannulationbenzannulation two carbon annulation three carbon annulation four carbon annulation robinson type four carbon annulation nonrobinson type five carbon annulation the focus of this seminar will be methods for ring construction that can be used as a. An efficient method for the selective iodination of. Organic chemistry chemistry 251 university of puget sound. This reaction proceeds by a reverse claisen condensation mechanism followed by a recyclization. Robert robinson won the nobel prize for chemistry in 1947 for his contribution to the study of alkaloids.
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