Robinson annulation retrosynthesis reaction mechanism. Robinson annulation reaction of transchalcone with ethyl acetoacetate. Preparation of chalcone and its further robinson annulation. I think many people have not been connecting the mechanisms with the overall reactions we have been discussing. As a group, work out the detailed mechanism for the robinson annulation reaction between.
Predict the product in the following michael reaction. Predict the product of the following stork enamine reaction. Chemistry 106 laboratory robinson annulation equation. 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. In this present work, a general approach to the mild synthesis of substituted cyclohex2enones derivatives starting fro m simple aldehydes and acetone have been achieved via daminoacylaseinitiated aldol condensationrobinson annulation cascade reaction using. You may do so in any reasonable manner, but not in. Why does no robinson annulation occur after the michael addition. Ring construction via annulation baran group meeting. A prolinecatalyzed asymmetric robinson annulation reaction. The formation of the conjugated system is the driving force for this spontaneous dehydration. 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.
Media in category robinson annulation the following 26 files are in this category, out of 26 total. The year 1958 was the year for cyclopropane synthesis. The robinson annulation represents a tandem process including the michael addition and intramolecular aldol condensation, affording biscyclo4. When the product of a michael reaction is treated with naoh, h 2 o, and heat, a robinson annulation. Pdf the robinson annulation reaction idayu razali academia. Files are available under licenses specified on their description page. Michael reaction mechanism what anions are favorable michael donors. Mechanisms mechanisms for michael addition reaction which is involving the trans. As an important building block, developing efficient and green synthesis strategy of cyclohex2enones is of great importance. 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. Mechanism and stereoselectivity of a dual aminocatalyzed.
Annulation is a term that describes the formation of a ring. It is a thermal combination of a substituted cyclobutenones with heterosubstituted acetylenes to produce highly substituted aromatic compounds, specifically phenols or resorcinols scheme 1. The robinson annulation reaction combines a ketone with an alpha beta unsaturated ketone to produce a 1,5 dicarbonyl compound which. The reaction begins with a michael reaction, followed by an intramolecular aldol condensation to give a new sixmembered ring containing an alpha, beta unsaturated ketone. The danheiser benzannulation is a regiocontrolled phenol annulation. The original procedure of the robinson annulation begins with the nucleophilic attack of a ketone in a michael reaction on a vinyl ketone to produce the intermediate michael adduct. As illustrated in the following figure, the robinson annulation reaction involves two steps. This feature is particularly attractive in the frame of an organic chemistry course. Robert robinson won the nobel prize for chemistry in 1947 for his contribution to the study of alkaloids. Conjugate addition, then intramolecular aldol and finally an elimination. It is a classic example of a tandem or cascade reaction, where an initial reaction provides the starting material for a successive reaction. Robinson annulation is also used for synthesizing spirocyclic compounds. This file is licensed under the creative commons attributionshare alike 3.
Introduction the robinson annulation is an organic reaction used to convert a ketone and an. Swirl the flask until the solid dissolves and place a boiling stone in the flask. 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. The robinson annulation reaction university of calgary. A common synthetic annulation reaction is the robinson annulation.
Mechanistically, robinson annulation is michael addition followed by intramolecular aldol condensation. The robinson annulation is a useful reaction for the formation of sixmembered rings in polycyclic compounds, such as steroids. When you look at a mechanism, make sure you can explain exactly what every component of the reaction is doing. In some cases, the adducts obtained from the aldol addition can easily be converted in situ to. The robinson annulation is a combination of two ca. Under appropriate experimental conditions, it is possible to stop the reaction after every step and to isolate the three products separately. The process begins with a michael reaction and ends with an intramolecular aldol condensation to give the new ring. General features both acid and basecatalyzed, but predominantly. These studies yielded a singlestep annulation that provided 5 in 49% yield and 76% ee in 89 h.
The activated methylene is essentially a methylene bonded to electron withdrawing groups that would stabilize the negative change that forms after deprotonation by the base. The robinson annulation is the name for a process that combines two key reactions youve learned previously into one longer sequence. 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. It has come to my attention that some of you are not familiar with a robinson annulation reaction, so we are going to do a 2. This annulation provides an efficient route to form an aromatic ring in one step. This video discusses the mechanism of the robinson annulation which involves the reaction of cyclohexanone with a michael acceptor such as.
Request pdf a prolinecatalyzed asymmetric robinson annulation reaction a singlestep enantioselective synthesis of the wielandmiescher ketone 5 is presented. 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. These strategies can be used to create aromatic systems from acyclic precursors in a single step, with many substituents already in place. Methyl vinyl ketone or variants thereof are essential for the annulation as they are simultaneously a michael acceptor and able to take part in an aldol condensation. The first step in the robinson annulation also spelt annelation is a michael addition followed by an aldol reaction as the annulation step in. Subsequent aldol type ring closure leads to the keto alcohol, which is then followed by dehydration to produce the annulation product. The stepbystep robinson annulation of chalcone and ethyl. Request pdf robinson annulation michael addition of cyclohexanones to methyl vinyl. Many asymmetric variants exist in this scheme the r and r substituents on the nucleophile a michael donor are. The most common partners in the reaction are a nucleophilic donor such as a cyclic ketone, a bketo ester, an enamine, or a. Here is a story told by derek barton about robinson and woodward. By pure chance, the two great men met early in a monday morning on an oxford train station platform in 1951. The first step in the process is the michael addition to an. The robinson annulation reaction chemistry libretexts.
The robinson annulation is a useful reaction for the formation of sixmembered rings in polycyclic compounds, such as. This deprotonation results in an enolate which in turn does a 1,4 addition to the conjugated olefin. Organic chemistry chemistry 251 exam 2 100 points this is the second of four midterm exams and covers the chapters on enolates and synthesis. The robinson annulation is a combination of two carbonyl coupling reactions, the michael reaction and the intramolecular aldol condensation. For those needing a refresher on the mechanism, click here to see a popup image.
The robinson annulation or robinson annelation is a chemical reaction used in organic chemistry for ring formation. This is one of the most useful methods for the mild formation of cc bonds. The method uses a ketone and a methyl vinyl ketone to form an. Others, however, insist that such a usage is an abuse of terminology, and limit the michael addition to the formation of carboncarbon bonds through the addition of carbon nucleophiles. The michael addition is an organic reaction used to convert an activated methylene and a conjugated olefin to the corresponding addition product using a base catalyst followed by an acid workup. Explain why the michael reaction of 2phenylcyclohexanone with 2propenenitrile gives the product shown in the equation on page 894 rather than this product. A singlestep enantioselective synthesis of the wielandmiescher ketone 5 is presented. The robinson annulation is a chemical reaction used in organic chemistry for ring formation. The terms oxamichael reaction and azamichael reaction have been used to refer to the 1,4addition of oxygen and nitrogen nucleophiles, respectively. The robinson annulation reaction department of chemistry. Z energies, and pcm solvation corrections were used to characterize all intermediates. A complex sequence that can be used to form bicyclic systems containing a substituted cyclohexenone system. The robinson annulation can also proceed under acidic catalysis, with the entire process occurring in one pot, as shown below.
The merits of the robinson annulation lie in its applicability in the total synthesis of. For some arrows, more than one step may be necessary. One of the many applications of robinson annulation is in the synthesis of estrone, a steroid hormone. It belongs to the larger class of conjugate additions. Robinson annulation an overview sciencedirect topics. The robinson annulation is an organic reaction used to convert a ketone and an. The mechanism begins with deprotonation with the base of the. The enolate then does a 1,4 addition to the conjugated olefin. The michael reaction or michael addition is the nucleophilic addition of a carbanion or another nucleophile to an. Show product including stereochemistry, if appropriate. All structured data from the file and property namespaces is available under the creative commons cc0 license. The activated methylene is essentially a methylene bonded to electron withdrawing groups that would stabilize the negative change that forms after. The michael reaction in combination with an aldol condensation provides a useful method for the construction of sixmembered rings in a process termed the robinson annulation.
This organic chemistry video tutorial provides a basic introduction into the robinson annulation mechanism which is a combination of a michael addition reaction and an intramolecular aldol reaction. Diels alder class 3, 2011 uri department of chemistry. Robert robinson used the robinson annulaton in his total synthesis of cholesterol. Sibi lecture 34 during the second world war, synthesis of steroids became very important. This page was last edited on 28 november 2016, at 05. It was discovered by robert robinson in 1935 as a method to create a six membered ring by forming three new carboncarbon bonds. We show that lproline as well as a number of other chiral amines can act as catalysts of both steps of the robinson annulation reaction. Its a michael addition followed by an intramolecular aldol condensation, and it makes a ring. Robinson annulation or robinson annelation is a synthetic protocol used to construct cyclohexane rings. The robinson annulation combines a michael reaction with an intramolecular aldol.
It provides plenty of synthesis examples and practice problems. Introduction the robinson annulation is the michael addition followed by a. An acid workup then provides the final michael addition product. Robinson reaction is a michael reaction followed by an aldol condensation. The most common partners in the reaction are a nucleophilic donor such as a cyclic ketone, a. Computational study of the mechanisms and stereoselectivities of a dual aminocatalyzed synthesis of cyclohexenones containing allcarbon. Extensive conformational search with density functional theory optimizations, the highaccuracy scsmp2ccpv. The robinson annulation is a threestep process involving a michael addition followed by an internal aldol condensation and a dehydration. Jan 04, 2015 the robinson annulation is really neat, you guys. In a second step the methyl group adjacent to the carbonyl is deprotonated and undergoes an. Mechanism, references and reaction samples of the stobbe condensation. Mechanism, key deprotonation step mixed claisen dieckmann cyclization favorable ring sizes, etc.