Enantioselective solvent free robinson annulation reactions 201 our attempts to cyclize the trione 27 using proline were unsuccessful. Request pdf robinson annulation michael addition of cyclohexanones to methyl vinyl. A prolinecatalyzed asymmetric robinson annulation reaction. It combines two reactions the michael addition and the aldol condensation. The robinson annulation involves two sequential reactions, a michael addition and an aldol condensation, resulting in the formation of a cyclohexenone derivative. The robinson annulation reaction department of chemistry. The cyclizations were carried out under n itrogen atmosphere in the neat 2.
It was discovered by robert robinson in 1935 as a method to create a six membered ring by forming three new carboncarbon bonds. As illustrated in the following figure, the robinson annulation reaction involves two steps. The robinson annulation is a combination of two ca. The robinson annulation is a chemical reaction used in organic chemistry for ring formation. View notes robinson annulation from chem 204 at montgomery college. 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. The link will proceed how you will get the organic chemistry smith 3rd edition solutions manual free. 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. Its a michael addition followed by an intramolecular aldol condensation, and it makes a ring.
Robinson annulationdirected synthesis of jetfuelranged. There are three types of crossed aldol condensations that give only one major product. The robinson annulation forms a sixmembered ring and three new carboncarbon bondstwo. 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 was found that the reaction with 20 mol% of cat1 gave the desired product 3a in 79% yield with 5. 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. Assembly of the contiguous trisubstituted olefin component. Antibodycatalyzed enantioselective robinson annulation. The optically active enediones obtained in the above cyclizations could also be obtained directly from 1,3diones or 2hydroxymethylene cycloalkanones in a onepot reaction with methyl vinyl ketone mvk and sproline in the absence of solvents. However, the stamp album in soft file will be as well as easy to read all time. Robinson annulation may be useful for converting biomassderived compounds into jetfuelranged alkylcyclohexanes, but it has not been fully developed until now. The formation of a ring organic chemistry any reaction that forms a ring of atoms any structure in the form of a ringcancellation, revocation. Uci chem 125 advanced organic chemistry spring 2016 lec 22.
Draw the structure of the two neutral reactants required to form the product shown below. Enantioselective solvent free robinson annulation reactions. Amino acid salt catalyzed intramolecular robinson annulation. Reports on solventfree reactions have become increasingly frequent and the field has. Lets walk through the whole mechanism, using the simplified example of 2 propanone and methyl vinyl ketone. Request pdf enantioselective solventfree robinson annulation reactions the enantioselective cyclization of the prochiral cyclic substrates1 to7 and26, can be carried out in theneat using s.
The robinson annulation provides with a model reaction to evaluate the enantioselectivity in the research of. Introduction the robinson annulation is a useful reaction for the formation of sixmembered rings in polycyclic compounds, such as steroids. As is the case with robinson annulation, michael addition usually happens first to tether the two reactants together, then aldol. But this onepot fluorinationrobinson annulation only gave 3a in pdf. File type pdf organic chemistry smith 3rd edition solutions manual free. The danheiser benzannulation is a regiocontrolled phenol annulation. The robinson annulation reaction university of calgary. You may do so in any reasonable manner, but not in. While proline and its derivatives provided poor yields and ees, the combination of a catalytic amount of trifluoroacetic acid and a stoichiometric amount of prolinol tbs ether gave better results 79% ee.
Sep 28, 2009 in summary, an amino acid salt catalyzed intramolecular robinson annulation reaction has been developed, which provides a simple route to a tricyclic ring structure resembling the important antibiotic compound platencin. The robinson annulation is a useful reaction for the formation of sixmembered rings in polycyclic compounds, such as steroids. Directed epoxidation followed by selective epoxide opening furnished the final tetraol. A prolinecatalyzed asymmetric robinson annulation reaction tommy bui, carlos f.
The 1,4addition or conjugate addition of resonancestabilized carbanions. Mar 11, 2015 watch more of this topic at download this pdf. This feature is particularly attractive in the frame of an organic chemistry course. The robinson annulation is a ringforming reaction that combines a michael reaction with an intramolecular aldol reaction the two starting materials for a robinson annulation are an. In the following robinson annulation, compound a could be formed but is not a final product of the reaction. The simmons smith reaction in this video, i discuss how to form cyclopropane using an alkene, and the effect of stereochemistry on the reaction david. To acquire the baby book to read, as what your contacts do, you need to visit the colleague of the pdf lp page in this website. Enantioselective solventfree robinson annulation reactions.
The robinson annulation reaction chemistry libretexts. For more details on the named reactions please check. The stepbystep robinson annulation of chalcone and ethyl. Carbonyl condensations with enamines the stork reaction. Barbas, iii tetrahedron letters volume 41, issue 36, september 2000, pages 69516954 doi. An overview on the robinson annulation bentham science. Robinson annulation retrosynthesis reaction mechanism. The robinson annulation reaction university of calgary in. General characteristics the synthesis of naphthalene hydroquinones from phthalide anions and. The most common partners in the reaction are a nucleophilic donor such as a cyclic ketone, a bketo ester, an enamine, or a bdiketone and an unsaturated ketone acceptor. Aldol condensation, crotonization, claisen condensation, dieckmann condensation, reformatsky reaction, knoevenagel condensation, perkin condensation, mannich reaction, michael addition, robinson annulation.
This file is licensed under the creative commons attributionshare alike 3. Free download fundamentals of chemistry 5th edition by. The most common partners in the reaction are a nucleophilic donor such as a cyclic ketone, a bketo ester, an enamine, or a. The above mechanism, though demonstrated for the onestep process carried. In a second step the methyl group adjacent to the carbonyl is deprotonated and undergoes an. The robinson annulation is a threestep process involving a michael addition followed by an internal aldol condensation and a dehydration. This annulation provides an efficient route to form an aromatic ring in one step. These strategies can be used to create aromatic systems from acyclic precursors in a single step, with many substituents already in place. Mechanistically, robinson annulation is michael addition followed by intramolecular aldol condensation. It is a thermal combination of a substituted cyclobutenones with heterosubstituted acetylenes to produce highly substituted aromatic compounds, specifically phenols or resorcinols scheme 1. To do the retrosynthesis, remember to reverse the dehydration first, placing the hydroxyl on. 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. The method uses a ketone and a methyl vinyl ketone to form an. Enantioselective solventfree robinson annulation reactions indian.
Enantioselective solvent free robinson annulation reactions 199 2. It provides plenty of synthesis examples and practice problems. Organic chemistry smith 3rd edition solutions manual free. Herein, a strategy for the synthesis of highly branched c15 alkylcyclohexanes with lignocellulosederived furfural and 2,4pentanedione was developed with robinson annulation as the key step. In addition to these classical reactions, we recently discovered a new sequence of free radical and carbanionic reactions for the annulation of the cyclohexane ring involving carboncarbon bond formation. Instead a combination of sphenylalanine and dcamphorsulphonic acid was found to be effective in bringing about cyclization of trione 27 to s 30. Onepot fluorination and organocatalytic robinson annulation. The michael addition is thermodynamically controlled. A key robinson annulation allows for the building of the desired carbon framework in one highyielding step.
Under appropriate experimental conditions, it is possible to stop the reaction after every step and to isolate the three products separately. Carbonyl condensation reactions are widely used in synthesis and are the most versatile methods for synthesizing complex molecules. Robinson annulation reactions have a distinct place in synthetic organic. A number of six organocatalysts were screened for the asymmetric robinson annulation reaction of chalcone 6a and. A common synthetic annulation reaction is the robinson annulation. The robinson annulation involves two sequential re. By using silica gel as absorbent, this type of catalyst is readily recoverable and reusable. After the completion of the fluorination, chalcone 6a, cf 3 c 6 h 4 co 2 h and catalyst cat1 were added to the reaction mixture at 25 c for the robinson annulation. Draw the major product of the following robinson annulations reactions. We then started screening the optimal organocatalysts for converting compound 1 to the robinson annulation product 2. Robinson annulation or robinson annelation is a synthetic protocol used to construct cyclohexane rings. Conjugate addition, then intramolecular aldol and finally an elimination.
This video discusses the mechanism of the robinson annulation which involves the reaction of cyclohexanone with a michael acceptor such as. In this experiment, ethyl acetoacetate will react with transchalcone prepared in the experiment 4 to yield the product 6ethoxycarbonyl3,5diphenyl2cyclohexenone. Ring construction via annulation baran group meeting. The mechanism begins with deprotonation with the base of the. The robinson annulation is a combination of two carbonyl coupling reactions, the michael reaction and the intramolecular aldol condensation. This is the general description of the robinson annulation.
The robinson annulation is an organic reaction used to convert a ketone and an. Robinson annulation robinson annulation 1 draw the major. A complex sequence that can be used to form bicyclic systems containing a substituted cyclohexenone system. It is used frequently to synthesize polyketide compounds. The robinson annulation is the name for a process that combines two key reactions youve learned previously into one longer sequence. The robinson annulation reaction, which leads to formation of a substituted cyclohexanone, demonstrates the utility of a carbonyl condensation reaction. Explain why the michael reaction of 2phenylcyclohexanone with 2propenenitrile gives the product shown in the equation on page 894 rather than this product. The first step in the process is the michael addition to an. Robert robinson won the nobel prize for chemistry in 1947 for his contribution to the study of alkaloids.
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