Mar 24, 2015 enantioselective robinsontype annulation reaction between. Mechanistically, robinson annulation is michael addition followed by intramolecular aldol condensation. I think many people have not been connecting the mechanisms with the overall reactions we have been discussing. Request pdf robinson annulation michael addition of cyclohexanones to methyl vinyl. Actually, the aldol reaction may be catalyzed by either acid or base, but base catalysis is more common. Carbonyl condensation reactions are widely used in synthesis and are the most versatile methods for synthesizing complex molecules. When you look at a mechanism, make sure you can explain exactly what every component of the reaction is doing. Organometallic intermediates intramolecular grignard reactions. Conjugate addition reactions factors that favour the process 5 since the conjugate addition is performed under protic. Ring construction via annulation baran group meeting. The robinson annulation reaction combines a ketone with an alpha beta unsaturated ketone to produce a 1,5 dicarbonyl compound which. The robinson annulation reaction, which leads to formation of a substituted cyclohexanone, demonstrates the utility of a carbonyl condensation reaction. When combined with a michael reaction it is called a robinson annulation, a key reaction used to make steroids. Jan 04, 2015 the robinson annulation is really neat, you guys.
Carbonyl condensation reaction o naoh o oh heat dehydration o aldol condensation o 1. Robinson annulation involves the following basic steps. Oct 31, 2016 key to the strategy is an organocatalyzed robinson annulation reaction of the nazarov reagent that affords chiral enone building blocks with high enantioselectivities. These products are important systems in various natural products, for example within steriods. One such application is called the robinson annulation. In these cases, the stereochemistry of the robinson annulation product reflects the fact that the initial combination occurred. Example michael addition the michael reaction is a useful method for forming carboncarbon bonds. Asymmetric synthesis of octahydroindoles via a domino. Depending on how the sequence is devised, the reaction can be terminated by either reductive elimination or. Robinson annulation is also used for synthesizing spirocyclic compounds.
Formation of olefins by basepromoted decomposition of ptoluenesulfonylhydrazones of aldehydes and ketones. Organic letters onecarbon bridge stereocontrol in robinson. All structured data from the file and property namespaces is available under the creative commons cc0 license. These bases can be generated from the reaction of hexamethyldisilazane with an appropriate base.
To our surprise, the robinson annulation reaction of ethyl acetoacetatewith2allyl2cyclohexenone11gave3b anti rather than 3a syn as the major product table 1, entry 1. The robinson annulation is useful only in simple cases, or where the availability of starting materials compensates for the low yield of desired product. Repeating the robinson annulation originally reported by kraus, we were also surprised to. The robinson annulation is an organic reaction used to convert a ketone and an. Carbonyl condensations with enamines the stork reaction 23. Enolates in organic synthesis bases for generation of enolates alternative nitrogenous bases that have attracted wide use include sodium hexamethyldisilazide nahmds or lithium hexamethyldisilazide lihmds.
Robinson annulationdirected synthesis of jetfuelranged. A straightforward, twostep asymmetric synthesis of octahydroindoles has been developed on the basis of two complementary strategies. The merits of the robinson annulation lie in its applicability in the total synthesis of. One of the many applications of robinson annulation is in the synthesis of estrone, a steroid hormone. The robinson annulation is a useful reaction for the formation of sixmembered rings in polycyclic compounds, such as steroids.
One route by which such a synthesis can be achieved is through the use of the robinson annulation reaction. Predict the product in the following michael reaction. The robinson annulation reaction chemistry libretexts. This reaction enabled the first synthesis of steroids. It was discovered by robert robinson in 1935 as a method to create a six membered ring by forming three new carboncarbon bonds. In biology, aldollike reactions are used to form and breakdown sugars. The robinson annulation provides with a model reaction to evaluate the enantioselectivity in the research of organocatalysis. When the product of a michael reaction is treated with naoh, h 2 o, and heat, a robinson annulation. In addition, the corresponding reaction involving a nitrogen atom is similarly called as the aza. Conjugate addition reactions university of nairobi. Reaction of the moreelectrophilic ketone group with ethylene glycol forms the ketal, expelling water. For the love of physics walter lewin may 16, 2011 duration.
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. C of carbonyls can act as a nucleophile in a number of. Its a michael addition followed by an intramolecular aldol condensation, and it makes a ring. This reaction, which may at first look very complex, can be readily understood once you realize that it simply involves a michael reaction followed by an intramolecular aldol condensation. Robinson annulation may be useful for converting biomassderived compounds into jetfuelranged alkylcyclohexanes, but it has not been fully developed until now. Carbonyl alpha substitution reactions alphasubstitution reactions occur at the position next to the carbonyl group the. Extra dielsalder practice problems ohio northern university. For some arrows, more than one step may be necessary. The mechanism begins with deprotonation with the base of the. Permuting dielsalder and robinson annulation stereopatterns. Sibi lecture 34 during the second world war, synthesis of steroids became very important. The robinson annulation is a chemical reaction used in organic chemistry for ring formation.
Antibodycatalyzed enantioselective robinson annulation. The first step in the process is the michael addition to an. Controlled isomerization of the double bond of certain dielsalder reaction products provides substrates that, upon oxidation, give rise to products whose gross structure corresponds to that of a robinson annulation. Cif file for 3o and copies of 1h and c nmr spectra and hplc traces. In fact, if the michael addition takes place under strongly basic conditions, the 1,5dicarbonyl is not isolated. Files are available under licenses specified on their description page. Michael reaction followed by aldol the product of a michael reaction, a 1,5 dicarbonyl, is often ideally suited to undergo an intramolecular aldol condensation. Predict the product of the following stork enamine reaction. Both of these steps involve attack by enolate anions. Robinson annulation or robinson annelation is a synthetic protocol used to construct cyclohexane rings.
Review of cc bond forming reactions chem 212 in an effort to summarize everything we have covered, this survey has been prepared. The robinson annulation provides with a model reaction to evaluate the enantioselectivity in the. Amino acid salt catalyzed intramolecular robinson annulation. H by an electrophile e through either an enol or enolate ion. Organic chemistry chemical society detailed mechanism american chemical. Ozonolysis of the alkene followed by reduction of the ozonide gives an aldehyde. The formation of unrearranged alkenes, generally the less substituted isomers, by treatment of ketone derived p. Nov 15, 2011 this page was last edited on 11 november 2016, at 14. The aldol reaction an important reaction of enolate anions is nucleophilic addition to the carbonyl group of another molecule of the same or different compoundclaisen condensation is but one example. Cascade reactions in which multiple insertion reactions take place are also possible. A prolinecatalyzed asymmetric robinson annulation reaction. Show full abstract total synthesis, aiming at schematizing achievements of the reaction. The quaternary carbon stereogenic center can direct the subsequent reactions and allow the rapid and diastereoconvergent assembly of complex decalines with contiguous stereocenters. Media in category robinson annulation the following 26 files are in this category, out of 26 total.
It is also useful in that the product of the reaction can undergo an intramolecular aldol condensation to form a sixmembered ring. Enantioselective solventfree robinson annulation reactions article in journal of chemical sciences 13. The robinson annulation reaction university of calgary. A complex sequence that can be used to form bicyclic systems containing a substituted cyclohexenone system. The reactions is typically low yielding due to polymerization of michael acceptor by strongly basic enolates. Mechanism, references and reaction samples of the stobbe condensation. Enantioselective solventfree robinson annulation reactions. Expedient and diastereodivergent assembly of terpenoid. The silica gel absorbed amino acid salt catalyzed asymmetric intramolecular robinson annulation reaction has been developed. Conjugate addition, then intramolecular aldol and finally an elimination. A number of chiral cyclohexenone derivatives containing an amide group. The aldol reaction has been very important in the synthesis of various pharmaceuticals and natural products. Robinson annulation 12 the robinson annulation generates a cyclohexenone ring on top of a preexisting ring thereby providing a 56 or 66 ring system. Asymmetric robinsontype annulation reaction between.
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