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