Robinson condensation reaction

Scheme 2.1 Robinson condensation reaction catalysed by a combination of L-proline and (—)-spartein.

While mechanistically this reaction is related to the Robinson-Schopf reaction for the generation of the tropinone skeleton, it also has similarities to the Hantzsch reaction. Here the heterocyclic ring 75 is assembled by the condensation of an equivalent of acetonedicarboxylic ester 72 with 2 equivalents of aldehyde 73 in the presence of ammonia or primary amine 74. 

Davis and co-workers have carried out the first examples of the Knoevenagel condensation and Robinson annulation reactions [61] in the ionic liquid [HMIM][PFg] (HMIM = l-hexyl-3-methylimidazolium) (Scheme 5.1-33). The Knoevenagel condensation involved the treatment of propane-1,3-dinitrile with a base (glycine) to generate an anion. This anion added to benzaldehyde and, after loss of a water molecule, gave l,l-dicyano-2-phenylethene. The product was separated from the ionic liquid by extraction with toluene. 

Carbonyl condensation reactions are perhaps the most versatile methods available for synthesizing complex molecules. By putting a few fundamental reactions together in the proper sequence, some remarkably useful transformations can be carried out. One such example is the Robinson annulation reaction for tire synthesis of polycyclic molecules. The word annulation comes from the Latin annulus, meaning "ring," so an annulation reaction builds a new ring onto a molecule. 

Carbonyl condensation reactions are widely used in synthesis. One example of their versatility is the Robinson anuulation reaction, which leads to the formation of an substituted cyclohexenone. Treatment of a /3-diketone or /3-keto ester with an a,/3-unsaturated ketone leads first to a Michael addition, which is followed by intramolecular aldol cyclization. Condensation reactions are also used widely in nature for the biosynthesis of such molecules as fats and steroids. 

One-pot syntheses of diaryl-a-tetralones by Michael condensation and subsequent Robinson annulation reactions of isophorone with chalcones were performed efficiently in a solvent-free PTC system under the action of MW irradiation. Compared with conventional heating substantial rate enhancements were observed, within very short reaction times, by use of microwaves (Eq. 59 and Tab. 5.31). They were far better than those achieved by the classical method (NaOEt in EtOH under reflux for 24 h 40-56%). 

Robinson, Robert, and Gertrude M. Robinson. "Researches on Pseudo-Bases. Pt. II. Note on some Berberine Derivatives and Remarks on the Mechanism of the Condensation Reactions of Pseudo-Bases," JCS 111 (1917) ... 

Since the early contributions of Willstatter and Robinson, several alternative approaches following mainly two routes have been considered for synthesis of anthocyanins.One of the routes includes condensation reactions of 2-hydroxybenzaldehydes with acetophenones, while the other uses transformations of anthocyanidin-related compounds like flavonols, flavanones, and dihydroflavonols to yield flavylium salts. The urge for plausible sequences of biosynthetic significance has sometimes motivated this latter approach. In the period of this review, new synthetically approaches in the field have also predominantly been following the same general routes however, some new features have been shown in synthesis of pyranoanthocyanidins. 

Problem 17.49 The Robinson annelation reaction for synthesizing fused rings uses Michael addition followed by intramolecular aldol condensation. Illustrate with cyclohexanone and methyl vinyl ketone, CHj=CHCOCH,. <... 

Aldol reactions are often used to close five- and six-membered rings. Because of the favorable entropy (p. 211), such ring closures generally take place with ease, even where a ketone condenses with a ketone. An important example is the Robinson annulation reaction which has often been used in the synthesis of steroids and terpenes. In this reaction a cyclic ketone is converted to another cyclic ketone, with one additional six-membered ring containing a double bond. The substrate is treated with methyl vinyl ketone (or a simple derivative of methyl vinyl ketone) and a base.551 The enolate ion of the substrate adds to the methyl vinyl ketone in a Michael reaction (5-17) to give a diketone that undergoes or... 

The forward synthetic reaction is a base-catalysed condensation reaction between two carbonyl compounds, the aldol condensation leading to -hydroxy-aldehydes or / -hydroxyketones followed by dehydration. This sequence is one of the most important carbon-carbon bond forming reactions, and aldol-type condensation reactions are considered in a number of other sections of the text, for example, the Doebner reaction (Section 5.18.3, p. 805), the Knoevenagel reaction (Section 5.11.6, p. 681), the Perkin reaction (Section 6.12.3, p. 1036) and the Robinson annelation reaction (Section 7.2). 

Fig. 13.71. Tandem reaction I, consisting of a Michael addition and an aldol condensation Robinson annulation reaction for the synthesis of six-membered rings that are condensed to an existing ring.

Moving from rearrangements, condensation reactions were also presented. Condensation reactions occur when two reactive species condense with one another forming a new compound. The first was the aldol condensation (Scheme 8.9). Later, a more complex application of the aldol condensation was presented in the form of the Robinson annula-tion (Scheme 8.10). For both of these reactions, the underlying lessons relate to the ability to induce reactions and incorporate substitutions at carbon atoms adjacent to carbonyl groups. Similar reactivities of such carbon atoms can be utilized for alkylation (SN2) and acylation (addition-elimination) reactions as illustrated in Scheme 8.11. 

The Robinson annulation reaction combines a Michael reaction with an intramolecular aldol condensation to synthesize substituted ring systems. 

Carbonyl Condensation Reactions in Synthesis The Robinson Annulation Reaction... 

The intramolecular aidol condensation is a powerful tool for obtaining five- and six-member rings. This is an important step in the Robinson annulation reaction (see Section 7.9). 

When an a,P-unsaturated carbonyl compound is treated with a carbanion, particularly one that is stabilised by a carbonyl group as well, the resultant 1,4-addition with the formation of a new carbon/carbon bond is called the Michael reaction. Like the Claisen condensation, it is possible for this reaction to occur in an intramolecular manner with a suitably substituted compound. This reaction leads to the formation of a new ring and is called the Robinson annulation reaction. Write down the complete reaction sequence for the reaction between cyclohexanone and but-l-en-3-one. 

Robinson annellation reaction. Formation of six-membered-ring ,(i-iinsaturatcd ketones by condensation of cyclohexanones with methyl vinyl ketone or its equivalents, followed by an intramolecular aldol condensation. 

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