Robinson annelation reaction

An intramolecular bicyclization reaction of the Robinson annelation-type has been reported as an extension of the aldol-type reaction (Eq. 12) [10]. The success of this multi-step reaction might be attributable to both the basicity and acidity of zirconium alkoxide. 

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The Robinson annelation reaction has classically been employed for the building up of the six-membered ring components of the steroid nucleus (18). In the original method, the enolate is treated with the methiodide of )9-diethylaminoethyl methyl... 

Ecologically and economically valuable solvent-free Robinson annelation reactions, which proceed efficiently in a one-pot process at room temperature, have been reported [ 10]. For example, 2-methylcyclohexanone (59), methyl vinyl... 

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,. <... 

WICHTERLE REACTION, Modification of the Robinson annellation reaction in which 1,3dichloro-ci,r-2-butene is used instead of methyl vinyl ketone... 

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). 

The forward synthetic sequence would therefore involve the Michael reaction of 2-methylcyclopentane-l,3-dione with methyl vinyl ketone to give (20), followed by cyclisation to the hydroxyketone (19), and then dehydration to the target molecule (13a). The overall process of addition and cyclisation is known as the Robinson annelation reaction.3 In this preparative example (Expt 7.6) the methyl vinyl ketone is used directly under conditions which minimise its polymerisation 48 it should be noted, however, that many literature examples of the annelation reaction use Mannich bases or the corresponding methiodides as an in situ source of the a, /J-unsaturated carbonyl component (see Section 5.18.2, p. 801). 

The indium trichloride-catalyzed Mukaiyama aldol reaction of 3-aminoketoesters with various silylenolethers gave under solvent-free conditions 1,3-amino alcohols with high stereoselectivity [36], Several Robinson annelation reactions have been carried out enantio-selectively using (S)-proline as a chiral catalyst [37]. Remarkably, the enantioselectivity was distinctly higher in the absence of solvent than in DMSO. 

To introduce the topic, an example. It may seem to you that any six-membered ring might show different chemical shifts for axial and equatorial groups. But this doesn t happen. Consider the result of this Robinson annelation reaction. 

EttdaUne sesquiterpenes. Syntheses of eudaicne-type sesquiterpenes commonly utilize the Robinson annelation reaction to construct the bicyclic ring system. However, this annelation reaction often proceeds in low yields and with stereochemical difficulties. Huffman and Mole have recently reported a new stereoselective synthesis. 8-Methoxy-tctralin-2-carboxylic acid (1) is reduced under Birch conditions followed by acid... 

In the synthesis of occidentalol (ref. 13), a eudesmane-type compound consisting of a cis-fused decalin containing a homoannular 1,3-diene system, dihydrocarvone was converted by a typical Robinson annellation reaction to the basic reguired bicyclic structural unit. (It is of interest that a related bicyclic methyldecalenone structure, the Wieland-Miescher ketone, has been employed for the synthesis of longifolene (ref.14), copaene (ref.15) and sativene (ref.16) by three totally different strategies outside the present concept of the semi-synthetic approach). 

Miyamoto, H., Kanetaka, S., Tanaka, K., Yoshizawa, K., Toyota, S., Toda, F. Solvent-free Robinson annelation reaction. Chem. Lett. 2000, 888-889. 

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. 

Annelation. Both Wenkert1 and Ireland3 have used this vinyl ketone in Robinson annelation reactions, for example ... 

Examples of intramolecular aldol reaction are legion, mainly in the context of the Robinson annelation reaction. Because this process has been the subject of recent reviews," we do not here attempt an exhaustive survey. Emphasis in this chapter is placed on representative examples, to show the scope of the reaction, and questions of regio- and stereo-selectivity. 

A tandem sulfide-contraction and Robinson annelation reaction was used for the synthesis of a me-sembrine analog, A -mesembrenone (133). The aryl-substituted thiobutyrolactam (130) was treated with chloromethyl vinyl ketone followed by diisopropylethylamine to afford A -mesembrenone (133) in good yield (Scheme 29). The reaction probably proceeds through initial sulfide contraction to the intermediate vinyl enaminone (131), which tautomerized to the enamine (132) and underwent intramolecular Michael closure to produce (133). 

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