And Robinson annulation

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. 

As already discussed for aldol and Robinson annulation reactions, proline is also a catalyst for enantioselective Mannich reactions. Proline effectively catalyzes the reactions of aldehydes such as 3-methylbutanal and hexanal with /V-arylimines of ethyl glyoxalate.196 These reactions show 2,3-syn selectivity, although the products with small alkyl groups tend to isomerize to the anti isomer. 

These a,/l-unsaturated ketones and aldehydes are used as reactants in Michael additions (Section 1.10) and Robinson annulations (Section 2.1.4), as well as in a number of other reactions that we will encounter later. Entries 8 and 9 in Scheme 2.11 illustrate Michael reactions carried out by in situ generation of a,/ -unsaturated carbonyl compounds from Mannich bases. 

Trisubstituted six-member carbocycles were also prepared. Condensation of LI with commercial acetoacetanUides 9.14a-f produced, by one-pot Michael addition and Robinson annulation, the cyclohexenone library L4 (7680 members. Fig. 9.11). Noncommercial acetoacetamides Mi, prepared by condensation of diketene 9.15 with 40 primary and secondary amines (structures not shown in the paper), were used as monomers and condensed with a 320-member LI subset to give the expanded cyclohexenone library L5 (12,800 members). Difficulties in preparing extremely large discrete libraries, even using fuUy automated robotic workstations, and the need to diversify the screening set obliged the authors to limit the number of monomers and chalcones for any specific library/scaffold (see also LIO below). 

Olsen, R. S., Fataftah, Z. A., Rathke, M. W. Convenient procedure for carboxylation and Robinson annulations of ketones using triethylamine in the presence of magnesium chloride. Synth. Commun. 1986, 16, 1133-1139. 

There is a report on the synthesis of ( )-mesembrine (387) by a reaction involving aryl rearrangement and Robinson annulation through an enamine (191) (Scheme 46). Reaction of 3-bromo-N-methoxycarbonyl-... 

Antibodies 38C2 and 33F12 also catalyzed intramolecular aldol reactions and Robinson annulation (Scheme 6.4) 1,5-diketones 28 and 30 were converted into 29 and 31, respectively [15]. To explore the scope of Baldwin s rules in antibody-catalyzed intramolecular aldol reactions, 38C2 was incubated with three different aliphatic diketones - 2,4-hexanedione, 2,5-heptanedione and 2,6-octanedione. No catalysis was observed in the... 

CONJUGATE ADDITIONS OF ENOLATE IONS MICHAEL ADDITION AND ROBINSON ANNULATION... 

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