Michael-type dimerization

An interesting Michael-type dimerization of cyclic enones (518) - (519) has been reported to proceed in the presence of a catalyst generated from Rh(cod)2Bp4 and the diene ligand (520) however, the enantioselectivity was rather low (25% ee) ... 

The numerous known flavin dimer species are reviewed in Table II. Apart from the normal very unstable quinhydrone 7r-complex (15, 16), which can only be observed in protic media, and apart from the stable biflavins obtained irreversibly by a Michael-type alkali-catalyzed selfcondensation of flavoquinone (22), there are two further types of o-dimers known besides the above one, namely the 7<, 4a-product of phosphate-catalyzed photodimerization (23) and the 5,5 -deazaflavin dimer (24), which is discussed below. 

A simple Michael-type addition of the methyl group of a monomer to the C=N bond of another molecule gives a dimer of type B2 e.g., dimers 72 and 73 are formed by the acid-catalyzed self-condensation of 2-hydroxy- (or 2-mercapto-)4-methyl-6-phenyl-1,6-dihydropyrimidine97... 

The Michael-type condensation of the side chain of a monomer with the nucleus of another molecule under basic conditions is exemplified by the dimer (84) formed when 2-aminoisoquinolinium picrate is passed through an anion-exchange column.108... 

Inspection of empirical formulas and the corresponding structures of starting material and product reveals that III is solely a dimer of I. Two important facts, however, conspire against this outer-layer simplicity. First, if the deep-blue compound I is allowed to dimerize by itself (and this in fact occurs in solution), the colorless dimeric structure IV (but not III) results. Second, there is an enamine in the medium, which obviously makes the difference. The role of this enamine should not be taken lightly, particularly if the conjugation of the sulfur atoms in I imbues this compound with a behavior reminiscent of oxygen homolog systems, that is, quinonoids. The exocyclic double bond is amenable to a Michael-type 1,4 addition by suitable nucleophiles while the thioketone sulfur is potentially a nucleophilic center (see Scheme 28.1). 

Figure 6.6 shows our synthetic plan for testudinariol A (149). Because the structural feature of target molecule 149 is its C2-symmetry, 149 can be obtained by dimerization or its equivalent operation of A. The intermediate A may be prepared from B by (Z)-selective installation of the two-carbon appendage. For the stereoselective construction of the cyclopentane portion of B, an intramolecular ene reaction is appropriate employing C as the substrate. The intramolecular oxy-Michael-type cyclization of D has been adopted to prepare the tetrahydropyran ring of C. The intermediate D can be synthesized from F [(R)-glycidol] via the known diol E. 

Figure 10.2 The catechol side chain of DOPA is capable of forming reversible interactions and irreversible covalent bonds. The benzene ring of the catechol is capable of n-n interactions (A). Catechol -OH groups can function both as a hydrogen bond donor and acceptor (B). Catechol forms strong coordination complexes with metal ions (C). When catechol is oxidized to form highly reactive quinone (D), it can undergo dimer formation (E) and subsequently polymerize into oligomers. Quinone can form intermolecular crosslinking with nucleophile such as -NH2 through Schiff base substitution (F) and Michael-type addition (G).

Bisdeoxyflavoskyrin (34), obtained by the Diels-Alder-type dimerization reaction of dihydrochrysophanol (46), was subjected to base treatment by keeping it in pyridine for three weeks with occasional warming. The solution turned yellow and showed a pale yellow fluorescence. Bisdeoxyrugulosin (47) was obtained in low yield (less than 10%). This conversion involves C-O bond cleavage followed by oxidation of the hydroquinone moiety and then Michael-type condensation between two monomeric moieties. The partially hydrogenated bisanthraquinone 48 is the direct substrate of the... 

The Diels-Alder-type dimerization of dihydroanthraquinone, successive oxidation, and Michael-type condensation exactly reproduced the reactions involved in the biosynthesis. The biomimetic synthesis of bisdeoxyrugulosin (47) has been accomplished by Yang et al (1976) (Scheme 14). 

Michael addition of the deprotonated substrate to unreacted substrate. The oligomerization reactions proceed with coulometric values less than one, smaller for the longer chain. This type of reaction takes place when 8a is reduced in dry MeCN. The oligomerization chain is short, and a double-bond-containing dimer isolated as the major product (>35%) [59]. The structures 10 and 11 have been suggested for the dimer [59,60], corresponding, respectively, to attack of the conjugate base of 8a by C-2 or C-4 (Scheme 4). 

To date, no known bisindole alkaloid has been shown to be only an artefact. In addition, no experimental evidence exists which undermines the assumption that bisindole alkaloids are actually formed from the completed monomeric partners. Support for this idea is derived from the kind of reactions apparently necessary to effect such dimerisations which are known biogenetic processes amine-aldehyde condensations, Mannich reactions, Michael additions, Friedel-Craft type condensations, Diels-Alder type processes, radical coupling etc. The observation that the skeletal distribution amongst monomeric alkaloids is reflected throughout the dimeric series lends further support. 

Nafion resins have been used not only for the opening of epoxides but also for their isomerization to aldehydes or ketones [137]. Various other rearrangements and isomerizations are catalyzed by this solid acid, in some cases with selectivities higher than those obtained with other solid catalysts [138-140]. Other reactions that have been studied include the Peterson methylenation of carbonyl compounds [141], hetero-Michael additions to unsaturated ketones [142], the Koch-type carbon-ylation of alcohols to form carboxylic acids [143], dimerization of a-methylstyrene [144], addition of carboxylic acids to olefins [145] and Diels-Alder reactions [146]. Notably, in most cases, reutilization of the catalyst is considered but only after an appropriate washing protocol to regenerate its acidity/activity. 

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