Michael-type cyclization

The type III PKS chalcone synthase (CHS) then catalyzes the sequential condensation of three molecules of malonyl-CoA with one CoA-ester moiety to yield chalcones. Subsequently, chalcone isomerase (CHI) catalyzes the stereospecific intramolecular cyclization (Michael-type addition) of chalcones to the corresponding... 

D. Further Reactions of the Initial Michael-Type Zwitterions 1. Direct Cyclization... 

Cacchi and Palmier (83T3373) investigated a new entry into the quinoline skeleton by palladium-catalyzed Michael-type reactions. They found that phenyl mercurial 134 was a useful intermediate for the synthesis of quinoline derivatives, and that by selecting the reaction conditions the oxidation level of the heterocyclic ring in the quinoline skeleton can be varied. On such example is shown in Scheme 16. PdCla-catalyzed coupling between organomercurial reagent 134 and enone 135 delivered adduct 136 which was subsequently cyclized to quinoline 137 under acidic conditions. 

Scheme 4 Access to various a,/ -unsaturated carbene complexes from alkynylcarbene complexes 23. A 1,3-Dipolar cycloaddition. B Diels-Alder reaction. C Ene reaction. D [2+2] Cycloaddition. E Michael-type addition followed by cyclization. F Michael-type additions...

Some heterocyclic amides, in principle similar to those described above, were shown to cyclize in a Michael type reaction to give anellated pyridones in excellent yield 1-1393... 

All of these reactions proceed in a similar pathway which involves the Michael type additions of enamines to nitroalkenes or addition of nitroalkanes to imines and cyclization. This process has been achieved by solid-phase variation (Scheme 10.2).14... 

Recently, a rhodium-catalyzed tandem cyclization has been reported with an arylboronic ester bearing a pendant Michael-type acceptor olefin and acetylenic65 or olefinic66 derivatives. This transformation proceeds in a water-containing medium as solvent and proton source. This catalyst system is optimized with electron-rich and bulky ligands to stabilize the rhodium intermediate and decrease the protonolysis of boron derivatives in a protic solvent. 

In the epoxidation process (Figure 4.4), the oxygen of the enone s carbonyl function first coordinates with the zinc atom. The ethylperoxy anion then attacks the (3-position, which constitutes a Michael-type addition. The subsequent cyclization gives the epoxy ketone and the zinc alkoxide. 

Michael-type radical cyclization." A short synthesis of 3-demethoxyerythra-tidinone (3) involves a Michael-type radical addition. Thus 1 on reaction with BujSnH (AIBN) affords 2 as a single isomer in 65% yield. This product is converted by a three-step sequence into 3. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

Cyclopropanation reactions of chloroalkanes with jt-deficient alkenes under basic phase-transfer catalysed conditions have been observed. Thus, for example, chloroacetic esters and chloroacetonitriles undergo Michael-type reactions with acrylic esters and acrylonitriles, the products of which cyclize to give cyclopropanes (see Section 6.4). 

Balme G, Bouyssi D, Monteiro N (2006) The Virtue of Michael-Type Addition Processes in the Design of Transition Metal-Promoted Cyclizative Cascade Reactions. 19 115-148 Barluenga J, Rodriguez F, Fanands FJ, Fldrez J (2004) Cycloaddition Reaction of Group 6 Fischer Carbene Complexes. 23 59-121 Basset J-M, see Candy J-P (2005) 16 151-210... 

In troponoid chemistry cine substitution occurs frequently. In many cases it can be explained by the intermediacy of dehydrotropolone species ( tro-polonyne ) as trapped, for example, by azides (Section II,A,3,h Scheme 34). An alternative mechanism may be a Michael-type addition followed by elimination. The intramolecular cyclizations depicted in Scheme 47 very likely proceed via Michael-type attack (73CRV293, p.351). 

Microwave irradiation, for 15-20 min under solvent-free conditions, promoted the regiospecific three-component one-step cyclocondensation of benzoylacetonitrile, an aromatic aldehyde, and aminopyrimidinones 460 to give 6-cyano-5,8-dihydropyrido[2,3-, pyrimidin-4(3/7)-ones 461 rather than the isomers 462. The formation of 461 proceeds via a Michael-type addition of C-5 in aminopyrimidine 460 to the activated double bond of the arylidene-benzoylacetonitrile intermediate followed by cyclization with the removal of a water molecule. Compounds 461 were also prepared conventionally by refluxing the reactants in absolute ethanol for 40 8 h <2001TL5625>. 

The action of anions on 4-(chloromethyl)-l,4-dihydropyridines provides a useful route to 4//-azepines (Section 5.16.4.2.3). However, in several instances the 4,5-dihydro-4//-azepines (170) suffer further cyclization to the 2,5-bridged azepines (171 X=NH, NMe, NCH2Ph, S, Se) via an intramolecular Michael type addition at the 2,3-double bond (68JCS(C)23ii, 79CJC44). Occasionally, e.g. (170 X = p-MeC6H4S), the 4,5-dihydroazepine can be isolated. 

The reaction of the 2-pyridylvinyl ketone 28 with DMAD could take place in several ways, but nucleophilic attack from the nitrogen and Michael-type addition to the conjugated system gives the indolizine 30.251 A similar cyclization occurs with the diethyl malonate derivative 29 yielding 31, but in the case of 32 an unexpected rearrangement... 

A Pd-catalyzed Michael-type cyclization (Equation 21) is described as a method for construction of a substituted oxepan system <1999TL1747>. 

Refluxing of dihydroazoloazines and a,(3-unsaturated ketones in a methanol solution of sodium methoxide proceeds in a Michael-type addition. For example, reaction of 2-methyl-5,7-diaryl-6,7-dihydropyrazolo[l,5- ]pyrimidine 387 and chalcone 5 under these conditions yields adduct 388 [297] (Scheme 3.102). Treatment of 2-methyl-substututed triazolopyrimidine 389 with ketone 5 leads to cyclization with formation of the triazolo[5,l-Z ]quinazoline moiety [324]. 

Michael-type addition of a suitable nucleophile, e.g. thiols, on to the a,f)-unsaturated lactone. Such alkylation reactions are believed to explain biological activity, and, indeed, activity is typically lost if either the double bond or the carbonyl group is chemically reduced. In some structures, additional electrophilic centres offer further scope for alkylation reactions. In parthenolide (Figure 5.31), an electrophilic epoxide group is also present, allowing transannular cyclization and generation of a... 

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