Michael addition products

Stabilizing the resulting enolate of the Michael Addition product can shift the equilibrium as in the case of the vinyl silane shown below... 

Oxidative dimerization of various 2-benzyloxy-2-thiazoline-5-ones (222) catalyzed by iodine and triethylamine is another example of the nucleophilic reactivity of the C-4 atom (469) (Scheme 112). Treatment of 212 with pyrrolidinocyclohexene yields the amide (223) (Scheme 113). The mechanism given for the formation of 223 is proposed by analogy with the reactivitx of oxazolones with enamines (4701. 4-Substituted 2-phenylthiazol-5(4Hi-ones react with A -morphoiino-l-cyclohexene in a similar manner (562j. Recently. Barret and Walker have studied the Michael addition products... 

In a similar manner, overnight refluxing of 1-methyl-1,2,5,6-tetrahydropyridine-3-carbonitrile (112) with p-chlorothiophenol (108) at 100°C gave a Michael addition product as a 1 1 mixture of two isomers 113a and 113b in 70% total yield (Fig. 3). However, if the reaction was carried out at low temperature for 4 hours, kinetic isomer 113a was detected in 50% yield (84JHC981). 

Pyrazo[l,5-a]quinolines were synthesized by reaction of acrylates with 1-(Af-methylamino)quinolines 430 to afford the corresponding Michael addition product 431 which upon dehydrogenation with DDQ gave 432. 

Various competitive reactions can reduce the yield of the desired Michael-addition product. An important side-reaction is the 1,2-addition of the enolate to the C=0 double bond (see aldol reaction, Knoevenagel reaction), especially with a ,/3-unsaturated aldehydes, the 1,2-addition product may be formed preferentially, rather than the 1,4-addition product. Generally the 1,2-addition is a kinetically favored and reversible process. At higher temperatures, the thermodynamically favored 1,4-addition products are obtained. 

Problem 23.22 How would you prepare the following compound using a Robinson annulation reaction between a jS-diketone and an, /3-unsaturated ketone Draw the structures of both reactants and the intermediate Michael addition product. 

Vinyl sulfones, being good Michael acceptors, have been regarded as useful reagents for carbon-carbon bond formation. Nucleophiles used often are organometallic reagents, enamines and enolate anions and the Michael addition products are usually obtained in... 

In this chapter, we have described some useful properties of coordinated QM complexes. For instance, remarkably stable T 2-o-QM complexes of Os can release the QM moiety upon oxidation, followed by controlled reaction with suitable dienophiles to form the chroman ring system.15 16 ri2-Coordinatedp-QM complexes can be easily released upon exposure to an electron-deficient alkene and trapped as the 1,6-Michael addition product.18 19... 

SCHEME 10.1 Resonance structures of a simple p-QM and the Michael addition product with nucleophile XH. 

The Michael addition products 28-a and 28-b can be reketalized under Lewis acidic conditions to form 29-a and 29-b which presumably further eliminate methanol to aromatize to form the target 30. 

In a related example, reaction of N-hydroxy-N-methylthiophene-2-carboximidamide 56 with DMAD gave a double Michael addition product 57, which when heated at reflux in xylenes, afforded hydroxypyrimidinone 60 in 57% overall yield (Scheme 6.21) [9f]. The mechanism invoked was opening of the oxa-diazole 57 to 58, followed by a [3,3]-Claisen-type rearrangement to 59, which, after tautomerization and cyclization, afforded 60. 

Amino-substituted dienes are also important dienophiles in Diels-Alder reactions. Recently, chiral and achiral 2-amino-l,3-dienes have been prepared to study their reactivity (see also asymmetric Diels-Alder reaction Section 8.1.2). The reaction of 2,3-diamino-l,3-butadienes with nitrostyrene gives unusual [3+2]carbocyclization products, 2-aminocyclopentanones, which are not formed by the direct cycloaddition but derived from the Michael addition products (see section discussing the Michael addition Section 4.1.3).42... 

Reactions of a,(3-unsaturated acylzirconocene chlorides with stable carbon nucleophiles (sodium salts of dimethyl malonate and malononitrile) at 0°C in THF afford the Michael addition products in good yields (Scheme 5.38). Direct treatment of the reaction mixture with allyl bromide in the presence of a catalytic amount of Cul -2LiCl (10 mol%) in THF at 0 °C gives the allylic ketone in a one-pot reaction. This sequential transformation implies the electronic nature of a,P-unsaturated acylzirconocene chloride to be of type E as shown in Scheme 5.37. 

Superoxide anion formed in situ in a solution exposed to air (i.e. with only a small concentration of O2) has been used as an EGB to generate nitroalkane anions that may add to activated alkenes or to carbonyl compounds [130, 131]. An example is shown in Scheme 33. The reaction is catalytic since the product anion can act as a base toward the nitroalkane. Using the nitroalkane as the solvent favors the proton transfer pathway over the competing addition of the product anion to a second molecule of activated alkene, a pathway that may lead to polymerization [130]. In some cases, better yields of the Michael addition product were obtained if a stoichiometric amount of the anion was formed ex situ (with O2 as the PB), and the activated alkene added subsequently ]130, 132]. 

When cyclic enones were used as Michael acceptors, both malonates and acetoacetates gave impressive yields and enantioselectivities of the desired Michael addition products (Scheme 5.2Q) NMR spectra and single-crystal X-ray data supported the following ruthenium intermediate (Scheme 5.21) and transition state (Figure 5.8). 

When nitroalkenes were used as Michael acceptors, high yields and enantioselectivities of the desired Michael addition products were also obtained (Scheme 5.22). In these reactions, a well-defined chiral Ru amido complex (Figure 5.9) was an efficient catalyst. The mild reaction conditions and high reactivities and stereoselectivities allowed a large-scale reaction in the presence 1 mol% Ru catalyst. By using a chiral Pd(II) catalyst, an asymmetric allylic arylation was reported by Mikami and coworkers to give the cross-couphng product via the activation of both allylic C H and aryl C H bonds in moderate enantioselectivity (Scheme 5.23). ... 

Sharma and Degani have used 2-hydroxyethylammonium formate as a low cost alternative to imidazolium based ILs in hetero-Michael reactions. They have synthesized many Michael addition products containing C-N... 

An attempt to introduce a bulky triphenylmethyl substituent at N-(y of methyl 677-furo[2,3-7]pyrrole-5-carboxylate 31a led to C-2 triphenylmethyl substitution giving the product 157, which with ethyl propynoate in acetonitrile gave the Michael addition product 158 <2000PJC207> (Scheme 16). 

Condensation polymers consisting of the Michael addition product of ami-noethylpiperazine with 1,4-butanediacrylate, (I), as illustrated in Eq. (2) were prepared by Liu et al. (2) and used as vectors for delivery of DNA (deoxyribonucleic acid) to a cell. 

Recently, lithiodifluoromethylphosphonate was reacted with methyl vinyl ketone followed by rearrangement of the allylic alcohol to give the difluoromethylphosphonate derivative as the E isomer [263] (Scheme 89). This lithium reagent was also reacted with nitroalkenes in the presence of CeCl3 to produce the corresponding Michael addition products in moderate yield [264] (Scheme 90). 

Fig. IS. Michael addition product of BMI with aromatic diamine...

Bicyclic bridged phosphorinane derivatives can be synthesized by different methods. When phenylphosphine is heated with cycloocta-2,7-dienone to 135 °C in the presence of polymerization inhibitors, e.g. hydroquinone, and the double Michael addition product is oxidized, the two crystalline syn and anti isomers (total yield 48-59%) are isolated. Separation by crystallization gives the pure compounds which can in turn be transformed at the carbonyl or the phosphorus group (equation 10) (75T33,76JOC589). 

Pyrrole and 1-alkylpyrroles generally react with ir-deficient alkenes and alkynes to give Michael addition products (see Section 3.05.1.2.6), but Diels and Alder (3lLA(490)267) reported that 1-methylpyrrole also gave a 1 2 adduct with DM AD formulated as (229), which could be derived from a [w4+w2] cycloaddition of a second molecule of DM AD with the initially formed Michael adduct (cf. Section 3.05.2.3). Subsequent work, however, has shown structure (229) for the 1 2 adduct to be incorrect, the true structure being (230) (63AHC(i)i25, 78AHC(23)265). The formation of the dihydroindole (230) requires the initial... 

Methyl perfluoromethacrylate reacts with allyl and propargyl alcohols to give the Michael addition products 19 and 20, respectively these eliminate hydrogen fluoride in the presence of the boron trifluoride-triethylamine complex and rearrange to acyl fluorides 21 and 22. Hydrolysis of the acyl fluorides with base results in decarboxylation to give the 2-(trifluoromethyl) esters 23 and 24.11... 

Michael addition products, the ethoxycyclopropyl analogue gave also the allenyli-denechromium complex resulting from the elimination of ethanol. 

---