Michael addition nitrogen

Such groups a to a pyridine-like nitrogen atom are expected to undergo Michael additions. Examples are known in the imidazole series. 

BMI was also used as a crosslinking agent for poly(iminoethylene). The Michael addition takes place with the nucleophilic nitrogen of the imino group and the double bonds of the electrophilic BMI. The Michael addition of BMI is now adopted as a crosslinking reaction for polymers with amino end groups [2]. 

From a mechanistic standpoint, ammonia serves two functions 1) it behaves as a base to catalyze an aldol reaction between 2 equivalents of 31 to generate the corresponding enal 33, and 2) it is the source of nitrogen for the resultant pyridyl ring. This occurs through formation of enamine 34 with a third equivalent of 31. The Michael addition of 34 to 33 followed by cyclization gives rise to 32. 

The Michael addition of enamines to nitroalkenes proceeds with high Yyn selectivity. The Yyn selectivity is explained by an acyclic synclinal model, in which there is some favorable interaction between the nitro group and the nitrogen lone pair of the enamine group CEq. 4.67i. Both Z- and E-nitrostyrenes afford the same product in over 90% diastereoselecdvity. 

A sequence of straightforward functional group interconversions leads from 17 back to compound 20 via 18 and 19. In the synthetic direction, a base-induced intramolecular Michael addition reaction could create a new six-membered ring and two stereogenic centers. The transformation of intermediate 20 to 19 would likely be stereoselective substrate structural features inherent in 20 should control the stereochemical course of the intramolecular Michael addition reaction. Retrosynthetic disassembly of 20 by cleavage of the indicated bond provides precursors 21 and 22. In the forward sense, acylation of the nitrogen atom in 22 with the acid chloride 21 could afford amide 20. 

In the synthesis of N heterocycles, this technique also overcomes competitive retro Michael addition that lowers the yield of 1,4-adduct in the Michael addition of amines to nitro olefins. Thus, a toluene solution of nitro olefin 159 was treated with allylamine 160, EtgN, and TMSCI under nitrogen at ambient tern-... 

Lipases are the enzymes for which a number of examples of a promiscuous activity have been reported. Thus, in addition to their original activity comprising hydrolysis of lipids and, generally, catalysis of the hydrolysis or formation of carboxylic esters [107], lipases have been found to catalyze not only the carbon-nitrogen bond hydrolysis/formation (in this case, acting as proteases) but also the carbon-carbon bond-forming reactions. The first example of a lipase-catalyzed Michael addition to 2-(trifluoromethyl)propenoic acid was described as early as in 1986 [108]. Michael addition of secondary amines to acrylonitrile is up to 100-fold faster in the presence of various preparations of the hpase from Candida antariica (CAL-B) than in the absence of a biocatalyst (Scheme 5.20) [109]. 

Certain proteases, for example alkaline protease from Bacillus suhtilis, have also proven to be good catalysts for the Michael addition of nitrogen nucleophiles to a,/3-efhylenic compounds [118, 119]. 

The Bunce group disclosed a straightforward domino process for the construction of aryl-fused nitrogen heterocycles by employing a combination of a reduction and a Michael addition [20]. The transformation involves an initial Fe-mediated reduction of nitroarenes 7-38, furnishing an aniline which undergoes a subsequent... 

The Michael addition of a nitrogen-centered nucleophile to nitroalkenes affords compounds that may serve as precursors of vicinal diamines, since the nitro group can be reduced to an amino function by reduction. The very convenient method for the preparation of 1,2-diamines is developed by the addition of C-ethylhydroxylamines to nitroalkenes followed by reduction with H2 in the presence of Pd/C (Eq. 4.24).30... 

The titanated bislactim ethers of cyclo(L-Val-Gly-) are added to nitroalkenes with high diastereo-selectivity (Eq. 4.60).SOa Michael addition of lactam bearing (S)-2-( 1-ethyl-1-methoxypropyl) pyrrolidine as auxiliary on the lactam nitrogen to nitroalkenes proceeds with high selectivity (de >96%, ee >96%).80b... 

Tandem reduction-Michael addition using suitably substituted nitroarenes provides a general route to aryl-fused nitrogen heterocycles (Eq. 10.79).135... 

Stereoselective Michael additions of carbon-, nitrogen-, oxygen-, and sulfur-centered nucleophiles to 6,7-dehydro-5-oxoindolizidine have been reported <2006JOC6630>. 

In order to study the reactivity of the nitrogen atom in saccharidic OZT moieties Rollin and co-workers13,55 explored some standard reactions IV-acylation, IV-sulfonylation, IV-vinylsulfonylation by Michael addition, reductive elimination, conjugated addition and cycloaddition. 

Application of an organocatalytic domino Michael addition/intramolecular aldol condensation to the preparation of a series of important heterocycles has recently received much attention [158] with methods being disclosed for the preparation of benzopyrans [159-161], thiochromenes [162-164] and dihydroquinolidines [165, 166]. The reports all use similar conditions and the independent discovery of each of these reactions shows the robust nature of the central concept. A generalised catalytic cycle which defines the principles of these reports is outlined in Fig. 10. Formation of iminium ion 102 is followed by an intermolecular Michael addition of an oxygen, sulfur or nitrogen based nucleophile (103) to give an intermediate... 

The Michael additions to 1 - 3 of a large variety of carbon, nitrogen, oxygen, sulfur and selenium nucleophiles, as well as hydride, followed by inter- or intramolecular transformations of the chlorine substituent or/and the methoxy-carbonyl fragment, offer versatile synthetic approaches to a large variety of synthetically useful and important organic molecules. 

As synthetic steps, the Michael additions of nitrogen nucleophiles were followed by nucleophilic substitutions of the chlorine atom with a primary amine and, finally, alkylations of the then secondary amino group with various alkyl bromides were performed just as previously developed for the chloro ester 1-Me in solution (see, e.g. Schemes 25,27,36 etc.). With differently substituted pyra-zoles as Michael addends, different primary amines and alkyl bromides, combinatorial libraries consisting of 8, 24 and 84 compounds were thus successfully prepared in ca. 60% yield and proved by the LC-MS technique to contain all the individual compounds in about equal amounts (Scheme 80) [127]. 

A plausible mechanism for the ring expansion (Scheme 65) proceeds via an intermediate zwitterion A, resulting from Michael addition of the tertiary nitrogen to the alkyne. Cleavage of the C(l)-N bond occurs via formation of the six-membered transition state B in which a molecule of alcohol facilitates the Sn reaction. 

The 3(2ff)-benzofuranone 98 undergoes Michael addition with ( )-pent-3-en-2-one (100, Scheme 25) in the presence of sodium ethoxide to afford the adduct 101 as a mixture of two racemates. Cyclization to the 2-dibenzo-furanone 102 can be induced by boiling with dilute aqueous sodium hydroxide under nitrogen or to the aromatized compound 103 in the presence of air. The dechloro compound (104) has been synthesized from 99 by a... 

---