Nitroolefins Michael addition

Some particular features should be mentioned. Instead of Michael additions, a-nitroolefins are reported to yield allyl sulfones under Pd catalysis (equation 21). Halogenated acceptor-olefins can substitute halogen P to the acceptor by ipso-substitution with sulfinate (equation 22 , equation 23 ) or can lose halogen a to the acceptor in the course of a secondary elimination occurring P to the introduced sulfonyl groups (equation 24). On the other hand, the use of hydrated sodium sulfinates can lead to cleavage at the C=C double bond (equation 25). 

Addition of the lithium salt of tris(triphenylthio)methane to the D-glyceraldehyde-derived nitroolefin 80 resulted in a stereoselective Michael addition leading to adduct 81, which was then converted into the novel... 

Another recent example of a Michael addition of organometallic reagents to sugar nitroolefins consists of the addition of vinyl magnesium bromide to nitroolefin 83, that afforded nitro sugar 84 (Scheme 27).64... 

A Michael addition-Nef reaction sequence was used in a synthesis of disaccharides. Addition of the sodium salt of 1-thio-D-glucose to sugar nitroolefin 112 gave a mixture of isomers 113. The subsequent deacetylation, followed by a Nef reaction, afforded the S -disaccharides 114 and 115 (Scheme 35).82... 

Recently, a synthesis of tetrodotoxin from D-glucose was described (Scheme 36). After a Michael addition of the lithium salt of bis(phenylthio)-methane to the nitroolefin 116, the major component (117b) of the resulting epimeric mixture 117a + 117b was subjected to a reaction sequence that involved an intramolecular nitroaldol reaction, to give the complex nitro cyclohexane derivative 118. 

In general, copper-zinc compounds, unlike organolithium-derived organocopper reagents, undergo clean addition reactions to nitroolefins. After Michael addition, the resulting zinc nitronates can be oxidatively converted into polyfunctional ketones, such as 117 (Scheme 2.45) [96]. 

For Michael addition to nitroolefins, the lithio or titanium derivatives have been found to be useful [87AG(E)480], Hydrolysis gives a-amino--y-nitrocarboxylate esters (Scheme 69). 

Based on this gathered experience the diastereoselective alkylation of enantio-pure a-lithiated sulfonates was extended to the Michael addition with aliphatic nitroolefins [95]. Thus the Michael adducts 118 could be achieved in excellent yields (84-99%) with high diastereoselectivities de of 80-88% (84 to >98% after recrystallization or chromatography). Cleavage of the chiral auxiliary and treatment with diazomethane furnished the anti-configured a,j3-disubstituted y-nitro-methyl sulfonates 119 in overall yields of 41-70% and with excellent de- and ee-values (Scheme 1.1.32). 

J.-M. Lassaletta and R. FemSndez, Michael addition of formaldehyde dimethyl-hydrazone to nitroolefins. A new formyl anion equivalent, Tetrahedron Lett. 33 3691 (1992). 

The enantioselective aldol and Michael additions of achiral enolates with achiral nitroolefins and achiral aldehydes, in the presence of chiral lithium amides and amines, was recently reviewed354. The amides and amines are auxiliary molecules which are released on work-up (equation 90 shows an example of such a reaction). 

N-terminal L-proline, again in DMSO as solvent [40], In this study the maximum ee in the addition of acetone to trans-2-nitrostyrene was 31%. Alexakis and Andrey successfully employed the bis-pyrrolidine 52 as catalyst for the addition of aldehydes and ketones to trans-fi-nitrostyrene [41], whereas Barbas and Betancort [42] were able to perform the Michael addition of unprotected aldehydes to nitroolefins using the pyrrolidine derivative 53 as catalyst (Scheme 4.24). 

Several iodine-catalyzed organic transformations have been reported. Iodine-catalyzed reactions are acid-induced processes. Molecular iodine has received considerable attention because it is an inexpensive, nontoxic and readily available catalyst for various organic transformations under mild and convenient conditions. Michael additions of indoles with unsaturated ketones were achieved in the presence of catalytic amounts of iodine under both solvent-free conditions and in anhydrous EtOH (Scheme 19) [85,86]. l2-catalyzed Michael addition of indole and pyrrole to nitroolefins was also reported (Scheme 20) [87]. 

Aluminum salen complexes have been identified as effective catalysts for asymmetric conjugate addition reactions of indoles [113-115]. The chiral Al(salen)Cl complex 128, which is commercially available, in the presence of additives such as aniline, pyridine and 2,6-lutidine, effectively catalyzed the enantioselective Michael-type addition of indoles to ( )-arylcrolyl ketones [115]. Interestingly, this catalyst system was used for the stereoselective Michael addition of indoles to aromatic nitroolefins in moderate enantiose-lectivity (Scheme 36). The Michael addition product 130 was easily reduced to the optically active tryptamine 131 with lithium aluminum hydride and without racemization during the process. This process provides a valuable protocol for the production of potential biologically active, enantiomerically enriched tryptamine precursors [116]. 

Scheme 2.48 The Michael addition of aldehydes on nitroolefins, catalyzed by 45a and 45b.

Modified cinchona alkaloids 18 and 19, derived from quinine and quinidine, respectively, were utilized by Deng and co-workers for the catalytic asymmetric Michael additions of malonates to nitroolefins [49]. These catalysts effectively promoted the conjugate additions of methylmalonate to a variety of aromatic (90-99% yield 96-98% ee), heteroaromatic (97-99% yield 96-98% ee) and aliphatic (71-86% yield 94% ee) -substituted nitroolefins (Table 6.7). As the two alkaloids... 

Thiourea-Mediated Michael Addition of Ketones to Nitroolefins [29] (pp. 82-83)... 

Enaminones react98 with alkoxymethylene compounds derived from 1,3-dicarbonyl derivatives according to Bottorf and coworkers99 to give substituted pyridines as a result of Michael addition of the enaminone nitrogen (equation 68). Similarly, nitroolefines can be condensed with enaminone derivatives to give 3-nitropyridine derivatives100 (equation 69). 

Diketones y-keto esters. TiCU or SnCl4 activates nitroolefins for Michael addition with silyl enol ethers to form intermediate silyl nitronates, which are hydrolyzed to 1,4-diketones. 

Cao CL, Ye MC, Sun XL, Tang Y (2006) Pyrrohdine-thiourea as a bifunctional organocatalyst Highly enantioselective michael addition of cyclohexanone to nitroolefins. Org Lett 8 2901... 

The epi-quinine urea 81b was also found by Wennemers to promote an asymmetric decarboxylation/Michael addition between thioester 143 and 124 to afford the product 144 in good yield and high enantioselectivity (up to 90% ee) (Scheme 9.49). Here, malonic acid half-thioesters serve as a thioester enolate (i.e., enolate Michael donors). This reaction mimics the polyketide synthase-catalyzed decarboxylative acylation reactions of CoA-bound malonic acid half-thiesters in the biosynthesis of fatty adds and polyketides. The authors suggested, analogously with the enzyme system, that the urea moiety is responsible for activating the deprotonated malonic add half-thioesters that, upon decarboxylation, read with the nitroolefin electrophile simultaneously activated by the protonated quinuclidine moiety (Figure 9.5) [42]. 

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