Nitroalkenes, Michael reaction with

Professor Seebach and coworkers (96) used silyl enolate (203) containing an additional C,C double bond in the Michael reaction with a-nitroalkene (204) in the presence of chiral LA (Scheme 3.146). 

The reaction involves the amine-catalyzed conversion of an aldehyde into a nitroalkene by reaction with nitromethane followed by a transition-metal-catalyzed Michael addition of p-dicarbonyl compounds in the same reaction vessel. Typically, amine catalysts and nickel complexes are incompatible due to their tendency to chelate and to render each other inactive. However, microencapsulation of poly(ethyleneimine) (PEI) forms catalyst 140, which can successfully be used in tandem with the nickel-based catalyst 141 (Figure 3.6). 

Acetylacetone has also been the subject of several studies when used as 1,3-dicarbonyl compound suitable to engage in a Michael reaction with nitroalkenes under H-bonding catalysis. In this context, Takemoto s catalyst 68a and valine-derived thiourea 74 have been tested in the reaction with acetylacetone with nitrostyrene furnishing good results, although no extensive study was carried out in order to evaluate the substrate scope with regard to the substitution at the nitroalkene. On the other hand, several functionalized thioureas have been expressly surveyed in this reaction, providing a detailed study... 

Amorphous SA treated with 3-aminopropyltriethoxysilane (tertiary amine) and 3-(diethylamino) propyltrimethoxysilane (primary amine) acts as a heterogeneous catalyst for the one-pot synthesis of 1,3-dinitroalkanes from aldehydes and nitromethane (Scheme 6.21) [133]. Trifunctionality of the catalyst surface has been proposed. Aldehydes are activated by surface acid sites and they react with secondary amino group to form imine intermediates. The proton of nitromethane is abstracted by a tertiary amine group accompanied by nucleophilic attack of the deprotonated nitromethane on the imine, which is also assisted by a surface acid site, resulting in nitroalkenes. Another nitromethane is activated by the tertiary amine group, and the Michael reaction with nitroalkenes occurs to give the 1,3-dinitroalkanes. 

The combination of an imine derived from the reaction of acrolein organocatalyst 1 with simple indoles 84 and nitroalkenes 85 affords the 3-(cyclohexenylmethyl)-indoles 86 (Scheme 7.16) [59]. In this reaction, the indole 84 initiates the Friedel-Crafts-type reaction followed by a Michael reaction with nitroalkenes 85 to the intermediate 87. From this process, a hydrolysis takes place and the resulting compound enters another catalytic cycle involving a Michael/aldol condensation reaction similar to those reported previously. 

Despite the fact that extensive studies have been conducted on secondary-amine-catalyzed Michael addition of unmodified a-monosubstituted aldehydes, there are few reports on the use of a,a-disubstimted aldehydes as nucleophiles, probably due to the high hinderance during the formation of enamine intermediates. By using (5)-l-(2-pyrrolidinylmethyl)pyrrolidme/TFA salt 19 as catalyst, Barbas and co-workers [13] reported the first application of a,a-disubstituted aldehydes in the enantiose-lective Michael reactions with nitroalkenes (Scheme 5.6). The corresponding Michael adducts bearing an all-carbon quaternary stereocenter were obtained in moderate diastereoselectivities and with moderate to good enantioselectivities (up to 91%). 

Penta-coordinated stannates undergo the Michael reaction with enones and nitroalkenes or cyanoalkenes due to the high nucleophilicity (Schemes 3-201, 3-202, and 3-203). This strategy is applicable to ketene stannyl acetals, which are less reactive than ketene silyl acetals due possibly to the easy equilibrium between 0-Sn and C-Sn tautomers, the C-Sn tautomers being predominating at temperatures above 0 Normally, Qf-stannyl esters are much less reactive with electrophiles. However,... 

The direct aziridinadon of nitroalkanes has been repotted for the first dme. Treatment of nitroalkene with an excess of CaO and NsONHCO-.Et fNs =4-nitroben2enesulfonyl gives the ct-nitroaziridine in good yields fEq. 10.70. ° The reaction proceeds via aza-Michael reaction followed by a ring closure. 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

The Michael addition of lithium enolates to nitroalkenes followed by reaction with acetic anhydride gives acetic nitronic anhydrides, which are good precursors for 1,4-diketones, pyrroles, and pyrrolidines (Eq. 10.73).113... 

In the presence of thiourea catalyst 122, the authors converted various (hetero) aromatic and aliphatic trons-P-nitroalkenes with dimethyl malonate to the desired (S)-configured Michael adducts 1-8. The reaction occurred at low 122-loading (2-5 mol%) in toluene at -20 to 20 °C and furnished very good yields (88-95%) and ee values (75-99%) for the respective products (Scheme 6.120). The dependency of the catalytic efficiency and selectivity on both the presence of the (thio) urea functionality and the relative stereochemistry at the key stereogenic centers C8/C9 suggested bifunctional catalysis, that is, a quinuclidine-moiety-assisted generation of the deprotonated malonate nucleophile and its asymmetric addition to the (thio)urea-bound nitroalkene Michael acceptor [279]. 

Figure 6.61 Bifunctional hydrogen-bonding pyrrolidine-(thio)ureas utilized for Michael reactions of ketones with nitroalkenes.

Scheme 6.179 Product range of the 213-catalyzed Michael reaction of cyclohexanone with various nitroalkenes.

Nitroalkenes, e.g. 1 -nitrocyclohexene, 1-nitrocycloheptene, 1-nitrocyclooctene and (3-methyl-j8-nitrostyrene, undergo Michael addition with the enolate anions of (3-ketoesters. The resulting acids undergo a Nef reaction to give 1,4-diketones, which yield furans by subsequent ring closure (Scheme 18) (59LA(626)7l). 

Further applications of the chiral ammonium bifluoride-catalyzed enantioselective Michael addition of silyl nitronates has been shown in the reactions with nitroalkenes as a Michael acceptor (Scheme 9.17). These studies were started by examining the reaction of nitropropane-derived silyl nitronate 23b with P-nitrostyrene, using the chiral quaternary ammonium bifluoride (R,.R)-6d. When P-nitrostyrene was treated with 23b (1.2 equiv.) in the presence of (K,f )-6d (2mol%) in THF at — 78 °C, the... 

The conjugate system of the C-2 nitroalkenes should posses some interesting chemical reactivity and it should be an excellent Michael reaction acceptor with reactive nucleophiles. Moreover, the steric effect of the bulky 1,6-anhydro ring should be similar to that of levoglucosenone. As a consequence, nitroalkenes are excellent precursors for the stereoselective introduction of an additional sugar moiety at C-2 with subsequent additional functional group such as nitromethylene or its reduced/acetylated analog. Moreover, this unsaturated C-2 functionality additionally fixes the conformation of the system and most importantly sterically hinders the P-D-face of both enone molecules. 

The reactivity of the nitroalkenes has been tested in the reaction with 1-thiosugars via conventional Michael reactions catalyzed by triethylamine. In both cases the stereoselective 1,2 addition proceeds by exclusive formation of an exo-adduct via formation of an S-linkage from the less hindered face of the molecule. As expected, the shielding effect of the 1,6-anhydro bridge effectively prevents the formation of the 2-equatorial product, yielding only the 2-axial products with a new quaternary center at C-2. This provides a stable molecule, as no epimerization or p-elimination is observed during the reduction of the nitro group. 

Acceptor-substituted alkenes that are employed as substrates in Michael additions include a./l-unsaturated ketones (for example, see Figure 10.59), a,/3-unsaturated esters (Figure 10.60), and a,/3-unsaturatcd nitriles (Figure 10.61). The corresponding reaction products are bifunctional compounds with C=0 and/or C=N bonds in positions 1 and 5. Analogous reaction conditions allow Michael additions to vinyl sulfones or nitroalkenes. These reactions lead to sulfones and nitro compounds that carry a C=0 and/or a O N bond at the C4 carbon. 

---