Nitroolefins cycloadditions

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

Diels-Alder cycloadditions of enaminothiones with electrophilic die-nophiles (83AHC145, section III,G) have been widely used for the preparation of various thiopyran derivatives. In addition to expected 2H-thiopyrans, 4//-isomers were trapped as intermediates or even as final products. Nitroolefines (90T1951), olefinic carbonyl derivatives [80JH405 85JOC1545 92JCS(P1)2603] allenedicarboxylic esters... 

The total syntheses of the potent glycosidase inhibitors (+)-castanospermine, (+)-6-epicas-tanosperimine, (+)-australine, and (+)-3-epiaustraline have been reported. These four natural products are derived from a single common intermediate, the nitroso acetal (as shown in Scheme 8.43), which is created in the key step by the asymmetric tandem [4+2]/[3+2] cycloaddition between silaketal nitroolefin and chiral vinyl ether.182 The strategy of the synthesis is outlined in Scheme 8.43. Scheme 8.44 presents a total synthesis of (+)-castanosperimine and (+)-6-epi-castanosperimine from the common intermediate prepared by tandem [4+2]/[3+2] cycloaddition. 

As follows from above, the rate of [4+ 2]-cycloaddition of nitroolefin (42) is determined by the nature of partner (43) and decreases in the following series of olefines electron-rich > electroneutral > electron-deficient (100). 

Some additional examples, where the stereochemical outcome of the cycloaddition to chiral alkenes has been explained in terms of the Honk—Jager model, should also be mentioned. The diastereomer ratio found in the reaction of y-oxy-a,p-unsamrated sulfones (166), with Morita-Baylis-Hillman adducts [i.e., ot-(a -hydro-xyalkyl)-acrylates (167)] (Scheme 6.27), with dispiroketal-protected 3-butene-l,2-diol (168), and with a,p-unsamrated carbonyl sugar and sugar nitroolefin (169) derivatives, all agree well with this model. 

Cycloaddition of above-mentioned sugar nitrones 42, 43, and 61 with ni-troalkenes 77, including sugar nitroolefins, led with complete regioselectivity to 4,5-trfl 5-4-nitroisoxazoHdines 78-80 in 51-78% global yields (Fig. 17). The endolexo stereoselectivity depends on the type of sugar derivative... 

High enantioselectivites in the aza-Michael reaction have been achieved using alternate organocatalysts, and the addition of benzotriazole to nitroolefins occurs with up to 94% ee using bifimctional catalysts such as (11.64). Guerin and Miller have developed an alternate approach to the enantioselective introduction of triazoles based on the asymmetric conjugate addition of azide followed by a 1,3-dipolar cycloaddition of the product with an alkyne. In this approach, the addition of hydrazoic acid to Michael acceptors such as (11.133) proceeds with good ee in the presence of the dipeptide (11.134). ... 

TBAF efficiently unmasks nucleophilic azide for C-N bond formation. TBAF stimulated the reaction of benzonitrile with TMSN3 to form 5-substituted IH-tetrazoles (eq 45). Under similar conditions, 4-aryl-lH-l,2,3-triazoles can be synthesized by TBAF-catalyzed cycloadditions of electron poor nitroolefins (eq46). 2 - 25... 

Hoveyda and co-workers employed nitroolefinic silanes 249 possessing a chiral center that bears a silicon substituent for the diastereoselective synthesis of isoxazolines 251 (Scheme 59) [160]. While the silyl nitronate cycloaddition provided the diastereomeric isoxazolines 251 in >20 1 ratio, the nitrile oxide route was much less selective (dr 1 2), in agreement with the findings by Hassner as shown in Scheme 49. The greater selectivity observed in the ISOC reaction was attributed to a possible 1,3-aUylic strain in the transition state leading to the minor isomer while no such strain was expected for nitrile oxides that have near-linear geometry. The authors also observed greater... 

An organocatalytic asymmetric formal [3 + 2] cycloaddition reaction of isocya-noesters 218 to nitroolefins 210 leading to highly optically active dihydropyrroles 220 was reported by Gong, et al., Scheme 3.70 [87], The proposed mechanism is depicted in Scheme 3.70 the cinchona alkaloid chiral base 219 promote an asymmetric Michael addition of isocyanoesters to electron-deficient olefins (nitroolefins), and subsequent intramolecular cyclization of the intermediate to afford the dihydropyrroles 220. 

Scheme 3.70 Organocatalytic [3+2] cycloadditions of a-substituted isocyanoesters with nitroolefins...

Later, J0rgensen and co-workers [71] and Vicario and co-workers [72] simultaneously reported a cooperative dienamine/hydrogen-bonding catalytic system for the enantioselective formal [2+2] cycloaddition of enals to nitroolefins catalyzed by the bifimctionalized cyclobutene catalyst 116 (Scheme 6.27). 

In a few specialised examples 1,3-dien-2-amines were found to undergo a [4+2] cycloaddition with nitroolefins to form tricyclic derivatives of 4-nitrocyclohexenylamine. 

Dihydroisoquinoline esters undergo an oxidative [3 + 2] cycloaddition with nitroolefines or N-sulfuryl aldimines when treated with a cobalt catalyst (Scheme 69) (130BC6691). This cycloaddition provides a fairly robust approach to dihydropyrrolo[l,2-rj]isoquinolines. Nitroolefins with a number of aryl substituents underwent reaction with the dihydroiso-quinolines.The aryl groups could have either electron-donating (methoxy)... 

These authors also reported the first catalytic asymmetric 1,3-dipolar cycloaddition between a-substituted isocyanoesters and nitroolefins by using a cinchona alkaloid derivative as the organocatalyst to afford chiral 2,3-dihy-dropyrroles with high diastereo- and enantioselectivities of up to > 90% de and >99% ee, respectively. The best results are collected in Scheme 6.17. 

The FeCl3-catalysed 3 -I- 2-cycloaddition of nitroolefins and IV-aryl benzamidines produced multi-substituted imidazoles in good yields. ... 

Scheme 7.26 Synthesis of 4-aryl-NH-1,2,3-triazoles via p-toluenesulfonic acid mediated 1,3-dipolar cycloaddition of nitroolefins with NaNa...

Scheme 8.48 Cul-catalyzed synthesis of polysubstituted imidazole derivatives via intermolecular [3+2] cycloaddition reaction of nitroolefins and amidines.

The synthetic utility of the bifunctional catalysts in various organic transformations with chiral cyclohexane-diamine derived thioureas was estabhshed through the works of Jacobsen, Takemoto, Johnston, Li, Wang, and Tsogoeva. In the last decade, asymmetric conjugate-type reactions have become popular with cinchona alkaloid derived thioureas. The next section presents non-traditional asymmetric reactions of nitroolefins, enones, imines, and cycloadditions to highhght the role of chiral Br0nsted base derived thiourea catalysts. 

On the other hand, modified-imidazoHdinones endowed with imidazole (125) [149] or a fluorous tag in the side chain (126) [150] proved to be active in the Diels-Alder cycloaddition in the presence of 5 vol.% water (Figure 24.40). The highly efficient organocatalyst 127 promoted, in the presence ofp-(trifluoromethyl) benzoic acid, the asymmetric Diels-Alder reaction of cyclohexenones with aromatic nitroolefins in seawater and brine with excellent chemo-, regjo-, and stereoselectivities [151], It has been postulated that the cychzation was involved in a concerted addition process and that seawater and brine significantly promoted the... 

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