Electrophiles nitroolefines

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... 

According to Urbanski (Ref 6), . . Besides adding concentrated HN03 to olefms, true nitration of olefins thru electrophilic substitution can take place to yield nitroolefins.. . In 1878 Haitinger (Ref 1) found that nitration of isobutylene with anhydrous nitric add led to several products, among which was nitroisobutylene (CH3)C2=CHN02, in 10% yield... 

Since the trapping of the lactam enolate with electrophiles should not be limited to nitroolefins, extension to conjugate additions to alkenylsulfones, the ring opening of N-tosylaziridines, alkylation with functionalized halides, and silylation with chlorotrimethylsilane were explored. 

An example for the use of the boron-zinc exchange reaction for copper-mediated SN2 -substitutions of allylic electrophiles is the hydroboration of nitroolefin 130 with diethylborane, followed by successive transmetallation of the borane 131 with diethylzinc and CuCN-2LiCl, and final trapping with allyl bromide to give the product 133 with 83% yield over four steps (Scheme 34).34,34a This transformation again demonstrates the tolerance of the method towards functional groups and acidic hydrogen atoms. 

The electrophilic character of aliphatic nitroolefins and the synthetic equivalency of nitro and carbonyl groups have been exploited in a recently developed regiospecific route to bicyclo[3.3.0]octenones (Scheme 12).63 With stannic chloride as catalyst,... 

The overall reaction makes it possible to perform intramolecular caibozincations [65-71] via a radical cyclization. This useful preparation of cyclopentylmethylzinc derivatives proceeds with excellent stereoselectivity and allows preparation of quaternary centers. After cyclization, the zinc organometallic can be transmetallated with CuCN-2LiCl and made to react with a broad range of electrophiles such as acid chlorides, allylic and alkynyl halides, ethyl propiolate, 3-iodo-2-cyclohexen-l-one, and nitroolefins such as nitrostyrene, leading to products of type 40 (see Section 9.6.9 Scheme 9-34) [65,70]. 

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]. 

Use ofenamine or iminium electrophiles. In their synthesis of spirotryprostatin B (133), Fuji and co-workers started from rac-3-prenyl-2-oxindole (149) with an interesting enantioconvergent nitroolefination affording the C3-quatemised product 151 ee 78%, Scheme 30). The proline-derived nitroenamine 150 was used with the pyrrolidine section functioning as auxiliary [135, 136]. 

On the other hand, chiral primary amine-thiourea catalysts 85 and 90 developed by Tsogoeva [125] and Jacobsen [130], respectively, show an opposite sense of relative stereoinduction in the conjugate addition of acyclic ketones to nitroolefins (see Scheme 2.41 for 90). These anti selective catalysts stand in contrast to the usually obtained results which lead to selective formation of the i yn-conflgured diastereoiso-mers. The unexpected situation suggests participation of a Z-enamine intermediate. Moreover, with respect to the electrophile activation by the urea-type catalysts, it is also demonstrated that only one oxygen of the nitro group is bound to the thiourea moiety in an out-of-plane arrangement [125,130]. 

A similar scenario has been demonstrated by Najera et al. to support the bifunc-tional Br0nsted acid-base organocatalytic character and the origin of the observed enantioselectivity achieved by protonated 2-aminobenzimidazol-derived catalyst 163 in the conjugate addition of malonates and 1,3-diketones to nitroolefins [251]. DFT calculations have shown that the lowest energy transition state corresponds to the addition of the malonate or diketone to the electrophile with activation of the nucleophile by formation of two hydrogen bonds with the amino-benzimidazole moiety and activation of the nitroolefin better achieved by the protonated tertiary amine (C, Fig. 2.19). 

With respect to nitroolefins as electrophiles, indoles [335-337], 4,7-dihydroindoles [338], pyrroles [339], and naphthols [340] have been nsed with success in the reaction employing different chiral bifunctional organocatalysts. Scheme 2.118 shows... 

Regarding the hydroxylation of nitroolefins, the reaction is performed under hydrogen-bonding catalysis using quinine-derived thiourea 170 (5 mol%), ethyl glyoxylate oxime as nucleophile in toluene at -24°C [374], This process, which constitutes a valid alternative to the Henry reaction, yields the corresponding hydroxylated nitrocompounds in good yields (63-83%) and enantioselectivities (48-93% ee) from ahphatic electrophiles (styrene derivatives are prone to retio-Michael addition) and has been successfully employed in the synthesis of optically active P-amino alcohols (Scheme 2.132) [375]. 

A quaternary stereogenic carbon center was effectively cOTistructed by the y-selective conjugate addition of this class of nucleophile to highly electrophilic, P-trifluoromethyl nitroolefins using cinchona alkaloid-derived thiourea 19c as a... 

Highly diastereo- and enantio-selective catalytic capture of chiral zinc enolates using nitroolefins as electrophiles has been described. The tandem y-nitro ketone products were obtained in the presence of a monodentate phosphoramidite ligand, in good yields with high diastereo- and enantio-selectivities (up to 96% ee). 

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