E-nitroolefins

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

Evolving the Pentaerythritol Tetranitrate (PETN) Reductase as a Catalyst in the Reduction of a,p-Unsatuiated Carbonyl Compounds and E>Nitroolefins... 

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. 

A similar asymmetric nitroolefination reaction has been described that uses an optically active / -nitro-a,/ -unsaturated sulfoxide, e.g., 2-nitro-1-[(/ )-2-phenylpropylsulfmyl]cyclohexene, where the chiral sulfoxide moiety functions as a leaving group. Condensation oflactam enolates with this sulfoxide affords substituted lactams with high enantiomeric excesses and good yields27. 

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). 

Whereas the examples discussed so far proceed according to the iminium ion mechanism (A), amine-catalyzed additions of, e.g., ketones to nitroolefins are effected by intermediate enamine formation (B). List et al. were the first to report that L-proline catalyzes the addition of several ketones to nitroolefins (Scheme 4.23). Whereas both the yields and diastereoselectivity were high in DMSO as solvent, the ee did not exceed 23% [38]. A related study of this process by Enders and Seki resulted in identification of methanol as a superior solvent, and enantioselec-tivity up to 76% was achieved (Scheme 4.23) [39]. 

In the presence of 10 mol% of this catalyst, the malonates 56 could be added to several nitroolefins 57 with up to 93% ee. Apolar solvents such as toluene are crucial for high ee values. It is also noteworthy that (i) good ee can be achieved with catalyst 55 even in the absence of solvents, i.e. with a mixture of the neat starting materials 56 and 57, and that (ii) the range of Michael donors/acceptors includes aryl- and alkyl-substituted nitroolefins and 2-alkylated malonates. 

Serrano, J A, Moreno, M C, Rom, E, Arjona, O, Plumet, J, Jimenez, J, Enantioselective s3mthesis of cyclohexene nitro aldehydes via Diels-Alder reactions with sugar nitroolefins, J. Chem. Soc. Perkin. Trans 1, 3207-3212, 1991. 

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]. 

Enamines (e.g. 377) have been shown to react with conjugated nitroolefins 378 to give mainly dihydro-l,2-oxazine A -oxide derivatives 379 as products of kinetic control (sometimes a cyclobutane ring is formed in these reactions see Section II.B). The stability of these heterocycles is largely dependent on the parent enamine and the type of substituent used on the nitro olefin as has been extensively studied by Valentin and coworkers " . Usually they open into the corresponding nitroalkylated enamines 380 (equation 82), in particular in a solution of methanol or deuteriated chloro-and often an equilibrium between the two forms is established. Stable 1,2-oxazine A -oxides have been obtained in the reaction of 2-nitro-l,3-dienes with cyclic enamines . 

Nucleophilic phosphanes can also be used for olefin isomerization. Nitroolefins having a substituent on the nitro group, readily available via the nitro aldol reaction followed by dehydration, often give a mixture of (E)- and (Zj-isomers. By adding catalytic amounts of polymer-supported triphenylphosphane, the (Z) -isomer could be isomerized to the corresponding (Ej-isomer, in most cases with total (E)-selectivity [30]. 

Xu, et al. developed an asymmetric organocatalytic Diels-Alder reaction of cyclohexenones (e.g., 38) with aromatic nitroolefins 60 in seawater and brine with excellent chemo-, regio- and stereoselectivities, Scheme 3.24 [38]. The study suggested that seawater or brine play a role in stabilizing the transition state through a hydrogen-bonding interaction and the cycUzation is involved in the one-step concerted addition pathway rather than a sequence of the Michael-Michael mechanism. 

A facile access to A-sulfonylimidates and their synthetic utility for the transformation to amidines and amides, (b) E. J. Yoo, S. H. Park, S. H. Lee, S. Chang, Org. Lett. 2009, 11, 1155-1158. A new entry of copper-catalyzed four-component reaction facile access to a-aryl P-hydroxy imidates. (c) R. Husmann, Y. S. Na, C. Bohn, S. Chang, Chem. Commun. 2010, 46, 5494—5496. Copper-catalyzed one-pot synthesis of a-functionalized imidates. (d) W. Song, W. Lu, J. Wang, P. Lu, Y. Wang, J. Org. Chem. 2010, 75, 3481-3483. A facile route to y-nitro imidates via four-component reaction of alkynes with sulfonyl azides, alcohols, and nitroolefins. (e) G. Murugavel, T. Punniyamurthy, Org. Lett. 2013, 15, 3828—3831. Novel copper-catalyzed multicomponent cascade synthesis of iminocoumarin aryl methyl ethers. 

In contrast to the reduction of carbonyl-activated substrates (e.g., cydohexenone), which is known to be concerted, it has been demonstrated that in the reduction of nitrocyclohexene and other simple nitroolefins the hydride transfer and the proton transfer are separate steps, forming the nitronate ion as a freely dissociable intermediate [95,96]. 

PETN reductase appears to be an industrially viable enzyme due to its robustness [10,44]. It catalyzes the reduction not only of aromatic nitro compounds, but also of activated alkenes such as unsaturated aldehydes and ketones [10,44]. Of particular synthetic interest is its ability to catalyze the reduction of prochiral E- and Z-a,(3-unsaturated nitroolefins leading to chiral nitro products. The mechanism is shown in Figure 5.7. 

Table 5.4 Catalytic performance ofWT PETN reductase and mutants in the stereoselective reduction of E-configurated nitroolefins using an NADPH regeneration system [32,39],...

Based on the characteristic features of this neutral phase-transfer reaction, an assumed catalytic cycle of the conjugate addition of 3-aryloxindole was proposed as shown in Scheme 14.6. For the promotion of the reaction, the combination of the H20/toluene biphasic reaction system with a lipophilic phase-transfer catalyst such as (S)-7 was indispensable. In the formation of ammonium enolate 8, HBr is simultaneously generated, and in the case of toluene solvent alone the reaction mixture becomes homogeneous and hence the reverse reaction from 8 to 7 (i.e., protonation of 8) may be fast. However, in the H20/toluene biphasic reaction system, hydrophiUc HBr moves into the water phase smoothly, while UpophiUc ammonium enolate 8 remains in the toluene phase. Consequently, protonation by the contact of ammonium enolate 8 and HBr was suppressed, and hence the transformation from 7 to 8 was efficiently promoted. Then, ammonium enolate 8 and nitroolefin would combine in the toluene phase to promote the conjugate addition step (8 to 9 in Scheme 14.6) smoothly. 

Geertsema, E. M., Miao, Y, Tepper, P. G., de Haan, R, Zandvoort, E., and Poelarends, G. J., Biocatalytic michael-type additions of acetaldehyde to nitroolefins with the proline-based enzyme 4-oxalocrotonate tautomerase yielding enantioenriched y-nitroaldehydes. Chem. Eur. J. 2013,19 (43), 14407-14410. 

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