Nitroalkenes Lewis acid-activation

Finally, the Lewis acid activation of a,)6-unsaturated carbonyl compounds and Q -nitroalkenes is sufficient to induce productive Sr reactions with allenylstannanes (Scheme 5.2.70). Haruta and Kita have successfully achieved condensation reactions with 326 and 328 in the presence of TiCU, and cyclo-hexenones 330 and 332 also serve as synthetically effective substrates for the 1,4-conjugate addition. In the case of enone 332, activation with TBSOTf led to the isolation of silyl enol ether 333. ... 

Intramolecular [4+2] cycloadditions of nitroalkenes Reactivity and selectivity in [4+2] cycloadditions of nitroalkenes without Lewis acid activation Nitronates as dipoles in [3+2] cycloadditions Chemistry of nitroso acetals Definition of different variants of the tandem [4+2]/[3+2] cycloadditions of nitroalkenes... 

Cycloaddition reactions represent another important area of nitro olefin chemistry. Typically, nitroalkenes react in normal-electron-demand [4 + 2] cycloadditions as highly activated dienophiles (2ji-components) and produce nitro-substimted cyclohexenes [53]. However, under certain conditions nitroalkenes can switch the mode of reactivity in cycloadditions (periselectivity) and behave as electron-poor heterodienes (47i-components). Nitroalkenes react as 471-partners with electron-rich dienophiles under Lewis-acid activation [19], high pressure [54], and even thermal activation in some cases [55-57]. The products of such cycloadditions are six-membered cyclic nitronates (see Scheme 16.2, for example), whose properties will be discussed later in this text. 

Reactivity and Selectivity in [4+2] Cycloadditions of Nitroalkenes Without Lewis Acid Activation... 

The Lewis-acid promoted [4 + 2] cycloadditions are the most extensively smdied. However, nitroalkenes can react as heterodienes without Lewis acid activation under high pressure as well [100]. For example, the cycloaddition of nitro-alkene 44 (Scheme 16.18) with ethyl vinyl ether is accelerated in a pressure-dependent manner but does not stop after the [4 + 2] step [101]. The intermediate nitronate 67a undergoes a further [3 + 2] cycloaddition to form nitroso acetal 68a as the major product (67a/68a l/6). Complete conversion is observed at pressures above 8 kbar after only 1 h. For comparison, the same reaction requires a large excess (90 equiv) of the dienophile to reach completion at ambient pressure in ethanol after 5 days. Nitronate 67a is formed with... 

A few examples of cycloadditions between nitroalkenes and vinyl ethers without the use of Lewis acids have been reported (Eq. 8.105), in which additional activating electron-withdrawing groups are generally required.161... 

The third cycloaddition substrate explored the feasibility of a vinyl nitro functionality as an activated dipolarophile (98, Scheme 1.9c). Preparation of nitroalkene oxidopyridinium betaine 98 began with silylenol ether 92, which was treated with methoxydioxolane in the presence of Lewis acid catalyst, TrC104, to afford keto dioxolane 93 in 58 % yield [47]. Ketone 93 then underwent a-nitration by treatment with /-BuONCL and KOt-Bu to provide nitro ketone 84 (91 %), which was then converted to the nitroalkene functionality via reduction under Luche conditions to... 

Synthesis of Substituted Pyrrolidines. A cycloaddition/red-uction sequence between nitroalkenes and vinyl ethers derived from DCP, i.e., 2 can effect the enantioselective synthesis of substituted pyrrolidines. 2-Substituted 1-nitroalkenes undergo highly efficient and diastereoselective Lewis-acid-promoted [4 + 2] cycloaddition with DCP-derived vinyl ethers to afford cyclic ni-tronates 5 in high yields. Subsequent reduction with Pt02 (7.5 mol%), under 160 psi of H2 at room temperature for 24 h, affords the optically active 3-substituted pyrrolidines (6) (71-97%, both as the free base and V-protected derivatives), and the chiral auxiliary 1 (eq 3). 

Nitroalkene could also be activated by Lewis acids, e.g., Sc(OTf)3, Yb(OTf)3, and Zn(OTQ2 to increase its electrophilicity. According to the unpublished result in Pfaltz group, the cascade process could be facilitated by Yb(OTf)3, which furnished the cyclized product 91 in 60 % yield at 80 °C within 12 h (Scheme 36). The transformation was diastereospecific and only anti diastereomer was observed. The diastereoselectivity can be explained through Zimmer-Traxler transition state H in which the orientation of substituents would be pseudoequatorial, leading to the anti-product via intramolecular nucleophilic attack. 

Among the few examples of pure acidic activation in Michael addition to nitroalkenes, the recent works of Ooi and coworkers described the aza-Michael addition of aniline [50] by the charged chiral C2 symmetric phosphonium 50 (Scheme 34.16). Indeed, the acidic spirocycUc catalyst 50 was able to asymmetrically activate a Lewis base such as 2,4-dimethoxyaniline, to promote the addition to nitroolefins with excellent yields and selectivity. 

Several other double intermolecular [4 + 2]/[3 + 2] cycloadditions of nitroalkenes have been reported [74], many of which do not involve Lewis acid promoters but rather employ thermal [55, 56, 66e, 97,118, 152] or high pressure [54,101, 102, 153] activation. 

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