A,/?-unsaturated nitroalkenes

Reduction of a, -unsaturated nitroalkenes. These nitroalkenes are reduced by BHj-THF and a catalytic amount of NaBH4 to alkylanines in 85-91% yield. 

Oxa- and aza-Michael additions followed by intramolecular cyclizations occur when propargyl alcohols are treated with a, -unsaturated nitroalkenes in the presence of t-BuOK in THF. Although exo-3-methylene tetrahydrofurans are usually the major products of these reactions, 3,4-dihydropyrans are also obtained in some cases, depending upon the substituents present within the donor and acceptor. Equation 59 shows the results of the reactions of propargyl alcohol with four nitroalkenes. Similar reactions of methyl propargylamine with these same acceptors give exclusively 3-methylenepyrrolidines."... 

Formic acid is a good reducing agent in the presence of Pd on carbon as a catalyst. Aromatic nitro compounds are reduced to aniline with formic acid[100]. Selective reduction of one nitro group in 2,4-dinitrotoluene (112) with triethylammonium formate is possible[101]. o-Nitroacetophenone (113) is first reduced to o-aminoacetophenone, then to o-ethylaniline when an excess of formate is used[102]. Ammonium and potassium formate are also used for the reduction of aliphatic and aromatic nitro compounds. Pd on carbon is a good catalyst[103,104]. NaBH4 is also used for the Pd-catalyzed reduction of nitro compounds 105]. However, the ,/)-unsaturated nitroalkene 114 is partially reduced to the oxime 115 with ammonium formate[106]... 

The first example of asymmetric rhodium-catalyzed 1,4-addition of organoboron reagents to enones was described in 1998 by Hayashi and Miyaura. Significant progress has been made in the past few years. This asymmetric addition reaction can be carried out in aqueous solvent for a broad range of substrates, such as a,/ -unsaturated ketones, esters, amides, phosphonates, nitroalkenes. The enantioselectivity is always very high (in most cases over 90% ee). This asymmetric transformation provides the best method for the enantioselective introduction of aryl and alkenyl groups to the / -position of these electron-deficient olefins. 

Exposure of mixtures of alkenes, ceric ammonium nitrate, acetic acid and chloroform to ultrasound leads to a,/i-unsaturated nitroalkenes. A free-radical mechanism was proposed for this reaction (equation 126)410. 

One or both of the disadvantages are Hkely to be overcome in due course. It is obvious that a clearer picture of the mechanism of the oxidation is mandatory before much progress can be made. Once it is understood how this very simple protein folds, in the presence of organic solvent, to form a chiral cavity or chiral surface that activates the peroxide and/or enone to accomplish the desired asymmetric oxidation then the reaction may be extended to other substrates, e.g. a, unsaturated esters, nitroalkenes, perhaps (under different conditions) electron-rich alkenes. 

Scheme 6.25 Product range of the biomimetic reduction of a.P-unsaturated nitroalkenes catalyzed by 9 in the presence of 19.

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 assembly of the cyclohexene derivatives D should be feasible via an organocatalyzed domino Michael/Michael/aldol condensation sequence starting from a linear aldehyde A, a nitroalkene B and an a,(->-unsaturated aldehyde C. 

For conjugate additions to a,/ -unsaturated keto amides, see page 1599, Section 18 and page 1614, Section 20, and for nitroalkenes, see page 1511, Section 12. 

Considering that a,P-unsaturated nitroalkenes are easily available starting material, it has been reported as a unique methodology for the efficient synthesis of both 3-nitro-l,2-dihydroquinolines and 3-nitrochromenes through nitroalkenes. 

Carbamoyl nitroso dienophiles, derived from chiral pyrrolidines, have been generated and their reactivity with cyclohexa-diene investigated. Using (—)-fra/w-2,5-dimethylpyirolidine as the auxiliary, the [4 + 2] cycloadduct is isolated in 82% yield and with 98% diastereomeric excess (eq 10). Similarly, chiral ynamine dienophiles have been utilized in asymmetric [4 + 2] cycloadditions with a,p-unsaturated nitroalkenes to afford cyclic nitronic esters. The resulting esters subsequently undergo a rapid [1,31-rearrangement to afford chiral cyclic nitrones in moderate yield and high diastereoselectivity (eq 11)-... 

The stereodiemical trends discussed above are not limited to a -unsaturated carbonyl compounds other Midiad acceptors sudi as nitroalkenes and unsaturated phosphane oxides display similar behavior. A representative example for the nitroalhene dass of Midiael acceptors is shown with substrate 70 in Scheme 6.13 [28]. The best results were thus obtained for arylcuprates. Other oi anocuprates were much less selective which severely restricts their application in organic synthesis. 

For the transfer of arj l and alkenyl groups to enones, Hayashi s procedure, employing the corresponding boronic adds and a rhodium-BINAP catalyst, is the method of choice at present [24, 25]. For the transfer of alkyl groups to cydic enones the use of dialkylzinc reagents in the presence of copper-phosphoramidite catalysts is superior. Although the first examples of hi ly enantiosdective 1,4-ad-ditions of R Zn reagents to nitroalkenes have been reported, similar catalytic methods for numerous other dasses of a, -unsaturated compounds still need to be devdoped. 

The reduction of a,p unsaturated nitroalkenes provides a simple access to a vast array of functionalities, including amines. Early studies focused on the catalytic hydrogenation of the nitropropene derivative (52) 1 -(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (53) is obtained as a minor product in a... 

Urea-hydrogen peroxide (UHP) has been found to epoxidize electron-deficient alkenes under various conditions <90SL533,93MI 103-03) for example, methyl methacrylate is epoxidized with UHP-Na2HP04 in the presence of (CF3C0)20 a,//-unsaturated ketones and nitroalkenes are cleanly transformed into the corresponding oxiranes with UHP-NaOH in methanol (Equation (37)). 

Reductions. Disulfides are cleaved, and nitroaryl azides are reduced to the amines without affecting the nitro group or other substituents. However, p.y-unsaturated nitroalkenes are reduced to enones, and m-nitrostyrenes give a-allyloxy arylacetaldoximes in the presence of allyl alcohol. ... 

Modification of the strategy provides several routes to oxime ethers.465 Various a,8-unsaturated nitroalkenes were readily reduced to the corresponding oximes by sodium hypophosphite in the... 

The cycloaddition, reduction, and oxidation reactions of a,/i-unsaturated nitroalkenes provide easy access to a vast array of functionality that includes nitroalkanes, N-substituted hydroxylamines, amines, ketones, oximes, and a-substituted oximes and ketones [82-84]. Consequently, there are numerous possibilities of using these in situ generated nitroalkenes for preparation of valuable building blocks and synthetic precursors. 

An alternative synthetic route to (bicyclic) pyrroles 41 involves the coupling of a cyclic ketone with an amine and an a,/i-unsaturated nitroalkene on the surface of alumina (Scheme 17.30) [14]. After MW irradiation for 13-15 min the product 41 was obtained in 71-86% yield. In this synthesis, substitution on the a-position of... 

Bp3-OEt2 followed hy DiisobutyUduminum Hydride is used for the 1,2-reduction of y-aimno-Q, -unsaturated esters to give unsaturated amino alcohols, which are chiral building blocks for a -amino acids. Q , -Unsaturated nitroalkenes can be reduced to hydroxylamines by Sodium Borohydride and BF3-OEt2 in THF extended reaction times result in the reduction of the hydroxylamines to alkylamines. Diphenylamine-borane is prepared from sodium borohydride, BF3-OEt2, and diphenylamine in THF at 0 °C. This solid is more stable in air than BF3-THF and is almost as reactive in the reduction of aldehydes, ketones, carboxyhc acids, esters, and anhydrides, as well as in the hydrob-oration of alkenes. 

DMAP Catalysis to Form Key Substructures. DMAP has been used as a catalyst in the Morita-Baylis-HiUinan (MBH) reaction. Conjugated nitroalkenes can be reacted with an amine base to form a zwitterionic species that can add to many types of ketones and aldehydes. Remarkably, only DMAP and imidazole were able to effectively catalyze this reaction, likely due to their small size and ability to stabilize the intermediate. In another example, a unique catalyst system involving 1 1 1 DMAP TMEDA Mgl2 (each in 10 mol %) allowed the MBH reaction to proceed in fairly high yields between aldehydes and a , -unsaturated ketones, esters, or a thioester. ... 

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