P, -Disubstituted nitroalkenes

Scheme 4.58 Enantioselective conjugate reduction of p,P-disubstituted nitroalkenes.

Recently, the Jia group reported AFC alkylation reactions of p,p-disub-stituted nitroalkenes with indoles. The AFC alkylation of indoles with p-CFa-p-disubstituted nitroalkenes 148 and acyclic a-substituted-p-nitroacry-lates 149 was achieved by using Ni(Cl04)2/bisoxazoline 147 complex as a catalyst, affording indoles bearing an all-carbon quaternary stereogenic center in good yields with excellent enantioselectivity (up to 97% ee) (Scheme 6.67). ... 

Scheme 6.67 Ni(Cl04)2/bisoxazoline 147 complex catalyzed AFC alkylation of indoles with P-CFj-p-disubstituted nitroalkenes 148 and acyclic a-substituted-P-nitroacrylates 149 reported by Jia.

Figure 6.7 A proposed model for asymmetric induction of the Ni-catalyzed AFC alkylation reactions of p,p-disubstituted nitroalkenes with indoles.

Alternative to the Nef pathway, some OYEs can bioreduce p,p-disubstituted nitroalkenes to oxazetes. This reaction proceeds through reduction of the nitro group to the nitroso alkene, which spontaneously forms 1,2-oxazete derivatives. At elevated temperatures by a retro-[2 + 2]-cycloaddition, HCN and the ketone are formed as final products. The bioreduction pathway was determined by the OYE used. Thus, using xenobiotic reductase A oxazete formation was predominant, while the PETN reductase-catalyzed process favored the Nef pathway (Scheme 2.15). 

As an alternative approach to classical OYE-like ene reductases, also cell-free extracts of anaerobic bacteria such as Clostridium sporogenes were tested for the bioreduction of a library of nitroalkenes [106]. The iron-sulfur cluster dependent enoate reductases responsible for the C=C bioreduction in Clostridia showed the same stereopreference of OYEl-3 on ( )-81 and related nitroolefins. As with ene reductases, nonaromatic substrates were converted more slowly and a,P-disubstituted nitroalkenes yielded almost racemic products. The relatively low deuterium exchange rate at the a-position (employing a biphasic system) confirmed also in this case that the low optical purity of the products is mostly due to the bioreduction itself, rather than to chemical racemization. 

Scheme 59 Coppcr-peptide-catalysed ECA of organozinc reagents to p.p-disubstituted (Z)-nitroalkenes by Zeng [91]...

Fryszkowska, A., Fisher, K Gardiner, (. M and Stephens, G.M. (2008) Highly enantioselective reduction of p,p-disubstituted aromatic nitroalkenes catalyzed by Clostridium sporogenes. /. Org. Chem., 73,4295 298. 

Selectivity in the Fused-Mode Intramolecular [3+2] Cycloadditions of Nitronates The most intensively investigated family of the intramolecular cycloadditions is the fused mode (Scheme 16.32) [76]. In this mode regio-, stereo-, and facial selectivity are completely governed by the tether, which is attached at C(4) of the nitronate. Such nitronates are prepared by [4 + 2] cycloadditions of nitroalkenes that bear the dipolarophile tethered at C(2). These nitroalkenes are typically prepared by a two-step procedure involving Henry reaction followed by dehydration [128]. Selenoxide elimination has been employed in the preparation of a P, 3-disubstituted nitroalkene [90]. Nitronates tethered at C (4) with two-carbon and three-carbon chains coimecting the... 

Lu H, Zhang F, Meng X, Duan S, Xiao W. Enantioselective Michael reactions of p,(3-disubstituted nitroalkenes a new approach to (3 -amino acids with hetero-quaternary stereocenters. Org. Lett. 2009 11 3946-3949. 

Remarkably, the reaction also tolerated the use of differently substituted a-alkyl-p-ketoesters as Michael donors, leading to the formation of compounds containing two contiguous stereogenic centers, one of them a quaternary one, in good diastereo- and enantioselectivities (Scheme 4.6). Masked cyclic 1,3-diketones such as 2-hydroxy-1,4-naphthoquinols have also been successfully applied in this context also showing the extraordinary performance of catalyst 68a in terms of both yields and enantioselectivities. There is also one example of a vinylogous Michael reaction between a,a-disubstituted dicyanoacrylates and nitroalkenes for which Takemoto s catalyst has also been identified as the most efficient promoter of the reaction. Moreover a solid-supported version of this catalyst has also been developed by Takemoto himself and tested in the reaction of diethylmalonate with nitrostyrene with success. ... 

Based on their previous achievements in die Michael reaction of unmodified aldehyde [51], Chen and co-workers [16] recently developed the pyrrolidinyl-camphor derivatives as a new class of organocatalysts for the Michael addition of a,a-disubstituted aldehydes to nitroalkenes. In the presence of 22, the reactions were proceeded in high to excellent yields and enantioselectivities for symmetric a,a-disubstituted aldehydes and a wide range of p-nitroalkenes. However, poor enan-tiocontrol was obtained for unsymmetric a,a-disubstituted aldehydes (Scheme 5.8). 

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