Disubstituted Nitroolefins

Tan also examined the addition onto a,P-disubstituted nitroolefins with catalyst 52 and observed excellent diastereoselectivity (>95 5) in favor of the anti adduct. 

Scheme J4.20 Addition on

Scheme 34.21 Organocatalyzed Michael addition on activated a,P-disubstituted nitroolefins.

The group of EUman described recently the highly enantioselective and diastere-oselective addition of cydohexyl Meldrum s acid to a,P-disubstituted nitroolefins, using N-sulfinyl ureas, to give anti adducts 67 [60]. Unlike Wennemers catalyst 58, Elhnan s catalyst 68 acts through non-covalent activation. Indeed, the sulfinyl... 

Scheme 34.22 Addition of Meldrum s acid to a,P-disubstituted nitroolefins.

Vinylogous niitronate nucleophiles generated from / ,/ -disubstituted nitroolefins have been used for highly stereoselective aza-Henry reactions base catalysed by chiral... 

A means of activating a,P-disubstituted nitroolefins studied by Ma s group [59] employs an acceptor possessing an intramolecular hydrogen bond such as 61 or 62 (Scheme 34.21). The nitroolefins 63-66 without the appropriate intramolecular activation were unreactive under the same conditions. 

Interestingly, his(methylthio)-l-nitroethylene (380) reacts with dimetallic zinc-copper species leading to the corresponding exo-methylene cycloalkenes, such as 381 (Scheme 7.100) [30]. /3-Disubstituted nitroolefins are especially difficult to prepare by nitroaldol condensation. The addition of zinc-copper reagents to nitroolefins followed by a reaction with phenylselenyl bromide produces after HjOj-oxidation E/Z-mixtures of y3-disubstituted nitroalkenes, such as 382 (Scheme 7.100) [230]. 

Hoveyda and co-workers presented the asymmetric addition of alkylzincs to small-, medium-, and large-ring nitroolefins with chiral peptide-based phosphines 57 as catalyst.87 The enantioselectivities were typically >90%. Ligand 57 also worked well in the asymmetric addition of dialkylzinc to acyclic disubstituted nitroalkenes (up to 95% ee Scheme 26).88... 

Based on this gathered experience the diastereoselective alkylation of enantio-pure a-lithiated sulfonates was extended to the Michael addition with aliphatic nitroolefins [95]. Thus the Michael adducts 118 could be achieved in excellent yields (84-99%) with high diastereoselectivities de of 80-88% (84 to >98% after recrystallization or chromatography). Cleavage of the chiral auxiliary and treatment with diazomethane furnished the anti-configured a,j3-disubstituted y-nitro-methyl sulfonates 119 in overall yields of 41-70% and with excellent de- and ee-values (Scheme 1.1.32). 

Grigg has also shown that tra/M-substituted nitroolefins react with azomethine ylides in good yield (Scheme 2.35).61 Although irans-disubstituted dipolarophiles often give a mixture of endo and exo products, the diastereoselectivity was generally excellent except for ( )-2-methoxy-4-(2-nitrovinyl)phenol, which reacted with... 

The highly efficient enantioselective Friedel-Crafts reaction of pyrroles (203) with nitroolefins (204) catalyzed by the chiral phosphoric acid (154), afforded 2-substituted or 2,5-disubstituted pyrroles (205) in up to 94% ee for a wide range of substrates (Scheme 57). ... 

On the other hand, several primary amines have also been successfully employed as catalysts in the reaction using aldehydes as Michael donors. Important representative examples are shown in Figure 2.7, like bifunctional sulfamide 36 and primary amine-thioureas 37a and 23b,the latter being developed by Jacobsen and very similar to that used by the same group in the reaction with ketones as donors (see Scheme 2.7) and which performs exceptionally well in the Michael reaction of a,a-disubstituted aldehydes to both aromatic and aliphatic nitroolefins. 

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. 

The carbanion -type reactivity of dienamine activation can be promoted by a silyl-protected diarylprolinol catalyst in the presence of reactive electrophilic species, such as nitroolefins or diarylmethanols (Scheme 2.10) [20]. Although both direct addition (a-addition) and vinylogous addition (y-addition) are viable reaction pathways, the a-reactivity is the more typical one and usually provides better selectivities due to more effective shielding of the a-position by the aminocatalyst. Interestingly, the a-/y-selectivity of dienamine-mediated carbanion -type addition reactions seems to be strongly influenced by the substitution pattern of the enal reactant For example, it was demonstrated that y,y-disubstituted enals favor the a-addition product while y-functionaUzation is the predominant reaction pathway for y-monosubstituted enals. 

Seebach D, Golinski J, Synthesis of open-chain 2,3-disubstituted 4-nitroketones by diastereoselective Michael-addition of ( )-enamines to ( )-nitroolefins. A topological rule for G—G-bond forming processes between prochiral centres. Preliminary commimication. Helv. Chim. Acta 1981 64(5) 1413-1423. 

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