Nitroalkenes hydrogen-bonding

A systematic study on enzymatic catalysis has revealed that isolated enzymes, from baker s yeast or old yellow enzyme (OYE) termed nitroalkene reductase, can efficiently catalyze the NADPH-linked reduction of nitroalkenes. Eor the OYE-catalyzed reduction of nitrocyclohexene, a catalytic mechanism was proposed in which the nitrocyclohexene is activated by nitro-oxygen hydrogen bonds to the enzymes His-191 and Asn-194 [167, 168]. Inspired by this study Schreiner et al. 

Scheme 6.104 Key intermediates of the proposed catalytic cycle for the 100-catalyzed Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes Formation of imine (A) and F-enamine (B), double hydrogen-bonding activation of the nitroalkene and nucleophilic enamine attack (C), zwitterionic structure (D), product-forming proton transfer, and hydrolysis.

Chen and co-workers presented, in 2007, a Michael-type Friedel-Crafts reaction of 2-naphthols and trans-P-nitroalkenes utilizing the bifunctional activating mode of cinchonine-derived catalyst 117 [277]. The nitroalkene was activated and steri-cally orientated by double hydrogen bonding, while the tertiary amino group interacts with the naphthol hydroxy group to activate the naphthol for the nucleophilic P-attack at the Michael acceptor nitroalkene (Scheme 6.117). 

Figure 6.61 Bifunctional hydrogen-bonding pyrrolidine-(thio)ureas utilized for Michael reactions of ketones with nitroalkenes.

A pyrrolidine-thiourea organocatalyst (69) facilitates Michael addition of cyclohexanone to both aryl and alkyl nitroalkenes with up to 98% de and ee 202 The bifunctional catalyst (69) can doubly hydrogen bond to the nitro group, leaving the chiral heterocycles positioned for cyclohexyl enamine formation over one face of the alkene. 

Nitroalkenes react enantioselectively (ee usually 40%) with indoles using chiral hydrogen-bonding bis-sulfonamides as catalysts [e.g. to form (41)].44 An enantioselective reaction (usually ee 83-95%) has been shown to occur between indoles and ethyl ... 

When, on the other hand, organocatalyst 133 (possessing a bulky 2,5-diaryl-pyrrole moiety) is applied, product 134 was selectively formed by a highly diastereo- and enantioselective 1,3-dipolar cycloaddition (11 examples, 56-90%, 60-91% ee). This reaction most likely involves activation of the nitroalkene by the thiourea, via the earlier mentioned doubly hydrogen-bonded interaction, followed by a concerted attack of the in situ formed azomethine ylide (this ylide is not activated by nor coordinated to the organocatalyst, because of the bulky, nonbasic pyrrole group, but is most likely formed via a 1,2-prototropic rearrangement [92]). 

The proposed reaction mechanism is shown in Scheme 6.75. The nitroalkene moiety of bifunctional ortAo-alkyne-substituted nitrostyrenes 159 is activated through hydrogen bonding with catalyst 160 to incorporate the stereoehemieal information in the first AFC reaction. Then the alkyne is activated under gold catalysis to affect the seeond AFC/ring expansion cascade. 

In 2010, Bernal, Fernandez, and Lassaletta [198] disclosed an unprecedented asymmetric cyanosilylation of nitroalkenes that was catalyzed enantioselectively by a quinine derivative with tetraalkylammonium cyanide and thiourea moieties. The activation of the nitroalkene takes place by hydrogen bonding to the thiourea, while the tetraalkylammonium cation moiety binds the cyanide anion, which is dehvered stereoselectively to the double bond. 

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