Steric Henry reaction

Thus, various kmds of bases are effective in inducing the Henry reaction The choice of base and solvent is not crucial to carry out the Henry reaction of simple nitroalkanes v/ith aldehydes, as summarized in Table 3 1 In general, sterically hindered carbonyl or nitro compounds are less reactive not to give the desired ni tro-aldol products in good yield In such cases, self-condensation of the carbonyl compound is a serious side-reaction Several mochfied procedures for the Henry reaction have been developed... 

The chemical yield of the classical Henry reaction is not always good and depends on steric factors thus, highest yields are obtained when nitromethane is used. Performing the reaction under high pressure (9 kbar, 30 °C) with tetrabutylammonium fluoride catalysis19 enlarges the scope of the reaction dramatically. Thus, addition of nitropropane to 2-methylcyclohexanone, which is not reactive under the classical conditions, was achieved in 40 % yield. Improved yields... 

In fact, cyclization (16 5b) is an intramolecular modification of the classical Henry reaction. It should be noted that the Henry reaction generally occurs as C,C-coupling (path (b)), but the reaction can be forced to proceed by path (a) due to steric hindrance or other factors. 

Strongly chelating ligands provide a sterically rigid ligand frame, a prerequisite for induction of asymmetry at the lanthanide center. Complexes derived from (S)-( — )-BINOL were thoroughly studied in the nitroaldol reaction (Henry reaction, Scheme 27) [250]. 

Quite recently, Bandini, Umani-Ronchi and coworkers also reported the highly enantioselective Henry reaction of the various trifluoromethyl ketones 54 with nitromethane catalyzed by the C6 -hydroxy quinine derivatives S3 (5 mol%) [24]. Various aliphatic and aromatic ketones were smoothly converted to the desired tertiary carbinols SS in high yields and ee values (up to 99%) without any significant electronic or steric demands (Scheme 8.17). The difluoroketones 56 proved just as useful as substrates (Scheme 8.18). Of note, the parent alkaloid, quinine, as a catalyst did not give rise to any asymmetric induction. 

Addition and cycloaddition reactions. Henry reaction carried out in the presence of Cu(OTf)2 and 1 is a demonstration of the possibility in developing reaction that is electronically and sterically tunable. ... 

The nitroaldol (Henry) reaction provides 1,2-nitro alkanols under atom-economical proton transfer conditions, which allows for easy access to highly versatile 1,2-amino alcohols (Scheme 6) [31]. A number of catalytic systems have been devised to render this useful C-C bond-forming reaction asymmetric however, diastereoselectivity remained a longstanding problem, in particular for a ri-selective reactions [14, 32, 33]. syw-Selective reaction can be achieved by a monometalhc catalytic system as shown in Fig. 9a, where both an aldehyde and a nitronate coordinate to the metal center to give syn product due to steric repulsion [34—36]. To make the reaction proceed in fluft-selective manner, different strategy in catalyst design is required [37, 38]. Simultaneous activation of both the aldehyde and the nitronate in an anti-paraUel fashion can afford the anti-1,2-nitro alkanols preferentially (Fig. 9b). To attain the a ri-paraUel transition state, a heterobimetalhc catalyst offers a suitable... 

The catalyst screening experiments were performed in the asymmetric Henry addition of nitromethane (10 equiv.) to 4-nitrobenzaldehyde in the presence of DABCO (20mol %) as the base and (thio)ureas 157, 158, 163, and 170-175 (each 10mol% loading). After 12h in reaction time at room temperature and in THF as the solvent, the corresponding Henry adduct was obtained in excellent yields (99%) but with very low ee values (7-17%) nearly independently of the sterical hindrance of the axiaUy chiral backbone skeleton (e.g., 172 and 174 each 99% yield 11% ee). Thioureas appeared slightly more enantioselective (e.g., 163 83% yield, 33% ee 171 99% yield, 15% ee) than their urea counterparts probably due... 

A collision theory of even gas phase reactions is not totally satisfactory, and the problems with the steric factor that we described earfier make this approach more empirical and qualitative than we would like. Transition state theory, developed largely by Henry Eyring, takes a somewhat different approach. We have already considered the potential energy surfaces that provide a graphical energy model for chemical reactions. Transition state theory (or activated complex theory) refers to the details of how reactions become products. For a reaction fike... 

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