Henry asymmetric

Ph (SbFe)2 Ph Ph TIO OTf Ph 84 Scheme 14 Catalytic asymmetric aza-Henry (nitro-Mannich-type) reactions... 

The nitroaldol reaction or Henry reaction is a powerful and highly versatile carbon-carbon bond-forming reaction, allowing a plethora of key molecular frameworks, such as p-hydroxynitroalkanes, 1,2-amino alcohols or a-hydroxy carboxylic acids to be synthesised in a straightforward manner. Therefore, the development of practical catalytic asymmetric versions of this reaction is still largely desirable. The first catalytic asymmetric nitroaldol reaction was reported in 1992, " but despite its long history, relatively few chiral ligands have... 

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Scheme 3 62 is an example of an asymmetric Henry reaction reported by Sasai et al.116 in 1993. The catalyst acts in a bimetallic manner. This multifunctional effect is further discussed in Chapter 8. 

Scheme 3-63 gives another example in which an asymmetric Henry reaction is involved in the synthesis of the /i-receptor-blocking drug (S )-propranolol. 

Gerard Uhommet was born in 1945 in Paris (France). He obtained his M.Sc. from the University of Paris in 1969. He carried out his Ph.D. studies under the supervision of Profs Pierre Maitte and Henri Sliwa at UPMC (P. and M. Curie University), Paris between 1970 and 1975. After a postdoctoral position at the East Anglia University in Norwich, UK, with Prof A.R. Katritzky (1976-1977), he accepted a position as Assistant Professor at UPMC, Paris. In 1985, he became Full Professor at the same university. His research interests include the development of new strategies sparing chiral auxiliaries for use in asymmetric and natural product synthesis. 

H7. Henry, P. S. H., The role of asymmetric rubbing in the generation of static electricity, Brit. J. Appl. Phys. Suppl. 2, S31 (1953). 

With a monomode CO2 laser, delivering a constant power on any rotational line of either the 10.4 jtx or the 9.4 n band, Bordfe and Henry studied the shape of Lamb dip profiles in CO2 which became asymmetric when two rotational lines were allowed to oscillate simultaneously, since the gains are tightly coupled by rotational thermalization. 

Palomo, C. Oiarbide, M. Mielgo, A. Unveiling reliable catalysts for the asymmetric nitroaldol (Henry) reaction. Angew. Chem. Int. Ed. 2004,43,5442-5444. 

Scheme 12.22 Asymmetric nitroaldol (Henry) reaction of various aldehydes (Pe-h) with nitromethane.

Reactions where NLE have been discovered include Sharpless asymmetric epoxi-dation of allylic alcohols, enantioselective oxidation of sulfides to sulfoxides, Diels-Alder and hetero-Diels-Alder reactions, carbonyl-ene reactions, addition of MesSiCN or organometallics on aldehydes, conjugated additions of organometal-lics on enones, enantioselective hydrogenations, copolymerization, and the Henry reaction. Because of the diversity of the reactions, it is more convenient to classify the examples according to the types of catalyst involved. 

As a true testament to the potential long-term impact of H-bonding activation, a number of ureas, thioureas, and acid catalysts are now finding broad application in a large number of classical and modem carbon-carbon bond-forming processes. On one hand, Johnston s chiral amidinium ion 28 was elegantly applied to the asymmetric aza-Henry reactions (Scheme 11.12d). On the other hand, chiral phosphoric acids (e.g., 29 and 30), initially developed by Akiyama and Terada, have been successfully employed in Mannich reactions, hydrophosphonylation reac-tions, aza-Friedel-Crafts alkylations (Scheme 11.12e), and in the first example... 

Fig. 7 Proposed role of cyclohexane-diamine thiourea 166 for the asymmetric aza-Henry reaction...

Scheme 6.128 Product range of 121-catalyzed asymmetric aza-Henry reactions between N-protected aldimines and nitromethane. The configurations of the products were not determined.

Scheme 6.146 Representative adducts obtained from the asymmetric Henry reaction between nitromethane and (hetero)aromatic aldehydes under bifunctional catalysis of C6 -thiourea-functionalized cinchona alkaloid 131.

Scheme 6.147 Mechanistic proposals for the 131-catalyzed asymmetric Henry addition of nitromethane to benzaldehyde. Preliminary model (A) Involving double hydrogen bonding and DFT-based model (B) supporting single hydrogen bonding to benzaldehyde and nitronate.

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... 

Scheme 6.166 Product range of the asymmetric Henry (nitroaldol) reaction of aldehydes with various nitroalkanes in the presence of (S,S)-configured catalyst 183.

Since a-branched aldehydes gave rather higher asymmetric induction (Scheme 6.166), Nagasawa et al. extended the biphasic strategy to the diastereoselective Henry reaction of nitromethane with enantiomerically pure (S)-configured N,N -dibenzyl protected a-amino aldehydes and a-hydroxy aldehydes protected as silyl ethers. The screening reaction (Scheme 6.169) demonstrated a match/mismatch... 

Scheme 6.168 Syntheses of 4-ep/-cytoxazone and cytoxazone utilizing guanidine-thioureas 183 and 186 for the initial asymmetric Henry reaction step.

Scheme 6.178 Typical products provided from the asymmetric aza-Henry addition of nitromethane to N-Boc-protected aldimines in the presence of saccharide thiourea 211 as bifunctional hydrogen-bonding catalyst.

Figure 6.64 Representative N-sulfinyl (thio)ureas evaluated for catalytic activity in the asymmetric aza-Henry reaction of N-Boc-protected benzaldimine with nitroethane affording model product 1.

Corey and colleagues applied their catalyst to the asymmetric Henry (nitro aldol) reaction using chiral aminoaldehydes and the short-step synthesis of an HIV protease inhibitor (Scheme 3.9) [26]. Interestingly, a newly generated asymmetric center is controlled by the chiral catalyst and nitrogen substituents. 

The catalytic asymmetric Henry reaction has been reviewed.141,142... 

The catalytic asymmetric Henry reaction has been reviewed.42 Mild and efficient enantioselective nitroaldol reactions of nitromethane with various aldehydes have been catalysed by chiral copper Schiff-base complexes yielding the corresponding adducts with high yields and good enantiometric excess.43,44... 

The asymmetric catalytic nitroaldol reaction, also known as the asymmetric Henry reaction, is another example of an aldol-related synthesis of high general interest. In this reaction nitromethane (or a related nitroalkane) reacts in the presence of a chiral catalyst with an aldehyde, forming optically active / -nitro alcohols [122], The / -nitro alcohols are valuable intermediates in the synthesis of a broad variety of chiral building blocks, e.g. / -amino alcohols. A highly efficient asymmetric catalytic nitroaldol reaction has been developed by the Shibasaki group, who used multifunctional lanthanoid-based complexes as chiral catalysts [122-125],... 

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