Henry reaction basicity

Sequential radical cyclizations are also featured in an efficient and clever synthesis of the cedrane framework 83 (see Scheme 15).30 Compound 81, the product of a regioselective Diels-Alder reaction between isoprene (79) and nitroethylene (80), participates in a nitroaldol reaction (Henry reaction) with 5-methyl-4-hexenal in the presence of a basic resin to give 82. Because the nitro group in... 

Recently, enantioselective organo-catalytic procedures for the aza-Henry reaction have been disclosed. The presence of either an acidic or a basic function appears to be a requisite of the catalyst. In fact, the condensation of ni-tromethane with M-phosphinoyl arylimines 72 is catalyzed by the chiral urea 85 derived from (R,R)-l,2-diaminocyclohexane and gives the product (R)-74 with good yield and moderate enantioselectivity (Scheme 15) [50]. The N-phosphinoyl substituent is determinant, as the addition of nitromethane to the N-phenyl benzaldimine failed and the reaction of the N-tosyl ben-zaldimine gave the expected adduct with quantitative yield but almost no... 

The Sowden homologation [21], based on the nitroaldol condensation (Henry reaction) [22] between the aldehydo sugar and nitromethane in basic medium, followed by the Nef decomposition [23] of the resultant nitronate in strongly acidic conditions, has been employed in a more limited number of cases than the cyanohydrin synthesis. A recent example in this area is shown by the stepwise homologation of (V-acetyl-D-mannosamine (11) into /V-acetylneuraminic acid (12) [24] (Scheme 4). Also, this procedure has found... 

The basic character of lanthanide alkoxides such as Lu3(Of-Bu)9 seem to effect aldol, cyanosilylation, aldol, and Michael reactions [111]. Complexes 2 and 22, abbreviated as LnMB (Ln = lanthanide, M = alkali metal, B = BR IOL) [112] were thoroughly studied in the catalytic, asymmetric nitroaldol reaction (Henry reaction eq. (10)) [113]. 

The Henry reaction is performed, in the presence of catalysts (organic or inorganic bases, quaternary ammonium salts, etc.), protic and aprotic organic solvents [161], water [162], supercritical fluids [163] or ionic liquids [164], Nitroalkenes can be obtained as by-products, via dehydration of p-nitroalcohols. Considerable efforts have been made to increase the yield and selectivity and to control the basicity of the medium and the reaction time. 

Non-activated y grade alumina for chromatography is sufficiently basic to promote hydrogen abstraction to rather acidic carbon acids (pKa<15) [19]. In such a way, numerous anionic condensations are described, for example, an aldolization [Eq. (10)] [20] leading to aurone, a basic compound in flower pigmentation, a Knoevenhagel reaction [Eq. (11) ] [21 ], or a case of a Henry reaction [Eq. (12)] [22]. 

The same basic principle of this catalytic cycle with slight modifications concerning the structure of several intermediates can also be proposed when using the improved, second generation catalysts of the LnLB type [11]. The Henry reaction with this type of catalysts together with detailed mechanistic considerations will be described in section 6. 

X = OH) act as very efficient bases for the Heck reaction and catalyze efficiently the Henry reaction with excellent yields and selectivities. The catalyst can be used both in batch and under flow conditions and can be directly reused several times with only a minor decrease in activity. The spent polymer can be easily regenerated simply by its treatment with a basic solution [363],... 

The Henry reaction is an aldol-type reaction between a nitroalkane and an aldehyde in the presence of a base. Since basic reagents are also catalysts for the aldol condensation, the nitroaldol reactions must be strictly controlled. An interesting alternative lies in the use of surfactants to perform the reaction in an aqueous medium [63], The Reformatsky reaction, which involves a-haloketones and aldehydes, can be mediated by zinc, tin or indium in water in the latter case the proportion of undesirable reduction products could be strongly reduced [64]. 

In their extensive efforts to devise a new strong nonionic base, Verkade and coworkers found that a highly basic dendrimer containing a PAPT base fragment could act as an efficient catalyst for Michael addition reactions, nitroaldol (Henry) reactions and aryl isocyanate trimerization reactions [42] (Figure 6.3). In view of the characteristic nature of this dendrimer, which has sixteen catalytic sites per molecule, the attachment of other superbase functionalities might also be attractive. 

From aliphatic 2-nitroalkanols, readily accessible via the Henry reaction,i3i the reduction by aluminum amalgam also gives hydroxylamines as intermediates, further reduced to amino alcohols.i mildly basic conditions permit the acylation of the amino group, and the amino alcohols can be conveniently isolated as the N-acetyl or benzoyl derivatives. 

Catalytic asymmetric nitroaldol (Henry) reactions of ketones lead to synthetically versatile chiral tertiary nitroaldols. Enantioselective nitroaldol reactions of a-keto esters have been achieved using chiral Cu and Mg complexes, and cinchona alkaloids [140]. However, there are no reports on the asymmetric synthesis of tertiary nitroaldols derived from simple ketones. Even for a racemic version, only a few methodologies with limited substrate scope are available. The difficulty arises from the attenuated reactivity of ketones and their strong tendency toward a retro-nitroaldol reaction under basic conditions. (S)-LLB catalyst was found suitable to promote retro-nitroaldol reaction and a kinetic resolution of racemic tert-nitroaldols was realized. (S)-LLB preferentially converted the matched (R)-enantiomer into ketone and nitromethane, whereas the mismatched (S)-enantiomer remained unchanged and was recovered in an enantiomerically... 

While these organocatalysts comprise a considerably broad stractural/functional spectrum, a common requirement for them to work efficiently in the Henry reaction appears to be the presence of (i) a basic unit to generate the nucleophilic nitronate species and (ii) some hydrogen bond donor sites capable of interacting with the acceptor carbonyl group. 

The enantioselective Henry reaction with ketones is challenging, owing to the attenuated reactivity of the ketone carbonyl group compared to the aldehyde carbonyl moiety and the high tendency of tertiary nitro-aldol adducts to undergo a retro-addition reaction under basic conditions [15], Stereoselective construction of... 

Since Takemoto first demonstrated the effectiveness of the bifunctional thiourea catalyst 25 in the aza-Henry reaction with imines, several chiral BB catalysts (27-34) have been reported for this reaction, all maintaining an amine as the basic unit and a thiourea group as the hydrogen bond donor (Figure 29.3). Table 29.3 shows representative data concerning the addition of nitromethane to N-Boc... 

Chiral ammonium betaines are a particular class of bifunctional BB-based catalysts that have been successfully applied in the aza-Henry reaction of N-Boc imines and a-substituted a-nitroesters [42]. The catalyst structure displays an intramolecular ion-pairing quaternary ammonium aryl-oxide and the mode of action may involve deprotonation of the pronucleophile by the basic anion to furnish and onium ion as its conjugate acid form. Catalyst loadings as low as lmol% produced the corresponding quaternary-tertiary aza-Henry adducts in excellent yields and enantioselectivities, albeit with low to moderate diastereoselectivities (Scheme 29.18). The lowest de s (up to 33%) were obtained with aliphatic N-Boc imines (R = CH2CH2Ph, -octyl). 

Sharma et al. reported on the synthesis and catalytic properties of bifunctional heterogeneous catalysts with basic and organometallic catalysts for efficient catalysis of two-step Sonogashira and Henry reactions [55]. With a solvent-assisted grafting method, two different catalytic groups— an organoamine and a palladium-organodiamine... 

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