Henry reaction catalyst

Kambe and Yasuda19 discovered the effectiveness of the fluoride as a Henry reaction catalyst. Since then, the use of diverse fluorides is a common method to catalyze nitro aldol condensations, since they provide mild conditions that are particularly convenient for sensitive products as carbohydrates. The most common fluorides are potassium fluoride20 and tetrabutyl ammonium fluoride.21 A recent example relates to the TBAF catalyzed addition of nitroethanol to the D-glucose derivative 18, to give nitro sugars 19 (Scheme 8).22... 

The amine-based Henry reaction catalyst was encapsulated via the interfacial polymerization of oil-in-oil emulsions. PEI was encapsulated by dispersing a methanolic PEI solution into a continuous cyclohexane phase. Upon emulsification, 2,4-tolylene diisocyanate (TDI) was added to initiate crosslinking at the emulsion interface, forming polyurea shells that contain free chains of PEI. The microcapsules crenate when dry and swell when placed in solvents such as methanol and dimethylformamide, suggesting a hollow capsule rather than a solid sphere formation. The catalyst loading was determined to be 1.6 mmol g . ... 

Type of reaction C-C bond formation Reaction conditions -Propanol, room temperature Synthetic strategy Enantioselective Henry reaction Catalyst l-Cu(OAc)2 complex... 

The Henry reactions of A, ALdibenzyl-L-phenylalaninal with nitroalkanes using 1.2 equiv of tetrabutylammonium fluoride (TBAF) as the catalyst proceed in ahighly stereoselective manner, as shown in Eqs. 3.82 and 3.83. This reaction provides rapid and stereoselective access to important molecules containing 1,3-diamino-2-hydroxypropyl segments, which are cenhal structural subunit of the HIV protease inhibitor amprenavir (in Scheme 3.21). 

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 aza-Henry reaction is the nucleophilic addition of nitroalkanes to imines to give nitroamine derivatives. This reaction was also studied with metal-based catalysts [164]. 

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... 

The Henry reaction is catalyzed in homogeneous solution with various catalysts, as shown in Eq. 3.1. 

A more effective catalyst for the Henry reaction is a polymer-supported base such as amberlyst A-21. Various P-nitro alcohols can he obtained with the help of amberlyst with or without solvent (Eq. 3.14).25 A recent report claims that amberlite IRA-420 (OH-form) or DOWEX-1 (OH-form) is more effective for the Henry reaction than amberlyst A-21.26 Poly-... 

Proazaphosphatrane, P(RNCH2CH2)3N, is an efficient catalyst for the Henry reaction, and various ketones give nitro-aldols by the reaction with nitromethane and other nitroalkanes (Eq. 3.20).21... 

Nitromethylation of aldehydes has been carried out in a one pot procedure consisting of the Henry reaction, acetylation, and reduction with sodium borohydride, which provides a good method for the preparation of l-nitroalkanes.16b 79 It has been improved by several modifications. The initial condensation reaction is accelerated by use of KF and 18-crown-6 in isopropanol. Acetylation is effected with acetic anhydride at 25 °C and 4-dimethylaminopyridine (DMAP) as a catalyst. These mild conditions are compatible with various functional groups which are often... 

The Michael addition of nitroalkanes to election-deficient alkenes provides a powerful synthetic tool in which it is perceived that the nitro group can be transformed into various functionalities. Various kinds of bases have been used for this transformation in homogeneous solutions, or, alternatively, some heterogeneous catalysts have been employed. In general, bases used in the Henry reaction are also effective for these additions (Scheme 4.18).133... 

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. 

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

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... 

Papai et al. selected as model reaction the addition of 2,4-pentanedione (acetylacetone) to trans-(R)-mtrostyvQnQ, catalyzed by the bifunctional thiourea catalyst shown in Scheme 6 [46]. The analogous Michael-addition involving dimethyl malonate and nitroethylene as substrates, and a simplified catalyst was calculated at the same level of theory by Liu et al. [47]. Himo et al. performed a density functional study on the related cinchona-thiouTQa catalyzed Henry-reaction between nitromethane and benzaldehyde [48]. 

Nitroaldol (Henry) reactions of nitroalkanes and a carbonyl were investigated by Hiemstra [76], Based on their earlier studies with Cinchona alkaloid derived catalysts, they were able to achieve moderate enantioselectivities between aromatic aldehydes and nitromethane. Until then, organocatalyzed nitroaldol reactions displayed poor selectivities. Based on prior reports by Sods [77], an activated thionrea tethered to a Cinchona alkaloid at the quinoline position seemed like a good catalyst candidate. Hiemstra incorporated that same moiety to their catalyst. Snbsequently, catalyst 121 was used in the nitroaldol reaction of aromatic aldehydes to generate P-amino alcohols in high yield and high enantioselectivities (Scheme 27). 

Recently, Takemoto and co-workers reported the use of bifunctional ihiourea catalyst 166 for the aza-Henry reaction of nitroalkanes to A -Boc imines [107, 108], Using a... 

Ooi has recently reported application of chiral P-spiro tetraaminophosphonium salt 37 as a catalyst for the highly enantio- and diasterioselective direct Henry reaction of a variety of aliphatic and aromatic aldehydes with nitroalkanes (Scheme 5.51) [92]. Addihon of the strong base KO Bu generates in situ the corresponding catalyhcally active triaminoiminophosphorane base A. Ensuing formation of a doubly hydrogen-bonded ion pair B positions the nitronate for stereoselective addition to the aldehyde. This catalyst system bears many similarities to guanidine base catalysis. 

Scheme 6.75 Proposed mechanism of the enantio- and diastereoselective aza-Henry reaction between N-Boc-protected aldimines and nitroalkanes in the presence of biflinctional catalyst 12 and catalyzed epimerization of the syn-adduct at increased temperature.

For the model Henry reaction between benzaldehyde and nitromethane a solvent dependency of the enantioselectivity was detected (e.g., CH2CI2 6% ee MeOH 49% ee THF 62% ee aU at rt). Under optimized reaction conditions concerning catalyst loading (10 mol% of 131), solvent (TH F), and reaction temperature... 

Scheme 6.169 Screening reaction to identify (R,R)-configured guanidine-thiourea 186 as matching catalyst for the anti-diastereoselective and enantioselective Henry reaction of (S)-a-amino aldehydes with nitromethane.

Utilizing 10mol% of (R,R)-guanidine-thiourea catalyst 186 under optimized biphasic condihons for the Henry reaction [224] of (S)-a-amino aldehydes with nitromethane furnished the corresponding nitroalcohols 1-6 in yields ranging from 33 to 82% and with excellent diastereoselechvities (up to 99 1 anti/syn) and enanhoselectivihes of the major isomer (95-99% ee) (Scheme 6.171) [328]. 

McQuade et al. [11] have pubhshed a nice synthesis using a microencapsulated nickel-based catalyst for promoting a Henry reaction based upon the work of Evans [12]. Torrens et al. have pubhshed a somewhat longer synthesis from D-mannitol bisacetonide [13]. 

Simoni, D., Rondanin, R., Morini, M., Baruchello, R. and Invidiata, F.P., 1,5,7-triazabicyclo 4.4.0 dec-l-ene (TBD), 7-methyl-TBD (MTBD) and the polymer-supported TBD (P-TBD) three efficient catalysts for the nitroaldol (Henry) reaction and for the addition of dialkyl phosphites to unsaturated systems, Tetrahedron Lett., 2000, 41, 1607. 

The amines 3 reported by Morao and Cossio also constitute neutral dendritic catalysts without metal sites they consist of a simple amine core functionalised with Frechet dendrons (Fig. 6.44) [74]. Such amines can catalyse the nitroaldol or Henry reaction [75] between aromatic aldehydes and nitroalkanes. Whereas neither the yield nor the stereoselectivity (syn/anti 1 1) of the reaction of p-nitro-benzaldehyde with nitroethane was found to change on use of different generations of dendritic catalysts, a distinctly negative dendritic effect was observed in the reaction of benzaldehyde with 3-nitro-l-propanol. Catalysts 3 a and 3 b gave... 

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],... 

Figure 3.39 a The structure and proposed mode of action of the modified Cinchona alkaloid catalyst b an example ofthe catalytic Henry reaction between benzaldehyde and nitromethane. 

Cyclohexanediamine-derived amine thiourea 70, which provided high enantio-selectivities for the Michael addition [77] and aza-Henry reactions [78], showed poor activity in the MBH reaction. This fact is not surprising when one considers that a chiral urea catalyst functions by fundamentally different stereoinduction mechanisms in the MBH reaction, and in the activation of related imine substrates in Mannich or Streclcer reactions [80]. In contrast, the binaph-thylamine thiourea 71 mediated the addition of dihydrocinnamaldehyde 74 to cyclohexenone 75 in high yield (83%) and enantioselectivity (71% ee) (Table 5.6, entry 2) [79]. The more bulky diethyl analogue 72 displayed similar enantioselectivity (73% ee) while affording a lower yield (56%, entry 3). Catalyst 73 showed only low catalytic activity in the MBH reaction (18%, entry 4). 

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