Henry reaction utility

The synthetic utility of the Henry reaction is shown in Scheme 3.1, where (3-nitro alcohols are converted into (3-amino alcohols, amino sugars, ketones and other important compounds. 

The nitroaldol (Henry) reaction has been recognized as a powerful synthetic tool and has also been utilized in the construction of numerous natural products and other useful compounds. As shown in Scheme 1, we succeeded in realizing the first exam-... 

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

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]. 

As with the Henry nitro-aldol condensation, the modified Dakin-West acylation is primarily used for synthesis of trifluoromethyl ketones, although there are several examples of its use in the synthesis of fluoromethyl ketones (Table 3).[31314 The modified Dakin-West reaction utilizes fluoroacetic anhydride (or other appropriate anhydrides) to form an anhydride, which then undergoes cyclization, activation of the a-carbon, and acylation at the a-carbon the precise details of this method will be discussed in Section 15.1.4.3.1. 

Commercially available TBD supported on polystyrene (PS-TBD) was utilized to promote the Henry reaction (Scheme 3.10). ... 

Abstract The possible utilization of room temperature ionic liquids (RTILs), instead of volatile organic compounds (VOCs), in the electrochemical procedures of organic synthesis has been discussed. The synthesis of p-lactams, the activation of carbon dioxide and its utilization as renewable carbon source and the carbon-carbon bond formation reactions via umpolung of aldehydes (benzoin condensation and Stetter reaction) and via Henry reaction have been selected as typical electrochani-cal methodologies. The results, related to procedures performed in RTILs, have been compared with those performed in VOCs. The double role of RTILs, as green solvents and parents of electrogenerated reactive intermediates or catalysts, has been emphasized. 

However, structural modification of the BINOL ligand system also plays an important role with regard to stereoselection in the asymmetric Henry reaction. Improved enantioselectivites were obtained using a number of (P)-BINOL derivatives 8 (3 mol equiv) in which the 6,6 -positions were substituted [21 ]. Their utility as asymmetric catalysts was assessed using the nitroaldol reaction of ni-tromethane with hydrocinnamaldehyde 1. Enantioselectivities up to 88% ee accompanied by chemical yields up to 85% were obtained using 3.3 mol % of various catalysts 9 and 10 equiv of nitromethane (-40 °C, 91 h) (Scheme 4). 

There are several important general reviews on the utility of nitro aliphatic compounds and the Henry reaction in organic synthesis. " Several of these are quite recent reviews and give further evidence for renewed interest in this area of chemistry. 

More recently, the use of high pressure with tetra-n-butylammonium fluoride as catalyst allowed these reactions to be accomplished with cyclic ketones. Thus, the Henry reaction of nitroalkanes with 3- and 4-methylcyclohexanones in THF at 30 C and 9 kbar (1 bar = 100 kPa) afforded fair to high yields (60-90% after 4 d) of the corresponding nitro alcohols, while with 2-methyIcyclohexanones it was possible to obtain addition products, although in moderate yields. These facts explain the modest utility of the Henry reaction as a chain-lengthening reaction when the carbonyl component is a ketone, but also show the difference in reactivity of aldehyde and ketone C==0 groups with respect to nitromethane, primary and secondary nitroalkanes in the presence of a base as catalyst. Such a difference in reactivity can be considered as the most evident chemoselectivity of this reaction. 

Although the Henry reaction has been known for over 90 years and is considered as a classic carbon-carbon bond-forming process, its utilization has so far been limited to simple nitroalkanes and the more... 

Syntheses of isomeric 3-acetamido-2,3,5-trldeoxy-L-hexopyranoses, utilizing the Henry reaction for coupling 4-nitro-butane-l,2-dlol and 2-oxypropanaL derivatives, are covered in Chapter 9. 

The utility of this method also stems from the fact that the nitro group enables C—C bond formation prior to the rearrangement. Michael addition of the anion derived from 276 to methyl vinyl ketone led to allylic nitro compound 277, which rearranged to allylic alcohol 278 in hi yield and excellent diastereoselectivity. Meanwhile, a single diastereomer of the bicyclic framework 280 was available under thermodynamic control from nitro aldehyde 279 via reversible Henry reaction, and transposition of the allylic nitro stereocenter to allylic alcohol 281 resulted from the suprafacial nature of the ensuing [2,3]-rearrangement. 

The novel, chiral A(-phosphoryl imine (45) has been successfully utilized in the asymmetric aza-Darzens and the asymmetric aza-Henry reactions... 

A report out of the Jorgensen laboratory further expanded the scope of copper-catalyzed aza-Henry reactions [50]. This report utilized chiral molecular recognition by combination of a chiral Cu(II) Lewis acid and chiral amine bases (organocatalysts) to catalyze the addition of tertiary nitro compounds (169) to an... 

The Henry reaction, or nitroaldo reaction, is one of the classic carbon-chain formation methods utilized in organic synthesis. It involves the condensation of nitroalkanes with aldehydes or ketones in the presence of bases (often catalytic amount) to afford the mixtures of diastereomeric 2-nitroalcohols, which in turn can be converted into other useful synthetic intermediates, such as 2-aminoalcohols, a-hydroxyketones, homologous ketones, and perhaps most importantly, nitroalkenes through various functional transformations. 

Connon introduced binaphthyl-derived bis-thiourea 31 and demonstrated that it could catalyze the addihon of N-methyhndole to various nitroalkenes, including those incorporating P-aliphahc substituents, although the enantioselectivity was generally moderate (Scheme 7.56) [84]. The utility of 31 was also proven by Wulff through use with a sub-catalytic amount of triethylamine for stereoselectively facilitating the aza-Henry reaction of nitroalkanes with N-Boc imines [85]. 

A dihydroquinidine-derived chiral thiourea (DHQD-30), which demonstrated significantly better stereocontrol than other cinchona alkaloids, was utilized in the aza-Henry reaction with nitroalkanes and aldimines by Schaus and coworkers (Scheme 13.8) [26]. The utility of the nitroethane pronucleophile conveniently offers a tertiary stereogenic center in the P-nitroamine product 32. The methodology is also conveniently applicable to novel a,P-unsaturated aliphatic imines 29, which are difficult substrates in asymmetric conjugate addition reactions. Similar reaction conditions can be appHed towards to the use of dimethyl malonates as pronucleophiles that generate adducts in high enantioselectivity, which then convert smoothly into P-amino esters under the Nef conditions. 

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