A Henry reaction

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

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... 

Reaction of nitromethane and monosaccharide-derived dialdehydes is a useful tool that has been broadly used for the preparation of nitro and amino sugars, and carbocycles.30 Dialdehydes can easily be obtained by oxidative cleavage of conveniently protected monosaccharides with sodium periodate. Their subsequent Henry reaction with a nitroalkene, commonly nitromethane, usually gives isomeric mixtures that require the isolation of the major isomer.31 Thus, treatment of the D-ribose derivative 27 with sodium periodate gave dialdehyde 28, which was subjected to a Henry reaction with nitromethane, to afford nitrosugar 29 as an epimeric mixture (Scheme 11).32... 

This sequence involves a Henry reaction of 41 with nitromethane followed by a dehydration of the resulting acyclic D-heptitol derivative 42 and a Michael intramolecular addition of the resulting nitroolefin 43. 

The Henry reaction of nitro sugars and sugar aldehydes is a powerful tool for the formation of C-glycosydic bonds. A recent example is the preparation of disaccharide precursor 60 stated in Scheme 21.45 It involves a Henry reaction of nitro sugar 58 and aldehyde 59 in acetonitrile in the presence of catalytic potassium fluoride, to give nitro alcohol 60, a precursor of the corresponding C-disaccharide. 

For example, the 0,C-trisaccharide 153 was obtained by a Henry reaction of nitro disaccharide 151 and sugar aldehyde 150 followed by the dehydration of (3-nitro alcohol 152 and reduction of the resulting nitroolefin, to give nitro sugar 153. Finally, a radical elimination of the nitro group afforded the target 154 (Scheme 47).105... 

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]. 

One possible starting materia] preparation A Henry Reaction followed by trapping with Ac t) and elimination of the resultant acetate. 

In the synthesis we should not wish to make 21 as it would cyclise and, in any case, we d rather reduce nitrile, nitro and alkene all in the same step by catalytic hydrogenation. The very simple method used for the conjugate addition is possible only because of the slow aldol reaction of the hindered aldehyde 24. The aldol 25, also called a Henry reaction, needs a separate dehydration step but the three functional groups in 26 are reduced in one step in good yield.7... 

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]. 

Reaction of aldehydes with methyl 3-nitropropanoate in a Henry reaction, leads throngh to bntenolides. A 3(2 0-furanone can be neatly prodnced by the intramolecular displacement of bromide from a 1 -bromo-2,4-dione. ... 

Boruah et al. reported a facile and convenient synthesis of pyridines 16 from P-formyl enamides 17 under microwave irradiation employing a Henry reaction <04SL1309>. The author postulates that nitromethane reacts with the formyl group, followed by dehydration and subsequent cyclization and aromatization to yield the nitro-pyridine 16. 

Recently, the group of Boruah achieved the synthesis of annelated pyridines from yfi-formyl enamides via a Henry reaction in a one-pot process [186]. Under the action of microwave irradiation, in the presence of a base, for example pyrrolidine, morpholine or piperidine, yields from 80 to 90% were obtained after 8 to 10 min (Scheme 10.96). 

Kulhanek et al. have prepared optically pure (lR,7S)-4-[2-(diphenylphos-phanyl)phenyl]-l,10,10-trimethyl-3,5-diazatricyclo [5.2.1.02.6] deca-2(6),3-diene (219). The barrier to rotation around the C2-aryl bond is probably smaller than in 218 and the occurrence of diastereomeric forms was not mentioned (08TA2462). 219 was used as a ligand in a Henry reaction and led to moderate ee. 

The base-catalyzed solid-phase condensation through a Henry reaction of jS-formyl enamides 143 with nitromethane in the presence of pyrrolidine produced pyridine derivatives 148 in 80 90% yields under MWI for 8-10 min. The conventional heating in toluene for 8-10 h gave lower yields (62-74%). The mechanism... 

FIGURE 4.18 Three model reactions catalyzed by the MSN catalysts aldol reaction (a), Henry reaction (b), and cyanosilylation (c). (Figure modified from Reference 35.)... 

A library of 16 C2-symmetric modular chiral BINOL-oxazoline Schiff base cop-per(II) complex catalysts have been generated in situ in a one-pot, three-component manner. Yields and ee of up to 98% were obtained in a Henry reaction under mild conditions. ... 

Recently, a Henry reaction between aldehydes (e.g., benzaldehyde 26) and nitroalkanes (e.g., nitromethane 27) catalyzed by cyclophane-based thiourea 28 was reported (Scheme 3.27). ... 

A Henry reaction in aqueous media gives iyn- 0-nitroalcohols under very mild conditions reactions take a day or two, using phosphate buffer at neutral pH and ambient temperature.Aromatic aldehydes work with comparable yields to aliphatics. 

Three closely related phenanthrolinylquinine ligands were tested for their ability to coordinate copper(II).i One did not form a complex, another gave an unexpected five-coordinate mode and the third catalysed a Henry reaction in high ee, being able to activate both aldehyde and nitroalkane. 

This synthetic feat relies on an asymmetric Michael/Michael/Henry tandem sequence, resulting in a formal [24-24-2] cycloaddition. The generation of a chiral copper enolate, which undergoes two successive Michael additions on two nitroalkenes followed by ring closure with a Henry reaction, generates the expected adduct in a highly enantio- and diastereoselective manner (Scheme 7.14). 

A similar strategy was used in the synthesis of piperidine derivatives when the y-nitroaldehydes 91 were reacted with an imine through a Henry reaction followed by intramolecular hemiaminalization (Scheme 1.36). An efficient asymmetrical... 

Compounds containing nitro groups are very usefiil intermediates for the synthesis of natural products and other biologically active molecules. In this respect, p-nitroalka-nols, easily obtained via the nitroaldol (Henry) reaction, provide efficient access to valuable compounds such as 3-amino alcohols. Ramstrom et al. have performed the DKR of several (3-nitroaIkanols combining a Henry reaction and a lipase-catalyzed transesterification (Scheme 57.15). Seeing as the nitroaldol reaction is... 

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