Aldol solvent-free

The isomerization of an O-silyl ketene acetal to a C-silyl ester is catalyzed by a cationic zirconocene—alkoxide complex [92], This catalysis was observed as a side reaction in the zirconocene-catalyzed Mukaiyama aldol reactions and has not yet found synthetic use. The solvent-free bis(triflate) [Cp2Zr(OTf)2] also catalyzes the reaction in nitromethane (no reaction in dichloromethane), but in this case there may be competitive catalysis by TMSOTf (cf. the above discussion of the catalysis of the Mukaiyama aldol reaction) [91] (Scheme 8.51). 

Catalysis in reaction systems with undissolved substrates and products is not restricted to biocatalysis. High yields in sobd-state synthesis, sohd-to-sohd reactions, and solvent-free systems have also been reported for aldol condensation, Baeyer-Villiger oxidation, oxidative coupling of naphthols, and condensation of amines and aldehydes [1, 2]. 

The Cannizzaro reaction, that is, the base-catalysed disproportionation of a carbonyl compound to an alcohol and a carboxylic acid, has gained some importance as an economically viable alternative to the reduction with borohydrides. However, the reaction is restricted to carbonyl compounds without any a-hydrogen, which do not undergo competing aldol reactions. Thus, mainly aromatic aldehydes are used for this kind of transformation. The protocols developed for microwave applications typically involve solvent-free conditions using alumina as the solid support. Under these conditions, a significant acceleration of the reaction was achieved. 

Yamamoto has recently described a novel catalytic, asymmetric aldol addition reaction of enol stannanes 19 and 21 with aldehydes (Eqs. 8B2.6 and 8B2.7) [14]. The stannyl ketones are prepared solvent-free by treatment of the corresponding enol acetates with tributyltin methoxide. Although, in general, these enolates are known to exist as mixtures of C- and 0-bound tautomers, it is reported that the mixture may be utilized in the catalytic process. The complexes Yamamoto utilized in this unprecedented process are noteworthy in their novelty as catalysts for catalytic C-C bond-forming reactions. The active complex is generated upon treatment of Ag(OTf) with (R)-BINAP in THF. Under optimal conditions, 10 mol % catalyst 20 effects the addition of enol stannanes with benzaldehyde, hydrocinnamaldehyde, or cinnamaldehyde to give the adducts of acetone, rerf-butyl methyl ketone (pinacolone), and acetophenone in good yields and 41-95% ee (Table 8B2.3). 

A variety of Brpnsted acid sources - benzoic acid, silica gel, 3 A molecular sieves - catalyse vinylogous aldol reactions of O-silyl dienolates, under solvent-free conditions.140... 

The indium trichloride-catalyzed Mukaiyama aldol reaction of 3-aminoketoesters with various silylenolethers gave under solvent-free conditions 1,3-amino alcohols with high stereoselectivity [36], Several Robinson annelation reactions have been carried out enantio-selectively using (S)-proline as a chiral catalyst [37]. Remarkably, the enantioselectivity was distinctly higher in the absence of solvent than in DMSO. 

Microwave irradiation of a mixture of cyclohexenones and ethyl acetoacetate adsorbed on the surface of solid lithium 5-(2)-prolinate leads to the stereoselective construction of bicyclo[2.2.2]octanone (69) systems through Michael addition and subsequent intramolecular aldolization (Ranu et al., 2000). Electron-rich aromatic compounds react with formaldehyde and a secondary amine under solvent-free condition and microwave irradiation in a microwave oven to produce amino ethylated products (70) in good to excellent yields (Mojtahedi et al., 2000). 

When aliphatic nitro compounds are used instead of aldehydes or ketones, no reduction occurs, and the reaction has been referred to as a Tollens reaction (see 16-43). However, the classical condensation of an aliphatic nitro compound with an aldehyde or ketone is usually called the Henry reaction or the Kamlet reaction, and is essentially a nitro aldol reaction. A variety of conditions have been reported, including the use of a silica catalyst, Mg—A1 hydrotalcite, a tetraalkylam-monium hydroxide,proazaphosphatranes, " or an ionic liquid.A solvent free Henry reaction was reported in which a nitroalkane and an aldehyde were reacted on KOH powder. Potassium phosphate has been used with nitromethane and aryl aldehydes. The Henry reaction has been done using ZnEt2 and 20%... 

Some aldol condensation reactions proceed more efficiently and stereoselectively in the ab.sence of solvent than in solution [18]. When the solvent-free aldol reaction is carried out in an inclusion complex with a chiral host complex, diastereo-and enantioselective reactions occur, although enantioselectivity is not high [18]. 

Loh et al. reported that InClj worked as an effective catalyst of aldol reactions of SEE in water [77]. Later, Kobayashi et al. reported different results [78] - hydrolysis of SEE is faster than the desired reaction in the InCls-catalyzed aqueous system the InCls-catalyzed reaction proceeds to some extent under solvent-free conditions InCls is an effective catalyst in micellar systems. 

One of the most studied processes is the direct intermolecular asymmetric aldol condensation catalysed by proline and primary amines, which generally uses DMSO as solvent. The same reaction has been demonstrated to also occur using mechanochemical techniques, under solvent-free ball-milling conditions. This chemistry is generally referred to as enamine catalysis , since the electrophilic substitution reactions in the a-position of carbonyl compounds occur via enamine intermediates, as outlined in the catalytic cycle shown in Scheme 1.1. A ketone or an a-branched aldehyde, the donor carbonyl compound, is the enamine precursor and an aromatic aldehyde, the acceptor carbonyl compound, acts as the electrophile. Scheme 1.1 shows the TS for the ratedetermining enamine addition step, which is critical for the achievement of enantiocontrol, as calculated by Houk. ... 

Loh et al have demonstrated the stereoselective synthesis of 1,3-amino alcohols based on the InCla-catalyzed Mukaiyama aldol reaction of a keto ester under solvent-free conditions. The high selectivity has been explained by the influence of a remote group present in the keto ester (Scheme 5.45). 

T pe of reaction C-C bond formation Reaction condition solvent-free Keywords aldol reaction, proline... 

Phosphoric acid immobilized on silica (H3P04/Si02) catalyst has been widely exploited over many years [128-130]. It has also been used as a reusable catalyst for solvent-free imino-aldol three-component coupling reaction in recent years [131]. 

Aldol reactions. Aldol products are obtained in good yields from reaction of ketones with glyoxylic acid monohydrate with assistance of ultrasound irradiation. Substrate-control (by 1,3- + 1,5-asynmietric induction) of the aldol reaction involving y-amino-a-ketoesters under solvent-free conditions is very effective.- With lithium dicyclohexylamide and InCl, the reaction of esters with aldehydes furnishes P-hydroxy esters, and that of a-bromo esters affords a,p-epoxy esters." These are typical Reformatsky and Darzens reaction products, respectively. 

Aldol reactions. Reaction between two aldehydes proceeds under solvent-free conditions. It is perhaps useful for the preparation of a-substituted cinnamaldehydes. 

Chemoselective, Solvent-free aldol Condensation Reactions... 

Raston. C.L. Scott. J.L. Chemoselective, solvent-free aldol condensation reaction. Green Chem. 2000. 2. 49-52. 

Fteproduced from GuiSena G, del Carmen Hita M. Nijera C, Vidzquez SF Solvent-free asymmetric direct aldol reactions organocatalysed by recoverable (SJ-binam-L-prolinamide. Tetrahedron Asymm 2007 18 2300-4. Copyright (2007). with permission from Elsevier. 

A highly efficient solvent-free asymmetric direct aldol reaction organocatalyzed by recoverable (S)-Binam-L-Prollnamldes. ESI-MS evidence of the enamine-iminium formation. J Org Chem 2008 73 5933-43. Copyright (2008), American Chemical Society. 

Reproduced with permission from Alma D, Alonso DA, N jera C. Prolinamides versus proiine-thioamides as recyclable catalysts in the enantbselective solvent-free inter- and intramolecular aldol reactions. Adv Synth Catal 2008 350 2467-72. Copyright (2008), Wiley. 

Reproduced from Herndndez JG, Garcfa-Ldpez V, Juaristi Solvent-free asymmetric aldol reaction organocatalyzed by (S)-prollne-contalnlng thiodipeptides under ball-milling conditions. Tetrahedron 2012 68 92-7. Copyright (2012), with permission from Elsevier. 

Reproduced with permission from Machuca E, Rojas Y, Juarlsti E Synthesis and evaluation of (S)-prolhe-contalnlng a. p-dipeptides as organocatalysts In solvent-free asymmetric aldol reactions under ball-milling conditions. Asian J Org Chem 2015 4 46-53. Copyright (2015), Wiley. 

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