Propanal aldol condensation with

An alternative tandem Michael addition/aldol condensation for the synthesis of 3,5-diaryl-substituted phenols 121 employs, instead of 1-(2-oxopropyl)pyridinium chloride (112), l-(benzotriazol-l-yl)propan-2-one (119) in the presence of excess of NaOH in refluxing ethanol (equation 106) ". Under these conditions, several types of 3,5-diaryl-substituted phenols 121 have been obtained in 52-94% yield. The reaction proceeds by Michael addition of the enolate of 119 to the a,/3-unsaturated ketone 118 to afford intermediate 120, which then undergoes an intramolecular aldol condensation with elimination of benzotriazole. 

Give several examples of aldehydes or ketones that could be used in a "crossed" aldol condensation with propanal. 

Mixed aldol condensations can be effective only if we limit the number of reaction pos sibilities It would not be useful for example to treat a solution of acetaldehyde and propanal with base A mixture of four aldol addition products forms under these condi tions Two of the products are those of self addition... 

Propane, 1-propanol, and heavy ends (the last are made by aldol condensation) are minor by-products of the hydroformylation step. A number of transition-metal carbonyls (qv), eg, Co, Fe, Ni, Rh, and Ir, have been used to cataly2e the oxo reaction, but cobalt and rhodium are the only economically practical choices. In the United States, Texas Eastman, Union Carbide, and Hoechst Celanese make 1-propanol by oxo technology (11). Texas Eastman, which had used conventional cobalt oxo technology with an HCo(CO)4 catalyst, switched to a phosphine-modified Rh catalyst ia 1989 (11) (see Oxo process). In Europe, 1-propanol is made by Hoechst AG and BASE AG (12). 

II reaction under similar conditions at temperatures between 80 and 100°C and with a four-fold excess of 2-methylpentanal (to compensate for the low solubility), the selectivity for the Aldol II product (80%) was 20% higher in [BMIMJEF NaOH than in the water/NaOH system, both at 100% propanal conversion. The increased selectivity was attributed to the higher solubility of the reactant 2-methylpentanal in the ionic liquid phase than in the water phase. The higher solubility of 2-methylpentanal effectively suppressed the self-aldol condensation in the ionic liquid. 

Also, the primary amine moities of polar lipids catalyze the aldol condensation of Cm-Cig aldehydes resulting from plasmalogen hydrolysis, thus forming a,3-unsaturated aldehydes (l2t). Phosphatidyl ethanolamine reacted with propanal and n-hexanal forming phosphatidyl l-(2-hydroxyethyl)-2-ethyl-3,5-dimethyl pyridinium, and phosphatidyl-1-(2-hydroxy ethyl)-2-hexyl-3,5-dipentyl pyridinium, respectively (125). The peridinium ring is formed by the reaction between one mole of amino-N of phosphatidyl ethanolamine and three moles of n-alkanals. The same reaction took place in the synthesis of substituted pyridines by condensation of carbonyl compounds with ammonia (126, 127). 

One of the most efficient methods for the generation of 2,5-dideoxy-2,5-iminogalactitol 16 relies on the fuculose-1-phosphate aldolase-catalyzed aldol condensation of 2-azido-3-hydroxypropanal with dihydroxyacetone monophosphate (Scheme 13.17). The same method, applied to (2/ )-2-azidopropanal R)-V7 and to (25 )-2-azido-propanal (5 )-17, allows for the preparation of 2,5,6-trideoxy-2,5-imino-D-allitol 18 and 2,5,6-trideoxy-2,5-imino-L-talitol 19, respectively [22]. 

C13H24O, Mr 196.33, df 0.900-0.906, rag> 1.470-1.475, is a colorless liquid with a woody, tenacious sandalwood odor with a slight musk nuance. It is prepared by sequential aldol condensation of campholenaldehyde (2,2,3-trimethyl-3-cyclopentenea-cetaldehyde, obtained by epoxidation of a-pinene and rearrangement of the epoxide) with propanal, hydrogenation and reduction [106]. 

Another route to the acetoxyaldehyde 73 comprises selective aldol condensation (Scheme 8). Acetoxyacetaldehyde (78) was reacted with propanal (79) in the presence of equimolar amounts of acetic acid and 40% aqueous dimethylamine. Separation of the catalyst and fractional distillation of the crude product provided (Ej-acetoxyaldehyde 73 in 42-63% yield [26]. 

U.S. production of w-butanol has increased to 600 kt per annum, largely for conversion to unsaturated esters and saturated ester and ether solvents, while 2-ethylhexanol (about 300 kt per annum in the U.S., but much higher in Europe with exports at 250 kt per annum) is used mainly for the phthalate ester as a plasticizer for PVC. The n- and iso-butyraldehydes are also subjected to aldol condensation/crossed Cannizzaro reactions with formaldehyde, to give the polyols trimethylol-propane (2, 2-bishydroxymethyl-l-butanol) and neopentyl glycol (2,2-dimethyl-1,3-propanediol). 

Furthermore, Heck [9], aldol [10], epoxidation [11], hydrogenation [12], cyclo-propanation [13], Mukaiyama aldol condensation [14], and oxidative kinetic resolution [15] batch reactions have also been successfully performed with SILP systems. 

Chiral (E)-enolethers. A degassed soln. of (5R)-5-cyclohexyl-2-ethenyl-l,3-dioxolan-4-one (2 1 cisjtrans) in THF added to ca. 1 eq. of a suspension of bis(l,5-cycloocta-diene)nickel(0) in the same solvent under N2, stirred until the complex dissolved (10 min), after 3h the resulting rust-coloured precipitate collected, suspended in methylene chloride, treated with MejSiCl, and stirred for 30 min intermediate 7c-allylnickel complex (Y 78%), in benzene treated with DMF and 5 eqs. 1-iodo-propane, irradiated with a sunlamp (GE 275 W Model RSW) for 2,5 h at 10°, stirred for a further 3 h, diluted with pentane to precipitate nickel halide, and stirred for a further 4 h product (Y 82% E/Z 9 1). Subsequent treatment with acetals afforded 2-p-alkoxy-l,3-dioxolan-4-ones with asym. induction, thereby providing an alternative to asym. aldol condensation. F.e. inch reaction with ar. and a,P-ethylene-bromides s. D.J. Krysan, P.B. Mackenzie, J. Am. Chem. Soc. 110, 6273 (1988). 

While the preparation of 12 was secured, the preparation of the dienyl side chain 21 was undertaken according to a biomimetic strategy using an aldol condensation of enal 19, which was synthesized from p-nitrobenzaldehyde and propanal. Since this transformation worked superbly for accessing -19, it was tempting to produce , -dienal 23 by iteration, a procedure that was actually described by Suzuki with modest efficiency (Scheme 17). Despite numerous attempts from Matthias to enhance the process, dienal 23 could not be obtained in yield higher than 22%. 

What happens if we try to carry out an aldol condensation between the enolate of one aldehyde and the carbonyl carbon of another In such a situation, called crossed aldol condensation, mixtures ensue, because enolates of both aldehydes are present and may react with the carbonyl groups of either starting compound. For example, a 1 1 mixture of acetaldehyde and propanal gives the four possible aldol addition products in comparable amounts. 

Aldehyde enolates present another problem. They tend to give selfcondensation before an electrophile can be added. This may be solved again by use of imine enolates or A,A-dimethylhydrazones, which are themselves of low electrophihcity and allow good crossed aldol condensations and alkylations. For example, the terf-butyl imine of propanal was converted to the enolate with LDA and used in a crossed aldol condensation (Eq. 7.16) [30]. 

Scheme 17.7 Key mechanistic possibilities in proline-catalyzed self aldol condensation between two molecules of propanal. Reproduced from Reference [35] with permission from Wiley-VCH Verlag GmbH.

One of the first careful studies of the influence of chirality proximal to ketone enolates is illustrated in eq. [95] (113). Condensation of the enolate 126 (M = Li) with propanal (THF, -100 C) afforded a modest bias for the (5,i )-diastereomeric aldol adduct 127 (127 128 = 57 43). The influence of the metal center in this condensation has recently been examined. The boryl enolate 126 [M = B(n-C4H9)2l afforded a ratio 127 128 = 64 36 in pentane (-78°C) (6a, 113). Similar studies designed to probe the dependence of diastereoface selection on metal enolate structure have been carried out with metal enolates 129 (eq. [96], Table 32). 

Stereochemically controlled synthesis of this subunit, which contains five stereogenic centers, is important to an efficient bleomycin synthesis. (2S,3S,4i )-4-(/er/-Butoxycarbonyl-amino)-3-hydroxy-2-methylpentanoic acid (15) was obtained via a stereoselective syn aldol addition of a boron Z-enolate with (27 )-2-(tert-butoxycarbonylamino)propanal (Scheme 4). Similarly, the L-threonine subunit 18 was prepared by diastereoselective syn aldol addition of an N- acy I ox azo I i di n one stannous Z-enolate with acetaldehyde. The bithiazole unit 19 was prepared using a direct DCC-promoted condensation of 3-(methylsulfanyl)propylamine. Convergent access to tetrapeptide S was obtained by coupling of acid 15 and deprotected 18 to give dipeptide 20, followed by further coupling with the bithiazole 19 to ultimately give tetrapeptide S (21). 

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