Aldehyde-mediated condensation

A.2.3 Anthocyanin-Flavanol and Anthocyanin-Anthocyanin Aldehyde-Mediated Condensation Reactions... 

Finally, reactions of flavonoid and nonflavonoid precursors are affected by other parameters like pH, temperature, presence of metal catalysts, etc. In particular, pH values determine the relative nucleophilic and electrophilic characters of both anthocyanins and flavanols. Studies performed in model solutions showed that acetaldehyde-mediated condensation is faster at pH 2.2 than at pH 4 and limited by the rate of aldehyde protonation. The formation of flavanol-anthocyanin adducts was also limited by the rate of proanthocyanidin cleavage, which was shown to take place at pH 3.2, but not at pH 3.8. Nucleophilic addition of anthocyanins was faster at pH 3.4 than at pH 1.7, but still took place at pH values much lower than those encountered in wine, as evidenced by the formation of anthocyanin-caffeoyltartaric acid adducts, methylmethine anthocyanin-flavanol adducts,and flavanol-anthocyanin adducts. The formation of pyranoanthocyanins requiring the flavylium cation was faster under more acidic conditions, as expected, but took place in the whole wine pH range. Thus, the availability of either the flavylium or the hemiketal form does not seem to limit any of the anthocyanin reactions. 

Stereoselective routes to the lactone precursors of the 1-hydroxyethylene isosteres using a titanium-mediated condensation has been reported by both Shibuya and co-workers1 and DeCamp et al. 19 The former method (Scheme 9) features the reaction between (2S)-2-dibenzylamino aldehydes and optically active dichloroisopropoxytitanium ester homo-enolates to provide the desired lactone with high erythro selectivity. Then, the lactone is opened by treatment with an amine and trimethylaluminum to give the 1-hydroxyethylene isostere. The experimental details of DeCamp et al. s high yielding and stereoselective synthesis 19 of lactone 8 (Scheme 10) is discussed in Section 10.6.2.2. 

The acid-mediated condensation of 2-naphthol with aliphatic or aromatic aldehydes can proceed under solvent-free conditions or in dichloroethane to give 14-alkyl/aryl-14//-dibcnzo[tf1/]xanthenes 167 in excellent yield (Equation 78) <2005SL955>. Sulfamic acid can also effectively catalyze the condensation of 2-naphthol with aromatic aldehydes either at 125 °C or under microwave irradiation to yield 14-aryl-14//-dibenzo[tf,/]xanthcncs in high yield (92-96%) <2005TL8691>. 

The acid-mediated condensation between 3,4-dienals (allenic aldehydes) and primary amines provided an entry to 2-thio-substituted pyrroles <07OL1445>. 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-mediated condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

Because these reactions involve the direct acid-mediated condensation between an aldehyde and a pyrrolic precursor, they bear direct analogy to the Rothemund-Adler-type procedures used to prepare tetraarylporphyrins, as well as to the... 

Transition-metal mediated condensation of esters and aldehydes is known. The reaction of a thioester and an aryl aldehyde with TiCLi—NBU3, for example, gave a p-hydroxy thioester with good syn selectivity. Selenoamides [RCH2C(=Se)NRy react with EDA and then an aldehyde to give p-hydroxy selenoamides. ... 

The aldol-type reaction of a-bromo ketones with aldehydes, mediated by CrCh, has been studied by Dubois and coworkers. The reaction is carried out by addition of (241 equation 80) to a solution of (242) and CrCh in THF. The reaction proceeds with high levels of syn selectivity with bulky bromo ketones (241), independent of the substrate aldehyde used (Table 11, entries 1-6). However, the reaction is stereorandom with bromoacetophenone (entry 7) and selectively anti with 2-bromocyclohexanone (entry 8). No explanation of the stereoselectivity has been advanced, but the reaction is believed not to proceed via a simple chromium enolate since no condensation reaction is obtained by addition of (242) to a solution of (241) and CrCh. Moreover, Nozaki and coworkershave demonstrated that chro-mium(II) chloride treatment of 1-bromocyclododecanone followed by treatment with either methyl iodide or TMS-Cl produces only cyclododecanone. 

The yeast-mediated condensation of benzaldehyde with acetaldehyde is of particular interest since it represents one of the first industrially useful microbial transformations, with the acyloin produced being subsequently converted chemically to o-ephidrine. Other illustrations of synthetic value are the yeast-induced condensation of aldehyde (4a,b) with fermentatively generated acetaldehyde. The initially formed acyloins (5a,b) are not isolated but are further reduced, again with enantiotopic specificity, to give the pheromone synthon (6a R = 3-styryl) and the a-tocopherol chromanyl moiety precursor (6b R = 2-propenylfuran) respectively (Scheme 3). ... 

Alternatively, epoxy esters may be prepared via the Darzens reaction, which involves base-mediated condensation of a-chloro esters with aldehydes or ketones. ... 

DCC-mediated condensation of hydroxy aldehyde 240 and acid 268 gave the aldehyde ester 269 (70%). An intramolecular olefination followed by chromatographic separation of the desired C-8 diastereomer led to the isolation of the 16-membered ring macrocycle 270 in 20% yield. Desilylation, oxidation, and cyclization then afforded a 47% yield of y-lactone 271. Acylation of the C-3 hydroxyl group was followed by reduction of the y-lactone and C-9 carbonyl. 

A final propargylic alcohol preparation involves reaction of a fluorinated vinyl phosphonate with aldehydes, mediated by a mixture of TBAF and (Me Si)2O (Scheme 56).111 The reaction occurs via elimination of FP(0)(0Et)2 from (36) to form the corresponding acetylene, which can then condense with the aldehyde after deprotonation by Me SiO. ... 

BF3-OEt2 reverses the usual anti selectivity observed in tbe reaction of crotyl organometallic compounds (based on Cu, Cd, Hg, Sn, Tl, Ti, Zr, and V, but not on Mg, Zn, or B) with aldehydes (eq la) and imines (eq lb), so that homoallyl alcohols and homoallylamines are formed, respectively. " The products show mainly syn diastereoselectivity. BF3-OEt2 is the only Lewis acid which produces hydroxy- rather than halo-tetrahydropyrans from the reaction of aUyl-stannanes with pyranosides. The BF3-OEt2 mediated condensations of y-oxygenated allylstannanes with aldehydes (eq Ic) and with activated imines (eq Id) affords vicinal diol derivatives and 1,2-amino alcohols, respectively, with syn diastereoselectivity. The activated imines are obtained from... 

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