Aldehydes and substitution

Tablet. 1,2-Disubstituted 3-Butenols by Diastereoselectivc Reaction of Aldehydes and Substituted Allylboronates ... 

Partially hydrogenated quinoline cores are also present in some important bioactive compounds. For example, the 4-aza-analogs of Podophyllotoxin, a plant lignan that inhibits microtubule assembly, revealed to be more potent and less toxic anticancer agents. In 2006, Ji s group reported a green multicomponent approach to a new series of these derivatives, consisting of the reaction of either tetronic acid or 1,3-indanedione with various aldehydes and substituted anilines in water under microwave irradiation conditions (Scheme 26) [107]. For this efficient and eco-friendly transformation, the authors proposed a mechanism quite similar to the one that was postulated for the synthesis of tetrahydroquinolines in the precedent section. 

The Lewis acid-catalyzed three-component reaction of dihydropyridines, aldehydes, and />-substituted anilines efficiently yields highly substituted tetrahydroquinolines in a stereoselective manner, through a mechanism believed to be imine formation followed by formal [4-1-2] cycloaddition (Scheme 41). The 1,4-dihydropyridine starting materials were also prepared in situ by the nucleophilic addition of cyanide to pyridinium salts, creating in effect a one-pot four-component reaction <20030L717>. 

Table 14.14 Critical structural features which can affect the carcinogenicity of aldehydes and substituted aldehydes,.

Substituted aldehydes and substituted amines also react for example, the sodium salt of a-naphthylamine 4-sulphonic acid when dissolved in water and shaken with an alcoholic solution of benzaldehyde yields sodium benzylidine naphthionate. 

The most important derivatives of this mixed type are those obtained by substituting, in alcohols, aldehydes, or acids, some other element or group. This gives us compounds known, in general, as substituted alcoholsj substituted aldehydes, and substituted acids. These three classes of mixed compounds will now be considered. The simplest group of substituted alcohols are the halogen alcohols. Of the halogen alcohols the simplest would be derived from methyl alcohol, e.g.,... 

Table 1 Diastereoselectivity in the Reactions of Aldehydes and Substituted Allyboronates...

Condensation of 1, aromatic aldehydes and substituted acetophenone in the presence of NH4OAc under MW irradiation in DMF gave the acridines 356 (R = Ar, R1 = H) instead of the expected 2,4-diaryl-7,7-dimethyl-l,4,5,6,7,8-hexahydroquinolin-5-one (07TL1369) (Scheme 70). 

RCO ) are obtained by oxidation of the aldehyde, and substitution occurs at the 2-position. ... 

All these reactions can be effected conveniently under mild conditions and at low temperatures. Thus the procedure is especially advantageous for the preparation of, / -unsaturated aldehydes and substituted glyoxals. A review of the reaction has been published by Krohnke, where he gives also experimental details.545 The Krohnke process also enabled Ried and Bender546 to succed in the first synthesis of a heterocyclic dialdehyde (2,3-thionaphthenedicarbaldehyde). 

The condensation of salicylaldehyde or its derivatives with various derivatives of ethyl acetate in the presence of piperidine led to the synthesis of coumarins 95 in 55-94% yields under solvent-free conditions using MWI. Similarly, the benzo analogs 96 were prepared in 75-82% yields from 2-hydroxy-1-naphthaldehyde within 3-lOmin (Scheme 19) (98JCR(S)468). However, naphtho[2,l-Z ]pyran-3-ones 96 were prepared in 58-67% yields from the same aldehyde and substituted acetic acids under MWI for 6-8 min but in the presence of DCC and using DMSO as a solvent (Scheme 19) (97JCR(S)178). 

In comparison to samarium and ytterbium salts, there were few examples for cerium, praseodymium, and other the rare earth metals catalyzed aldol reaction (214,215). In 2000s, Samarium salts, especially Sml2, have been used in versatile aldol reactions, for example, direct aldol of aldehydes and substituted oxi-ranyl ketones (216), nitro aldol reaction (217,218), intramolecular aldol reaction (219), and other aldol reaction of special carbonyl compounds (220-222). However, catalytic asymmetric samarium-catalytic aldol reaction was not reported so far. In the asymmetric version of the aldol reaction, ytterbium exhibited promising enantioinduction. In the first example of the asymmetric ytterbium-catalyzed aldol reaction, moderate levels of enantioselectivities were achieved (Scheme 56) (223). Subsequently, Mlynarski and co-workers improved enatioinduction ability of the ytterbium-catalyzed aldol reaction by using catalytic amount of Yb(OTf)3... 

Copper-iron-polyphthalocyanine [251,252] showed a specific catalysis for the oxidations of saturated aldehydes and substituted benzaldehydes with oxygen. The catalytic reaction was solvent dependent so that tetrahydrofuran, ethanol, acetonitrile, ethyl acetate and anisole inhibited benzaldehyde oxidation while oxidation occurred readily in benzene or acetone. Benzaldehyde was catalytically oxidized with copper-iron-polyphthalocyanine and oxygen to give a quantitative yield of a mixture of perbenzoic (61%) and benzoic (39%) acids. Reaction was carried out at 30 °C and atmospheric pressure of oxygen and exhibited no induction period. By contrast p-methyl and p-chlorobenzaldehyde had induction periods of 8 and 15 min respectively while no oxidation of p-substituted benzaldehydes was observed when the para-substituent was NO2, OH, OCH3, or N(CH3)2. 

Sathiyanarayanan et al. [31] developed a simple and efficient three-component domino reaction of y-butyrolactam (2-pynolidinone), aromatic aldehyde, and substituted thiophenol catalyzed by iodine for the synthesis of l-((phenylthio)(phenyl) methyl)pyrrolidin-2-one derivatives 8. The stability of the synthesized analogs was evaluated in stimulated gastric fluid (SGF) and bovine serum albumin (BSA Scheme 10.6). 

C02Me, etc.) have been prepared by bis-condensations between the appropriate pyrrole bis-aldehyde and substituted acetone l,3-dimethyl-2/f-cyclohepta[c]pyrrol-6-one (148 R = H, R = R = Me, X = H) was then converted into 6-ethoxy-l,3-dimethyl-2-aza-azulene, ... 

Five-membered heterocycles with one nitrogen atom can be prepared from azomethine ylide-type dipoles and alkynes or alkenes. Several solid-supported cycloadditions with maleimide as a dipolarophile have been reported. Trityl resin-bound maleimide captured azomethine ylides that were generated in situ from amino acid methyl esters and aldehydes, and substituted resin-bound pyrrolidines were obtained (Scheme 11.1). Traceless cleavage of the C—N bond between acid-sensitive trityl resin and the IV-unsubstimted cycloadduct was achieved with 50% trifluoroacetic acid. 

Chiral Brpnsted acids have also been shown to effectively catalyze the Mannich reaction between aldehydes, anilines, and enecarbamates [100]. Here, the application of enecarba-mates as nucleophilic species instead of ketones gives access to enantioenriched 1,3-diamines after subsequent reduction in situ with sodium cyanoborohydride. The potential of this approach was demonstrated by reacting various aromatic or aliphatic aldehydes and substituted enecarbamates with para-nitroaniline in the presence of the chiral phosphoric acid catalyst 150 (Scheme 11.34). 

---