Aryl aldehyde

LAPWORTH (BENZOIN) Condensation Condensation of two molecules of aryl aldehydes fo an alpha-hydroxy ketone catalysed by CN (via cyanohydnns). 

In an approach to opioid receptor ligands,diazabicyclononanones were prepared in a double Petrenko-Kritschenko reaction. Diester 76, in the presence of methylamine and aryl aldehydes, was converted to piperidone 77. This was immediately resubmitted to the reaction conditions however, in this iteration formaldehyde replaced the aryl aldehyde component. The outcome of this reaction produced 78 which was further investigated for its use in rheumatoid arthritis. 

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

Installation of a different side chain completely alters the pharmacological profile leading to a new class of muscle relaxants. The synthesis begins with copper(II)-promoted di-azonium coupling between furfural (j ) and 3,4-dichlorobenzene-diazonium chloride (15) to give bi aryl aldehyde Next, condensation with 1-aminohydantoin produces the muscle relaxant clodanolene (17). ... 

The first reported chiral catalysts allowing the enantioselective addition of diethylzinc to aryl aldehydes in up to 60% cc were the palladium and cobalt complexes of 1,7,7-trimethylbicy-clo[2.2.1. ]heptane-2,3-dione dioxime (A,B)3. A number of other, even more effective catalysts, based on the camphor structure (C K, Table 26) have been developed. 

Since amines, unlike alcohols, do not react with dialkylzincs but may coordinatively bind to the zinc atom, the dilithio salt of 2,5-diisopropylpiperazine is a more potent catalyst than the piperazine itself, presumably due to the greater nucleophilic power of the dianion10. Dimethylzinc reacts rather slowly with aryl aldehydes and although the product is obtained in high enantiomeric excess, the chemical yield is low10. 

Enolizable compounds can be used for Meerwein reactions provided that the keto-enol equilibrium is not too far on the side of the ketone for example, P-dicar-bonyl compounds such as acetylacetone are suitable (Citterio and Ferrario, 1983). The arylation of enol esters or ethers (10.12) affords a convenient route for arylating aldehydes and ketones at the a-carbon atom (Scheme 10-48). Silyl enol ethers [10.12, R = Si(CH3)3] can be used instead of enol ethers (Sakakura et al., 1985). The reaction is carried out in pyridine. 

Another arylation reaction which uses arenediazonium salts as reagents and is catalyzed by copper should be discussed in this section on Meerwein reactions. It is the Beech reaction (Scheme 10-49) in which ketoximes such as formaldoxime (10.13, R=H), acetaldoxime (10.13, R=CH3), and other ketoximes with aliphatic residues R are arylated (Beech, 1954). The primary products are arylated oximes (10.14) yielding a-arylated aldehydes (10.15, R=H) or ketones (10.15, R=alkyl). Obviously the C=N group of these oximes reacts like a C = C group in classical Meerwein reactions. It is interesting that the addition of some sodium sulfite is necessary for the Beech reaction (0.1 to 0.2 equivalent of CuS04 and 0.03 equivalent of Na2S03). 

Butenolides from aryl aldehydes and 7-keto acids, 43, 5... 

Alkanale und Aryl-aldehyde lassen sich ebenfalls mit aquimolaren Mengen Triathyl-si-liciumhydrid (Trifluoressigsaure, 20°) in symm. Ather iiberfiihren z.B.2 ... 

Dihydropyrans [71] and 4-dihydropyranones [72] have been prepared by BF3 or Me2AlCl catalyzed Diels-Alder reactions of alkyl and aryl aldehydes with dienes 72 and 73 (Equations 3.20 and 3.21). Allylic bis-silanes are useful building blocks for synthesizing molecules of biological interest [73], 4-Pyra-nones have been obtained by cerium ammonium nitrate (CAN) oxidation of the cycloadducts. 

Cycloaddition reactions of the simple alkyl and aryl aldehydes 65 with (E)-l-methoxy-1,3-butadiene (18b) under high pressure conditions afforded adducts 66 and 67 in reasonable to good yields [2g, 23]. A marked preference for the c applying pressure enforces cnJo-addition (Scheme 5.5). Using mild Lewis-acid catalysts [24], such as Eu(fod)3, Yb(fod)3, or Eu(hfc)3, in combination with pressure, allows good results to be obtained with the added advantage of reducing the pressure to 10 kbar [25] (Scheme 5.5). 

Ketonitriles Preparfx) by Cyanide-Catalyzed CoNJuoArii Addition of Aryl Aldehydes to a,0-UNSATURATED Nitriles... 

CHROMIUM TRIOXIDE-PYRIDINE COMPLEX, preparation in situ, 55, 84 Chrysene, 58,15, 16 fzans-Cinnamaldehyde, 57, 85 Cinnamaldehyde dimethylacetal, 57, 84 Cinnamyl alcohol, 56,105 58, 9 2-Cinnamylthio-2-thiazoline, 56, 82 Citric acid, 58,43 Citronellal, 58, 107, 112 Cleavage of methyl ethers with iodotri-methylsilane, 59, 35 Cobalt(II) acetylacetonate, 57, 13 Conjugate addition of aryl aldehydes, 59, 53 Copper (I) bromide, 58, 52, 54, 56 59,123 COPPER CATALYZED ARYLATION OF /3-DlCARBONYL COMPOUNDS, 58, 52 Copper (I) chloride, 57, 34 Copper (II) chloride, 56, 10 Copper(I) iodide, 55, 105, 123, 124 Copper(I) oxide, 59, 206 Copper(ll) oxide, 56, 10 Copper salts of carboxylic acids, 59, 127 Copper(l) thiophenoxide, 55, 123 59, 210 Copper(l) trifluoromethanesulfonate, 59, 202... 

CYANIDE-CATALYZED CONJUGATE ADDITION OF ARYL ALDEHYDES 4-(3-PYRIDYL)-4-OXOBUTYRONITRILE... 

Li T, JPN Rosazza (1997) Purification, characterization, and properties of an aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646. J Bacteriol 179 3482-3487. 

Li T, JPN Rosazza (1998) NMR identification of an acyl-adeylate intermediate in the aryl-aldehyde oxidoreductase catalyzsed reaction. J Biol Chem 273 34230-34233. 

Gross GG (1972) Eormation and reduction of intermediate acyladenylate by aryl-aldehyde. NADP oxidor-eductase from Neurospora crassa. Eur J Biochem 31 585-592. 

Related oxidation processes have been reported that allow the generation of esters directly from aryl aldehydes [6] and the hydroacylation of a-keto esters with aldehydes [7]. 

Organozinc reagents have been used in conjunction with a-bromovinylboranes in a tandem route to Z-trisubstituted allylic alcohols. After preparation of the vinylborane, reaction with diethylzinc effects migration of a boron substituent with inversion of configuration and exchange of zinc for boron.176 Addition of an aldehyde then gives the allylic alcohol. The reaction is applicable to formaldehyde alkyl and aryl aldehydes and to methyl, primary, and secondary boranes. 

Alkenylsilanes can be prepared from aldehydes and ketones using lithio(chloromethyl)trimethylsilane. The adducts are subjected to a reductive elimination by lithium naphthalenide. This procedure is stereoselective for the E-isomer with both alkyl and aryl aldehydes.82... 

The stereoselectivity in this case is attributed to elimination through a cyclic TS, but is considerably reduced with aryl aldehydes. 

Scheidt reports using an amended Rokita method in conjunction with an umpolung derivative of several aryl aldehydes for the synthesis of a-aryl ketones.7 The procedure is indeed useful for the synthesis of 2-arylated benzofurans as shown by the synthesis of demethylmoracin I (Fig. 4.8). 

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

Scheme 1.22 Kitamura and Noyori s mechanism of the asymmetric addition of dialkyl zinc to aryl aldehydes.

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