Aryl aldehydes selectivity

On the other hand, the oxidation of the alkyl substituent in alkyl aromatic compounds can be carried out by various methods efficiently. For example, CAN has been used to oxidize substituted toluene to aryl aldehydes. Selective oxidation at one methyl group can be achieved (Eq. 7.19).44 The reaction is usually carried out in aqueous acetic acid. 

Multicomponent reactions, which have been known for over 150 years, are those chemical transformations in which more than two reactants combine in a sequential manner to give highly selective products that retain majority of the atoms of the starting materials [36]. Because of the inherent molecular diversity, efficiency, and atom economy, they are highly sought after by chemists and have been widely used in the synthesis of some heterocyclic compounds. Hu and coworkers reported one unique example wherein the electron-rich aryl aldehydes selectively formed a carbonyl ylide with phenyldiazoacetate, which successively cyclized with electron-deficient aryl aldehydes to give the dioxolane (Scheme 2.22) [37]. 

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. 

Grigg et al. (34) also conducted extensive studies of the thermal 1,2-prototropic generation of azomethine ylides and this can be exemplihed by the diastereofacially selective cycloaddition of 7-aminocephalosprin ylide precursors. Condensation of aryl aldehydes with 120, in refluxing toluene, furnished imines 121, which, in the presence of A -phenylmaleimide, furnished a mixture of cycloadducts 122 and 123 in essentially quantitative yield in a 2 1 ratio. The only observed products... 

The carbonyl ylide generated from metal carbene can also add to C=0 or C=N bonds. The [2 + 3]-cycloaddition of carbonyl ylide with G=0 bond has been used by Hodgson and co-workers in their study toward the synthesis of zaragozic acid as shown in Scheme n 27a,27d Recently, a three-component reaction approach to syn-a-hydroxy-f3-amino ester based on the trapping of the carbonyl ylide by imine has been reported.The reaction of carbonyl ylide with aldehyde or ketone generally gives l,3-dioxolanes. Hu and co-workers have reported a remarkable chemoselective Rh2(OAc)4-catalyzed reaction of phenyl diazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes. The Rh(ii) carbene intermediate reacts selectively with electron-rich aldehyde 95 to give a carbonyl ylide, which was chemospecifically trapped by the electron-deficient aldehyde 96 to afford 1,3-dioxolane in a one-pot reaction (Equation (12)). 

Fu has also achieved the addition of 2-cyanopyrrole to arylalkylketenes, again using PPY 4c (2 mol%) as catalyst in toluene at rt, and with similarly high selectivity and yield [59]. Additionally, related processes have been developed for the asymmetric preparation of /Mactams [67] and /Mactones [63] by the formal [2+2]-cycloaddition of N-tosylaldimines and aryl aldehydes, respectively, to Ice-... 

Selective reduction of aldehydes. In the absence of radical initiators, tributyltin hydride does not ordinarily reduce carbonyl groups. However, when slurried in cyclohexane with dried silica gel (activated by heating at 220° under reduced pressure), this hydride reduces aldehydes and ketones to alcohols in high yield. The rate of reduction is aldehydes > dialkyl ketones > aryl alkyl ketones > diaryl ketones. Thus it is possible to reduce aldehydes selectively. The function of Si02 apparently is that of a mild acid catalyst. 

Hydroxyketones are versatile intermediates in the synthesis of pharmaceutical intermediates and heterocyclic molecules. a-Aryl hydroxyketones have been prepared by reaction of aryl aldehydes with 1,4-dioxane followed by reduction with lithium aluminum hydride (LAH) and by the selective LAH reduction of a-silyloxy a,P-unsaturated esters." WissneC has shown that treatment of acid chlorides with tris(trimethylsilyloxy)ethylene affords alkyl and aryl hydroxymethyl ketones. 1-Hydroxy-3-phenyl-2-propanone (3) has been generated by the osmium-catalyzed oxidation of phenylpropene and by the palladium-catalyzed rearrangement of phenyl epoxy alcohoP both in 62% yield. 

N-l-Protected 2,4,5-triiodoimidazole 243 was selectively lithiated at the 2-position via iodine-lithium exchange (Scheme 58) (2005S136>. The lithiated species was then quenched by a number of aryl aldehydes 244 to give unsymmetrical diarylmethyl alcohols 245 in high yields. The high yields of these reactions indicated that the iodine-lithium exchange of this triiodoimidazole is efficient and selective. 

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 hydrogenation of aryl aldehydes and ketones is complicated by the potential for the hydrogenolysis of the resulting benzyl alcohol as well as benzene ring hydrogenation (Eqn. 18.3). With the proper selection of reaction conditions... 

Since aliphatic aldehydes and ketones are not hydrogenated over palladium, this reaction provides a means of selectively removing an aromatic carbonyl group in the presence of an aliphatic aldehyde or ketone (Eqn. 18.10).32 The palladium catalyzed hydrogenolysis of aryl aldehydes and ketones is preferable to any of the chemical reduction procedures such as the Wolff-Kishner or Clemmenson reactions for the removal of an aryl carbonyl group. 

S-Benzyl-y-butyrolactones (44) for which convenient preparative procedures are available, and improved techniques for their a-alkylation and a-hydroxyalkylation, provide the most common synthetic route for these lignan sub-classes (39). The Stobbe condensation (40) of aryl aldehyde with dimethyl succinate (Scheme 9) leads to the half-ester (42) which can be catalytically hydrogenated at atmospheric pressure to give the dihydro half-ester (43). Selective reduction of the potassium salt of the latter can be effectively achieved by calcium borohydride (41)... 

In order to investigate the electronic effects of equatorial diphosphines, electron-withdrawing substituents on the aryl rings were synthesized and tested [239]. The introduction of an electron-withdrawing group in the BISBI ligand increased the linear aldehyde selectivity in the hydroformylation of 1-hexene up to an l b ratio of 123 1. 

The results of irradiation ( i > 290 nm) of a series of aldehydes and ketones (91) in the presence of the silyl acetals (92) have been reported. The reactions are both solvent and silyl group dependent and the best results are obtained when the solvents used are /z-hexane, THF, diethyl ether or benzene and with the silyl group TBDMS. The products are the oxetanes (93) and the silyl-migrated product (94) in a ratio greater than 95 5 respectively. There is no evidence for the formation of the isomeric oxetane. Other studies from this research group" have examined the photochemical addition of a series of aryl aldehydes (95) to the cyclic silyl alkenes (96) brought about by irradiation at X,>290 nm in methylene chloride solution. The additions encountered take place with regio and exo selectivity as shown by the yields and ratios of the products (97). 

Finally, carbenoid species can be used as the carbon donor in aldehyde epoxidations. Thus, the rhodium carbenoid derived from the cyclic diazoamide 49 and rhodium(II) acetate reacts stereo selectively with aryl aldehydes to provide spiro-indolooxiranes 50 with Z-stereochemistry. The reaction is believed to proceed via the formation of a carbonyl ylide 51, which undergoes stereospecific thermal conrotatory electrocyclization to form the observed epoxide <04SL639>. 

The thiazolium-mediated three-component reaction of thiazolium salts 201, aryl aldehydes and dimethyl acetylenedicarboxylate provides a facile synthesis of 2-amino-2-arylfurans 202 <05OL1343>. The reaction pathway may involve the sequential nucleophilic addition of thiazol-2-ylidene 203 with the aldehyde and DMAD to form the spirocyclic intermediate 204 through the simultaneous formation of two C-C bonds and a C-O bond Selective ring opening of the spirocyclic intermediate 204 followed by hydrolysis leads to 3-aminofuran 202 via 205. 

Apart from sodium borohydride, which is frequently used in water or water-alcohol mixtures to reduce ketones or aldehydes selectively, water is rarely used as the solvent in reductions, because of incompatibility with most reducing agents. However, samarium iodide reduction of ketones, as well as alkyl and aryl iodides is accelerated in water [99]. Likewise, the a-deoxygenation of unprotected aldonolac-tones is efficient when the SmI2-tetrahydrofuran-water system is used [100],... 

Figure 16.4-1. Selected enzymatic oxidations of aldehydes. A oxidation of complex natural products such as retinal B oxidation of aliphatic and a,P-unsaturated aldehydes C oxidation of (hetero)arylic aldehydes D oxidative cleavage of the aldehyde-carbon atom yielding terminal alkenes.

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