SUBSTITUTED ALDEHYDES AND KETONES

Several approaches to a-hydroxy ketones which involve carbon-carbon bond formation have been reported. These include the reaction of Grignard reagents with the - trimethylsilyl ethers of 

A procedure for the preparation of o-fluoroketones and fluoroaldehydes by the low temperature fluorination of silylenol ethers with 5% fluorine gas in nitrogen with freon 11 as solvent has been published. The yields were generally good, although some 

Protected a-bromoalkyl aryl ketones may be prepared by the asymmetric bromination of enantiomerically pure acetals. Both yields and optical purities were high, and little racemisation was 

N-Dialkylaminomethyl ketones may be prepared in good yields by the reaction of (N, N-dialkylaminomethyl) tributyltin reagents with acid 

A procedure for the preparation of cyclic chiral a-sulphinyl ketones by the boron trifluoride etherate catalysed reaction of methyl toluenesulphinate with silyl enol ethers has been described [equation (32) 

Enones can be converted into their 2-halo derivatives by reaction of their a-seleno derivatives (generated in situ) with further selenating agent [equation (40)]. Complexes of a-acetylenic alcohols and iodine are oxidized by pyridinium dichromate to a-iodo-enones [equation (41)].  

Phosphorus tri-iodide and diphosphorus tetraiodide cleanly reduce a-bromo-and a -iodo-ketones to ketones.a -lodo-ketones are deiodinated by thiols and 

Antonioletti, M. D Auria, G. Piancatelli, and A. Scettri, Tetrahedron Lett., 1981, 22,1041. 

Various methods for the a-hydroxylation of carbonyl compounds have appeared. lodosobenzene shows a high degree of selectivity in the preparation of acyloins, and benzeneseleninic anhydride appears to be an excellent reagent for the hydroxylation at the tertiary centre in a-alkylcycloalkanones. Enol silyl ethers give acyloins with osmium tetroxide and V-methylmorpholine V-oxide,and a-acyloxycarbonyl compounds with silver acetate and iodine. a-Acyloxyketones may also be prepared conveniently by treatment of oximes with acid chlorides [equation (42)].  

Reagents i, Bu Li ii, EtCHO iii, NH4CI iv, DMS0-(CF3C0)20 v, Et3N vi, PrMgBr vii, NCS-AgNOs 

a -dihydroxyketone functionality, which occurs in a number of molecules of biological interest, can be prepared by oxidative hydration of propargylic alcohol precursors with 

Japanese workers have found that in the presence of small amounts of triethylamine in warm ethanol the thiazolium salt (27) efficiently catalyses the cross benzoin reaction of 

The acylation of a-alkoxylithium reagents, prepared by the transmetallation of the corresponding stannanes,with a tertiary amide, provides an interesting and flexible approach to acyloin products. Intramolecular condensations are also possible allowing the preparation of small and normal ring ketones [equation (31)].  

Chlorination of ketones, along with a number of other functional groups, may be achieved with trichloroisocyanuric acid and per-a-chlorinated ketones may be prepared by reaction of manganese(III) acetate with ketones in the presence of lithium chloride.  

Reagents, i. PhSeX ii. H Oy pyridine iii, MeOH.NaHCO iv, LiCOj, DMF 

Reagents i, cathode, CCU.CHClj ii, NaH iii, Mel iv, cathode, MeOH-H20 v, CrOj vi, KOBu vii, H2S04,H20 viii, KOH,ElOH 

Sodium dithionite in water or aqueous dimethylformamide is an economic, efficient system for the dehalogenation of a-halo-ketones. Other reagents that have been described recently for dehalogenation include iron-graphite (prepared by reduction of ferric chloride with potassium-graphite), sodium 0,0-diethyl phosphorotelluroate, and sodium borohydride in the presence of a catalytic amount of bis(2-thienyl) ditelluride.  

A hydroxyl group may be introduced a- to a ketone group by the reaction of chromyl chloride with the ketone silyl enol ether in dichloromethane at low temperature, No a-chloro-ketones were observed as by-products. Alternatively, an alkoxy-group may be introduced by the reaction of the silyl enol ether with alkyl hypochlorites, catalysed by tetrakis(triphenylphosphine)palladium.  

Yamazaki, and H. Ohmizu, Tetrahedron Lett., 1982,23, 1609. 

Reagents i, Na0C0Ph,PhH.H 0,Bu3NBr ii, MeCOCH2CO Et,TiCl4, pyridine iii. (Ph,P)4Pd 

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Based on this variety of properties, amorphous polybutadiene has found a niche in the mbber industry. Moreover, it appears that the anionicaHy prepared polymer is the only polymer that can be functionalized by polar groups. The functionalization is done by using aromatic substituted aldehydes and ketones or esters. Functionalization has been reported to dramatically improve polymer-filler interaction and reduce tread hysteresis (70—73). 

The Stork enamine reaction is an important and versatile method for the synthesis of a-substituted aldehydes and ketones. Such products should in principle also be... 

The nucleophilic alkenoylation of a-phenyl-substituted aldehydes and ketones with (methyl-substituted) [l-cyano-l-(trimethylsilyloxy)-2-propenyl]lithium proceeds with good 1,2-induction to afford the j> i-hydroxy ketones109. 

Excellent simple (90-100%) and induced diastereoselectivities (92-100%) were observed in the syntheses of 3,4-disubstituted 5-oxoalkanoates using, instead, various substituted aldehydes and ketones to prepare the chiral hydrazones. 

Some chiral 1,3,2-dioxastannolanes were used as catalysts in asymmetric Diels-Alder reactions of cyclopentadiene with methyl acrylate <90JCR(S)278>. A-Alkenyl- and -cycloalkenyl 1,3,2-oxaza-stannolanes, generated in situ from chiral amino alcohols, gave optically active 2-substituted aldehydes and ketones in modest to high chemical and optical yields after alkylation with methyl acrylate or acrylonitrile (which is usual for enamines) and subsequent hydrolysis <85CC504,85JOC3863>. 

The acyclic aldehydes and ketones are expected to give substantially weaker CD than that of their cyclic counterparts because of the conformational mobility of the former, as was borne out by Djerassi and Geller75 in an early study of a series of optically active methyl-substituted aldehydes and ketones. Since then only a few studies on acyclic aldehydes and ketones have appeared76,77. 

In all of the reactions with carboxylic acid derivatives, the carbonyl carbon is acting as the substrate in nucleophilic substitution. Rather than memorize all these reactions, you should remember that carboxylic acids and their derivatives undergo nucleophilic substitution aldehydes and ketones prefer nucleophilic addition. 

Both chiral amines42 and chiral protonating agents43 have been used for the enantioselective deracemisation of a-substituted aldehydes and ketones via the derived enamine. However, the enantiomeric excesses achieved were usually not very high and there have been no new developments reported in this area41. 

Cycloalkylation of substituted aldehydes and ketones with the formation of heterocycles 87CRV1277. 

The reaction is most useful for the preparation of olefinic, halo, and nitro alcohols from the corresponding substituted aldehydes and ketones. These substituents ate very often affected by other reduction procedures. Excellent directions are found in the preparations of crotyl alcohol (60%), l-bromo-5-hexanol (64%), l-chloco-4-pentanol (76%), /S,/S,/S-trichloroethyl alcohol (84%), methyl-p-chlorophenylcarbinol (81%), and o-nitrobenzyl alcohol (90%). The reaction has also been used in the preparation of certain tetralols and decalols as well as 9-fluo-renylcarbinol (50%). The thiophene and furan nuclei are not reduced. 

Quadridentate ligands can be obtained by condensing suitably substituted aldehydes and ketones with bidentate primary amines, and the resulting Schiff bases closely resemble the porphin ring system. Generally, one of the structural units—N=C—C=N—,—N=C—NHC=N—, N=C—NH—N=C—, —C=N—CH=CH—N=C—, or —C=N— CH2—CH2—N=C—is incorporated into the structure for maximum stability. For example, if or /io-aminobenzaldehyde is condensed with ortho-... 

C. SUBSTITUTED ALDEHYDES AND KETONES I. HALOGEN ALDEHYDES Tri-chlor Aldehyde CCI3—CHO Chloral... 

SUBSTITUTED ALDEHYDES AND KETONES HYDROXY ALDEHYDES AND HYDROXY KETONES... 

The alkylation of a-hetero substituted aldehydes and ketones is often a far from simple process. However methods for both the a and a -alkylation of fluoroacetone by way of its lithium N-cyclohexyl enamide,1 0 and the alkylation of formamido ketones1 1 have been reported. The allylation of ketones has received a... 

For synthetic purposes, the electrophilic reagents that give the best yields of a-substituted aldehydes and ketones on reactions with enamines are the following ... 

Larock, R.C., Leung, W.Y. and Stolz-Dunn, S. (1989) Synthesis of aryl-substituted aldehydes and ketones via palladium-catalyzed coupling of aryl halides and non-allyUc unsaturated alcohols. Tetrahedron Lett., 30, 6629-32. 

An 5 n2 allylic substitution of l,3-diphenyl-2-propenyl acetate by the enamine nucleophile produced from ketones and aldehydes gives C -substituted aldehydes and ketones in moderate to high yields (60-95%) and high enantioselectivities (79-98% ee). The reaction requires the presence of a palladium catalyst, pyrrolidine, and water. The palladium catalyst was prepared from a chiral ferrocene P,N ligand when a ketone was used, but with a ruthenium-based P,P ligand when an aldehyde was used in the reaction. 

Aldehydes and ketones are useM building blocks in organic synthesis. The direct a-C-H substitutions of carbonyl compounds are well known. However, selective P-C(sp )-H functionalization remains rare. The MacMillan group introduced Site activation model by dual aminocatalysis and photocatalysis, opening up a practical synthetic route to P-substituted aldehydes and ketones (Scheme 3.25). With this novel strategy, radical-radical coupling of enaminyl radical with electron-poor cyanobenzene radical anion can elegantly produce P-aiylated aldehydes and ketones [74]. A recombination of enaminyl radical with imine anion radical was also developed [75]. In the presence of Michael acceptors, radical addition of enaminyl radical to electron-deficient alkenes affords P-alkylated aldehydes [76]. 

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