Aryl ketones selectivity

The Nazarov cyclization of vinyl aryl ketones involves a disruption of the aromaticity, and therefore, the activation barrier is significantly higher than that of the divinyl ketones. Not surprisingly, the Lewis acid-catalyzed protocols [30] resulted only in decomposition to the enone derived from 46,47, and CO. Pleasingly, however, photolysis [31] readily delivered the desired annulation product 48 in 60 % yield. The photo-Nazarov cyclization reaction of aryl vinyl ketones was first reported by Smith and Agosta. Subsequent mechanistic studies by Leitich and Schaffner revealed the reaction mechanism to be a thermal electrocyclization induced by photolytic enone isomerization. The mildness of these reaction conditions and the selective activation of the enone functional group were key to the success of this reaction. 

This observation has led to the preparation of more effective bicyclic oxaza-borolidines such as 1, prepared from (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine and BH3 (la) or methylboronic acid (lb). Both reagents catalyze borane reduction of alkyl aryl ketones to furnish (R)-alcohols in > 95% ee, by face-selective hydride transfer within a complex such as B. Catalyst lb is somewhat more effective than... 

The retention indices, measured on the alkyl aryl ketone scale, of a set of column test compounds (toluene, nitrobenzene, p-cresol, 2-phenyl ethanol, and IV-methylaniline) were used to determine the changes in selectivity of a series of ternary eluents prepared from methanol/0.02M phosphate buffer pH 7 (60 40), acetonitrile/0.02 M phosphate buffer pH 7 (50 50) and tetrahydrofuran/0.02 M phosphate buffer pH 7 (25 65). The analyses were carried out on a Spherisorb ODS reversed-phase column. The selectivity changes were often nonlinear between the binary composition [83]. 

In situ production of phosphine-free CuH from CuCl or CuOAc (0.3-1.0 equivalents), in the presence of an excess of PhMe2SiH in DM I at room temperature, displays a remarkable preference for reductions of aryl ketones (e.g., 15) over aliphatic ones such as 16 (Eq. 5.23) [46]. Reactions require a day or more to reach completion, concentrations of 0.5 M notwithstanding, but yields have been uniformly good (77-88%) for the few cases examined. Aldehydes, however, show no such selectivity and are reduced to the corresponding primary alcohols, albeit in high yields. 

Insertion of aUcynes into aromatic C-H bonds has been achieved by iridium complexes. Shibata and coworkers found that the cationic complex [Ir(COD)2]BF4 catalyzes the hydroarylation of internal alkynes with aryl ketones in the presence of BINAP (24) [111]. The reaction selectively produces ort/to-substituted alkenated-aryl products. Styrene and norbomene were also found to undergo hydroarylation under similar condition. [Cp IrCl2]2 catalyzes aromatization of benzoic acid with two equivalents of internal alkyne to form naphthalene derivatives via decarboxylation in the presence of Ag2C03 as an oxidant (25) [112]. 

In addition, unstabilized enolate nucleophiles have been generated by decarboxylation of (3-ketocarboxylates. In this case, no additives are required to activate the nucleophile, but the highest yields and selectivities were obtained in the presence of two equivalents of DBU [82]. Although reactions of allylic carbonates containing aromatic, heteroaromatic, and aliphatic substituents occurred, only reactions to form aryl ketone products were published. 

Another class of ligands for ATH is represented by multidentate Schiff bases and their derivatives. Zassinovich and Mestroni reported on the effective reduction of alkyl aryl ketones catalyzed by a series of lr(l) complexes with chiral bidentate pyridylaldimines, of the form [lr(cod)(NNR )]C104 (76a-f see Scheme 4.31). It was observed that both the activity and selectivity depended heavily on the nature of the subshtuents at the chiral center of the ligand, and also at the prochiral center of the substrate. Optical yields of up to 50% (R-isomer) at 100% conversion were obtained in the ATH of BuC(0)Ph and PhCH2C(0)Ph using [lr(cod)(PPEl)]C104 as the precatalyst (0.1% mol, 83 °C, PrOH, KOH) [66]. 

A further example of the use of a chiral anion in conjunction with a chiral amine was recently reported by Melchiorre and co-workers who described the asymmetric alkylation of indoles with a,P-unsaturated ketones (Scheme 65) [212]. The quinine derived amine salt of phenyl glycine (159) (10-20 mol%) provided the best platform with which to perform these reactions. Addition of a series of indole derivatives to a range of a,P-unsaturated ketones provided access to the adducts with excellent efficiency (56-99% yield 70-96% ee). The substrates adopted within these reactions is particularly noteworthy. For example, use of aryl ketones (R = Ph), significantly widens the scope of substrates accessible to iminium ion activation. Expansion of the scope of nucleophiles to thiols [213] and oximes [214] with similar high levels of selectivity suggests further discoveries will be made. 

A similar study of Norrish II reactions has been conducted on complexes of aryl ketones in Dianin s compound 1 [295], a nonpolar host whose channels are effectively truncated at each 11A of length by a 2.8-A constriction from 6 hydrogen-bonding hydroxyl groups (see Figure 3) [296]. Table 13 summarizes the results from complexes with ketones expected to undergo primarily the Norrish II reactions [297]. As befits the rather large (and mostly) nonpolar reaction cavities, the E/C and t/c ratios in Table 13 provide evidence for relatively little control by the channels of Dianin s compound over the fate BRs. Even in the most selective case from 5-methyl-... 

Aryl ketones can also be prepared by C-acylation of support-bound arylstannanes with acyl halides (Entry 4, Table 12.1). The reaction conditions are mild and suitable for selective chemical transformations of polystyrene-bound intermediates. As an alternative, resin-bound arylstannanes can be converted into benzophenones by treatment with aryl halides and carbon monoxide ([(Pd(PPh3)4], DMSO, 80 °C, 18 h-3 d [8]). 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Aryllead triacetates a-arylate ketones highly selectively, working well for tertiary a-carbons, or secondary ones activated by a phenyl group,146 thus favouring arylation of positions that are typically already crowded, making the reaction very useful synthetically. 

Divalent tin enolates of ketones also react with another ketone to form cross-aldols in good to excellent yield. Enhanced /Areo-selectivity is observed in the case of aryl ketones.4 Example ... 

Some tricyclic 1,3-thiazetidines of type (51) are reported (95CPB63). Selective C-S bond cleavage of 3-aryl-fS-sultams (52) with ethylaluminium dichloride gives aryl ketones or aldehydes by a process involving 1,2-aryl shift, imine formation and hydrolysis of the imine (95TL245). 

Selective C-S bond cleavage of a /3-sultam ring bearing a variety of substituents at C-3 and C-4 can be achieved by reaction with Lewis acids and yields aryl ketones or aldehydes. A solution of ethylaluminium dichloride in hexane is easier to handle than solid aluminium chloride due to their relative moisture sensitivities (Scheme 25) <1998T8941>. 

Although allyl-arenes are prone to olefin isomerization, several successful reactions have been performed, for example in the chemoselective oxygenation of 22 to aryl-acetone 23 (Table 2) [38]. Allyl alcohols sometimes react sluggishly, but examples with high ketone selectivity are known, for example the oxidation of tertiary alcohol 24 to a-hydroxyketone 25 [39]. 

The cooperative complex of ALB 2 and La(OTf)3.nH20 catalyze direct asymmetric Mannich-type reactions with good selectivity providing /3-amino aryl ketones in good yields and with 31-44 % ee. 

Benzylmanganesepentacarbonyl, BzlMn(CO)s (1) indenols,1 Aryl ketones react with 1 selectively at the orr/io-position to form a manganacycle (2), which after oxidative decarbonylation with (CH3)3NO in CH3CN is converted into a product (a) that reacts regioselectively with alkynes to form substituted l-alkyl-l//-inden-7-ols (3). This reaction is regioselective a terminal alkyne reacts to form 2-sub-... 

Pioneering work on the photochemical diastereocontrol in zeolite supercages was reported by Turro and coworkers in 1991 [48]. They investigated the diastereoselective photodecarbonylation of 2,4-diphenyl-3-pentanone (DPP) adsorbed in various cation-exchanged X and Y zeolites to find that the diastereo-selectivity of d9l- over mestf-2,3-diphenylbutane increases in the order LiX NaX < LiY NaY < KY. In 1996, Ramamurthy and coworkers reported the first example of photochemical asymmetric induction in chirally modified zeolites [49], where they employed the Norrish/Yang type II reaction of cis-4-tert-butyl-cyclohexyl aryl ketones to the corresponding cyclobutanols. Since then, a variety of asymmetric photoreactions in zeolite supercages have been reported as reviewed below. 

For aryl ketones the Corey-Bakshi-Shibata (CBS) reduction using oxazaborolidines as catalysts for the boron hydride mediated hydrogenation is particularly useful, with maximum selectivities up to 99 % ee (see Scheme 4) [34]. The excellent review by Corey et al. [35] also shows clearly the power for chemo- and enantioselective reduction of purely aliphatic a,//-enones and -ynones only on the carbonyl group. In the re-... 

Only one equivalent of base is required for the trifluoroacetylation step apparently the chelated tetrahedral intermediate is stable at -78°C and the ft-dicarbonyl product is not generated until workup. Crucial to the success of the trifluoroacetylation reaction in some cases is the selection of lithium hexamethyldisilazide (LiHMDS) for the generation of the ketone enolate under otherwise identical conditions diazo transfer to several aryl ketones proceeds in dramatically reduced yield when lithium diisopropylamide is employed as base. 

In an industrial asymmetric synthesis en route to the antiinflammatory agent naproxen, the dimethyl L-tartrate acetals of ethyl aryl ketones are brominated in high yield and selectivity to give the corresponding a-bromo derivatives. Subsequent stereospecific Ag -promoted 1,2-aryl migration provides the 2-alkyl-2-arylacetic acid after hydrolysis of the tartrate auxiliary, which is recovered (e.g. eq 4). 

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