Aryl derivatives ketones

Superacids such as HF-SbF effect cyclo alkylation of aryl alkyl ketones to give tetralone derivatives (58). Tandem iatramolecular cyclo alkylatioas can be achieved when functional groups are located ia close proximity (59). 

Aldehydes and ketones of furazans and furoxans have many properties resembling those of the aryl derivatives. Reduction of the carbonyl compounds with... 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

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. 

Reactions of organometallic derivatives with ketones, which are less electrophilic than aldehydes, usually require an equimolar amount of a chiral ligand. The first catalytic enantioselective addition of an organometallic reagent, namely ZnPh2, to dialkyl and aryl alkyl ketones was reported in 1998 by Dosa and Fu (Scheme 110).288 The procedure... 

The combination of [Rh(Cl(NBD)]2 and ligands 89, 90, 91, or 92 with diphenylsilane asymmetrically reduces aryl alkyl ketones, including acetophenones, in excellent yields and in 81 to 90% ee (Eq. 346).574 The best results are with ferrocene 91 and acetophenone in toluene.575 Other phosphine-substituted ferrocenes do not give comparable results. Rhodium(I) complexes of TADDOL-derived... 

Sinou and coworkers evaluated a range of enantiopure amino alcohols derived from tartaric acid for the ATH reduction of prochiral ketones. Various (2R,iR)-i-amino- and (alkylamino)-l,4-bis(benzyloxy)butan-2-ol were obtained from readily available (-I-)-diethyl tartrate. These enantiopure amino alcohols have been used with Ru(p-cymene)Cl2 or Ir(l) precursors as ligands in the hydrogen transfer reduction of various aryl alkyl ketones ee-values of up to 80% have been obtained using the ruthenium complex [93]. Using (2R,3R)-3-amino-l,4-bis(benzyloxy)butan-2-ol and (2R,3R)-3-(benzylamino)-l,4-bis(benzyloxy)butan-2-ol with [lr(cod)Cl]2 as precursor, the ATH of acetophenone resulted in a maximum yield of 72%, 30% ee, 3h, 25 °C in PrOH/KOH with the former, and 88% yield, 28% ee, 120 h with the latter. 

Fluorosilylsubstituted aryl derivatives were found to be useful reagents for carbon-carbon bond formation via palladium-catalyzed cross-coupling with aryl halides in the presence of fluoride anions as Si—C bond activator in dimethylformamide (DMF), as well as rhodium-catalyzed 1,4-addition to a, 3-unsaturated ketones in the presence of a fluoride anion source (Equation 14.11) [66, 69, 70],... 

Furthermore, Rueping and coworkers applied their reaction conditions to the cyanation of ketimines [54]. The use of A-benzylated imines derived from aryl-methyl ketones generally gave comparable yields, but lower enantioselectivities. However, this method furnished Strecker products bearing a quaternary stereogenic center, which are valuable intermediates for the preparation of optically active a,a-disubstituted a-amino acids. 

BINOL phosphate (5)-3o (10 mol%, R = 2,4,6- PTj-C Hj) turned out to be the catalyst of choice and gave iV-acetylated 3-indolyl amines 128 bearing a qnatemary stere-ogenic center in excellent yields (94-99%) with high enantioselectivities (73-97% ee). Enamides derived from aryl-methyl ketones as well as indoles with varions substitnents conld be employed. 

Scheme 6.94 Typical products obtained from the 86-catalyzed Michael addition of aryl methyl-ketone-derived morpholine enamines to various aromatic nitroalkenes and subsequent acidic hydrolysis.

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

The regiochemistry of arylation of ketones has not been studied systematically, but there are sufficient data in the literature to allow reasonable predictions to be made. With enolates having one r-alkyl group attached to the carbonyl (e.g. "Cl COBu ) or with those derived from aryl alkyl ketones, clearly no prob-... 

Shibasaki has examined catalysis of a complex, prepared in situ from PdCl2, AgOTf, (R)-or (S)-BINAP, 4 A molecular sieves, and H20, in the aldol addition reaction of enolsilanes by (Eq. 8B2.5) [13]. Under these conditions, aryl methyl ketone-derived trimethylsilyl enolates add to benzaldehyde and hydrocinnamaldehyde, affording adducts with up to 73% ee. 

Grignard reagents derived from aryl bromides are readily prepared and may be converted into organocadmium compounds by treatment with cadmium chloride (cf. Section 5.8.4, p. 616). Reaction of an organocadmium with a carboxylic acid chloride constitutes a convenient synthesis of aryl alkyl ketones. 

Participation of proton-donors other than hydroxonium ion has been observed, e.g. for phenylglyoxylic (59) and pyruvic (60) acids, for substituted benzaldehydes (61—63), unsaturated acids (49, 64), N-nitros-amines (65), nitrones (66), unsaturated ketones (67), aryl alkyl ketones (68) and various heterocyclic compounds (69, 70). Consecutive dissociation has been observed for maleic and fumaric acids (48), for phthalic acid (50) and for pyridoxal derivatives (71). 

As noted already, the reactions of oc,(3-unsaturated ketones with or /zo-diamines are often accompanied by various rearrangements and side processes. For instance, the o-PDA condensation with chalcone in the presence of an acid catalyst or during overheating of the reaction mixture produces a final product of 2-phenylbenzimidazole [2, 7] a similar phenomenon is also observed for 2,3-diaminopyridine [54]. Owing to the existence of much more suitable approaches to the synthesis of 2-aryl derivatives of benzimidazole and their heteroannelated analogues (e.g., proceeding from diamines and acids or aldehydes [121]), such a trend in the interaction of chalcones with diamines is unlikely to have any application for this purpose. 

BH3.Me2S reduction of aryl alkyl ketones can be carried out with ees up to 98% using 3 mol% of a chiral oxazaborolidine derived from (-)-/l-pinenc.3 5... 

An easy and simple synthesis of different chiral fran -l-arenesulfonylamino-2-isoborneolsulfonylaminocyclohexane derivatives (41) has been reported.108 These ligands have proved to be excellent promoters for the catalytic enantioselective alkylation and arylation of ketones (up to 99% ee), very good for the alkenylation process, and modest for the allylation and alkynylation reactions. 

The other way to prepare cyclopropanes is based on the spin-center-shift. Thus, aryl-alkyl ketones, 26, bearing a leaving group X adjacent to the excited carbonyl group undergo a smooth cyclization to benzoylcyclopropanes 27 in moderate to good yields (Scheme 6b) [4a, b]. The reaction tolerates a variety of functional groups, often proceeds stereoselectively, and can be extended to the preparation of bicyclo[n.l.O]alkane derivatives. 

The ketones derived from thiopyrans are 2//-thiopyran-2-one 25 and 47/-thiopyran-4-one 26 and the benzologues are 2//-1 -benzothiopyran-2-one or thiocoumarin 27, 4//-l-benzothiopyran-4-one (thiochromone) 28, and 9//-thiox-anthen-9-one or simply thioxanth-9-one 29. The trivial names dihydrothiocoumarin and thiochroman-4-one are used for the partially reduced derivatives. l//-2-Benzothiopyran-l-one 30 is usually known as isothiocoumarin. The 2- and 3- aryl derivatives of 10, 28, and 31 are generally referred to as the thioflavonoids. 

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