Ketones, catalytic chiral

Recent advances in the asymmetric catalytic reduction of ketones using chiral oxazaborolidines as ligands 98MI64. 

Complexation of (124) and (125) with [ Rh(COD)Cl 2] in the presence of Si(OEt)4, followed by sol-gel hydrolysis condensation, afforded new catalytic chiral hybrid material. The catalytic activities and selectivities of these solid materials have been studied in the asymmetric hydro-gen-transfer reduction of prochiral ketones and compared to that of the homogeneous rhodium complexes containing the same ligands (124) and (125) 307... 

Early studies of the asymmetric reduction of prochiral ketones by chiral aluminum alkoxides have been reviewed by Morrison and Mosher (1). Doering and Young (123) reported the reduction of methyl cyclohexyl ketone with chiral 3-methyl-2-butanol in the presence of a catalytic amount of aluminum alkoxide to give the (S)-( + )-carbinol in a 22% optical yield. Jackman and co-workers (124) similarly reduced methyl n-hexyl ketone with chiral 3,3-dimethyl-2-butanol to the (S)-( - )-carbinol in a 6% optical yield. Other attempts resulted in similar low optical yields or gave only racemic products. Since the reductions were carried out under equilibrium conditions, racemization could have accounted for the low optical yields. 

Degni, S., Wilen, C.-E. and Rosling, A. Highly Catalytic Enantioselective Reduction of Aromatic Ketones using Chiral Polymer-supported Corey, Bakshi, and Shibata Catalysts. Tetrahedron Asymmetry 2004, 15, 1495-1499. 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (Eq. 6A.2) and may be generated by nucleophilic addition to an electrophile [25] or by addition of a formaldehyde equivalent to a preexisting terminal acetylene group [26], Once in place, reduction of the propargylic alcohol with lithium aluminum hydride or, preferably, with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) [27] will produce the trans allylic alcohol. Alternately, catalytic reduction over Lindlar catalyst can be used to obtain the cis allylic alcohol [28]. The addition of other lithium acetylides to ketones produces chiral secondary alcohols, which also can be reduced by the preceding methods to the cis or trans allylic alcohols. Additional synthetic approaches to allylic alcohols may be found in the various references cited in this chapter. 

Another more efficient catalytic version of the reaction consists of the interaction of ketones with chiral amines [6] to form enolate-like intermediates that are able to react with electrophilic imines. It has been postulated that this reaction takes place via the catalytic cycle depicted in Scheme 33. The chiral amine (130) attacks the sp-hybridized carbon atom of ketene (2) to yield intermediate (131). The Mannich-like reaction between (131) and the imine (2) yields the intermediate (132), whose intramolecular addition-elimination reaction yields the (5-lactam (1) and regenerates the catalyst (130). In spite of the practical interest in this reaction, little work on its mechanism has been reported [104, 105]. Thus, Lectka et al. have performed several MM and B3LYP/6-31G calculations on structures such as (131a-c) in order to ascertain the nature of the intermediates and the origins of the stereocontrol (Scheme 33). According to their results, conformations like those depicted in Scheme 33 for intermediates (131) account for the chiral induction observed in the final cycloadducts. 

A highly selective synthesis of homoallylic alcohols has been reported by Tietze et al.,917 who reacted methyl ketones, the chiral norpseudoephedrine derivative 285, and an allylsilane in the presence of a catalytic amount (0.2 mol%) of triflic acid [Eq. (5.340)]. The transformation was interpreted as an SN2 attack of the allylsilane to the protonated mixed acetal 286. The obtained ethers were then cleaved to the final product, homoallylic alcohols. 

Another fact is the quite impressive functional group selectivity of this method. Because of their greater reactivity imines can be reduced in the presence of ketones, although chiral Ru-complex 9 catalyzes the transfer hydrogenation of ketones. Besides this catalytic enantioselective reduction of imines others are known.8... 

The asymmetric sulfenylation of ketones with chiral sulfenamides is based on the direct reaction of 4-alkylcyclohexanones with optically active sulfenamides in the presence of a catalytic amount of triethylamine hydrochloride37. 

Other selected examples are summarized in Table 2. In addition to aldehydes, both cyclic and acyclic ketones can be reduced equally well. sec-Phenethyl alcohol (11, R = Ph) as hydride source works more effectively than t-PrOH. On the basis of this finding, the asymmetric MPV reduction of unsymmetrical ketones with chiral alcohol in the presence of catalyst 10 was examined [30]. Treatment of 2-chloroacetophenone (12) with optically pure (R)-(+)-sec-phenethyl alcohol (1 equiv.) under the influence of catalytic 10 at 0 °C for 10 h afforded (5)-(+)-2-chloro-l-phenylethanol (13) with moderate asymmetric induction (82 %, 54 % enantiomeric excess, ee Sch. 8). Switch-... 

The earliest report of a reaction mediated by a chiral three coordinate aluminum species describes an asymmetric Meerwein-Poimdorf-Verley reduction of ketones with chiral aluminum alkoxides which resulted in low induction in the alcohol products [1]. Subsequent developments in the area were sparse until over a decade later when chiral aluminum Lewis acids began to be explored in polymerization reactions, with the first report describing the polymerization of benzofuran with catalysts prepared from and ethylaluminum dichloride and a variety of chiral compounds including /5-phenylalanine [2]. Curiously, these reports did not precipitate further studies at the time because the next development in the field did not occur until nearly two decades later when Hashimoto, Komeshima and Koga reported that a catalyst derived from ethylaluminum dichloride and menthol catalyzed the asymmetric Diels-Alder reaction shown in Sch. 1 [3,4]. This is especially curious because the discovery that a Diels-Alder reaction could be accelerated by aluminum chloride was known at the time the polymerization work appeared [5], Perhaps it was because of this long delay, that the report of this asymmetric catalytic Diels-Alder reaction was to become the inspiration for the dramatic increase in activity in this field that we have witnessed in the twenty years since its appearance. It is the intent of this review to present the development of the field of asymmetric catalytic synthesis with chiral aluminum Lewis acids that includes those reports that have appeared in the literature up to the end of 1998. This review will not cover polymerization reactions or supported reactions. The latter will appear in a separate chapter in this handbook. 

Very recently it has been shown that electrode surfaces can be chemically modified.13 Although no useful reactions have come from this work, it has been shown that organic molecules can be covalently attached to electrode surfaces and that these modified surfaces impart selectivity to electrochemical reactions which is not otherwise available. Attempts have also been made to increase the selectivity of electrochemical reactions by adsorbing material on the electrode surface. In particular if chiral alkaloids are adsorbed on mercury, it Is then possible to perform the asymmetric reduction of prochiral ketones tc chiral alcohols. An optical yield of 54% has, for example, been reported for the reduction of 4-acetyl pyridine in aqueous-ethanol using strychnine as the catalytic, chiral reagent.11 ... 

The catalytic enantioselective reduction of 1-ketophosphonates has recently been developed. This approach takes advantage of a development in the enantioselective reduction of prochiral ketones to chiral alcohols by means of catalytic amounts of oxazaborolidines with borane as reducing agent. Thus, the enantioselective reduction of 1-ketophosphonates is accomplished by treatment with different boranes, BH. THF (0.9 eq), BII3Me2S (0.66 eq),5 545 qj- catccholborane (1.1 eq)5° 5 6 in different solvent systems in the presence of a catalytic amount of freshly prepared B-n-butyloxazaborolidine, (5) or (R) (Scheme 7.93). The reaction is complete in about 5 h and produces the expected dialkyl 1-hydroxyalkylphosphonates in satisfactory yields (53-98%). 

Rose Bengal xanthene dye photosensitizer, 277 Ruthenium, dihydrotetrakis(triphenylphosphine)- double bond shift in alkenes, 270 Ruthenium(2 +), chiral binap complexes asym. hydrogenation with, 102-103, 325-326 Ruthenium(8 +) oxide oxidation with of alcohols to ketones (catalytic), 267 of alkynes to 1,2-diones (catalytic), 117, 132 of ethers to esters, 118, 134-135... 

Corey EJ, Bakshi RK (1990) A New System for Catalytic Enantioselective Reduction of Achiral Ketones to Chiral Alcohols. Synthesis of Chiral a-Hydroxy Acids. Tetrahedron Lett 31 611... 

Subsequent Diels-Alder reaction with dienophile 35, generated in situ from Meldrum s acid 31 and the corresponding aldehyde, gave chiral spirocyclic compound 36 with excellent diastereo- and enantioselectivity (Scheme 6.7). Later, Cordova and co-workers [26], Melchiorre and co-workers [27], and Xu and coworkers [28] applied the same concept of catalytic chiral diene formation in the DA of a, 3-unsaturated ketones with different dienophiles (Scheme 6.8). 

Tian SK, Hong R, Deng L (2003) Catalytic Asymmetric Cyanosilylation of Ketones with Chiral Lewis Base. J Am Chem Soc 125 9900... 

Abdur-Rashid, K. Faatz, M. Lough, A. J. Morris, R. H. Catalytic cycle for the asymmetric hydrogenation of prochiral ketones to chiral alcohols Direct hydride and proton transfer from chiral catalysts trans-Ru(H)2(diphosphine) (diamine) to ketones and direct addition of dihydrogen to the resulting hydridoamido complexes. ]. Am. Chem. Soc. 2001,123, 7473-7474. 

With the addition of a catalytic amount of (5)-Q ,Q -diphenyl-pyrrolidinemethanol, this reagent combination of NaBILj/TMSCl has been successfully utilized in the enantioselective reduction of various ketones. The chiral alcohols were produced in excellent yields and very high enantiomeric excess (eq 71). ... 

Because ketones are generally less reactive than aldehydes, cycloaddition reaction of ketones should be expected to be more difficult to achieve. This is well reflected in the few reported catalytic enantioselective cycloaddition reactions of ketones compared with the many successful examples on the enantioselective reaction of aldehydes. Before our investigations of catalytic enantioselective cycloaddition reactions of activated ketones [43] there was probably only one example reported of such a reaction by Jankowski et al. using the menthoxyaluminum catalyst 34 and the chiral lanthanide catalyst 16, where the highest enantiomeric excess of the cycloaddition product 33 was 15% for the reaction of ketomalonate 32 with 1-methoxy-l,3-butadiene 5e catalyzed by 34, as outlined in Scheme 4.26 [16]. 

An alkene activated by an electron-withdrawing group—often an acrylic ester 2 is used—can react with an aldehyde or ketone 1 in the presence of catalytic amounts of a tertiary amine, to yield an a-hydroxyalkylated product. This reaction, known as the Baylis-Hillman reaction, leads to the formation of useful multifunctional products, e.g. o -methylene-/3-hydroxy carbonyl compounds 3 with a chiral carbon center and various options for consecutive reactions. 

Synthesis of the prototype begins with Friedel Crafts acetylation of salicylamide ( ). Bromination of the ketone (25) followed by displacement with amine gives the corresponding ami noketone ( ). Catalytic hydrogenation to the ami noalcohol completes the synthesis of labetolol (24). The presence of two chiral centers at remote positions leads to the two diastereomers being obtained in essentially equal amounts. 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

The application of auxiliary control in the asymmetric Michael addition of chiral enolates derived from ketones is rare the only example known is the use of (27 ,37 )-2,3-butancdiol as an auxiliary. The ketal of (27 ,37 )-2,3-butanediol with 3-methyl-l,2-cyclohexanedione reacts with 3-buten-2-one using as base a catalytic amount of sodium ethoxide in ethanol195. 

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