Chiral enone acetal

The primary disadvantage of the conjugate addition approach is the necessity of performing two chiral operations (resolution or asymmetric synthesis) ia order to obtain exclusively the stereochemicaHy desired end product. However, the advent of enzymatic resolutions and stereoselective reduciag agents has resulted ia new methods to efficiently produce chiral enones and CO-chain synthons, respectively (see Enzymes, industrial Enzymes in ORGANIC synthesis). Eor example, treatment of the racemic hydroxy enone (70) with commercially available porciae pancreatic Hpase (PPL) ia vinyl acetate gave a separable mixture of (5)-hydroxyenone (71) and (R)-acetate (72) with enantiomeric excess (ee) of 90% or better (204). 

Photocycloaddition of ketene acetals with enones gives cyclobutanes which can be converted to cyclobutanones (see Section 1.3.2.3.). When a chiral ketene acetal was used, photocycloaddition with cyclopent-2-enone gave a low yield of the cycloadduct with only 30% enantiomeric excess.23... 

The above examples have presented a better induction effect when the chiral auxiliary was located at the enone molecule. Double auxiliary induction has been examined by Scharf and coworkers99. Systematic study on the photoaddition of chiral enones 203 to chiral ketene acetals 204 provides examples of matched (45% de) and mismatched (9% de) double stereo differentiation (Scheme 44). 

Patzel achieved a stereoselective synthesis of methylcarboxy-substituted pyrrolidines 149 by reaction of phenyl iminoester 147 with chiral enones 148 (Scheme 2.40).67 Silver acetate (15 mol%) and DBU (1.2 equiv) in THF was used as promoters for the reaction. In almost all cases, selectivity better than 95 5 was achieved. 

N, P ] and [P, P ] Aldehydes with an a-stereocenter exhibit unusually high diastereofacial preferences for the addition of silyl enol ethers and ketene acetals with Lewis acid assistance (81). Heathcock and Uehling found good levels of facial discrimination in the addition of silyl enol ethers to chiral enones (Scheme 38, Table 11) (82). With the more substituted silyl enol ether, only one diastereomeric addition product is obtained (Eq. [1], Scheme 38). Use of a prostereogenic silyl enol ether allows control over the relative... 

Diastereoselective [2+2] photocycloaddition of a polymer-supported cyclic chiral enone with ethylene has been reported (Scheme 12.33) [43]. The auxiliary was derived from (-)-8-(p-methoxyphenyl) menthol (87). Protection of the secondary alcohol and demethylation were carried out to give (-)-8-(p-hydroxyphenyl)menthyl acetate (88). An alkyl linker was introduced and finally loaded to poly (ethylene glycol) grafted Wang resin. Deprotection of the alcohol functionality was followed by esterification with cyclohexen-3-one-l-carboxylic acid to provide the chiral enone 89. The photochemical reaction with ethylene was performed by irradiating with light (k > 280 nm). Trifluoroacetic acid (TFA) or aqueous hydrolysis with... 

The goal of introducing a nucleophile to an enone 1,4 enantioselectively has been reported by the use of both chiral enones and chiral nucleophiles. The former strategy is exemplified by a synthesis of natural (-)-methyl jasmonate by the addition of an acetate enolate equivalent to a chiral... 

Michael addition of the reagent to enoates and enones occurs at low temperature (—50 to —78 °C) in the presence of catalytic amounts of various Lewis acids. A catalytic amount of triph-enylmethyl perchlorate (5 mol %) effectively catalyzes the tandem Michael reaction of ethyl acetate-derived silyl ketene acetal to a, -unsaturated ketones and the sequential aldol addition to aldehydes with high stereoselectivity.HgL mediates the Michael addition to chiral enones, followed by Lewis acid-mediated addition to aldehydes. The Michael-aldol protocol has been used for the stereoselective synthesis of key intermediates on the way to prostaglandins, compactin, and ML-236A (eq 19). ... 

The mechanism of the TiCL-mediated Michael addition of silyl ketene acetals has been investigated, and criteria for suppressing the electron transfer process have been devised. Chiral enones show good to excellent diastereofacial preference in TiCU-mediated reactions with silyl ketene acetals (eq 20). ... 

Q Chiral racemic y-alkyl-substituted enones the titanium(IV) chloride mediated addition of enol silanes and silylketene acetals to 7 shows high induced diastereoselection (diastereomeric ratios from 89 11 to more than 97 3) and the major isomer 8 results from addition of the enolsilane with ul topicity288. Re face attack on the S enantiomer of 7.)... 

Penzien and Schmidt reported the first absolute asymmetric transformation in a chiral crystal. [10] They showed that enone 4,4 -dimethylchalcone 1, although being achiral itself, crystallizes spontaneously in the chiral space group P2 2 2 (Scheme 1). When single crystals of this material are treated with bromine vapor in a gas-solid reaction, the chiral dibromide 2 is produced in 6-25% ee. In this elegant experiment, it is the reaction medium, the chiral crystal lattice, that provides the asymmetric influence favoring the formation of one product enantiomer over the other, and the chemist has merely provided a non-chiral solvent (ethyl acetate) for the crystallization and a nonchiral reagent (bromine) for the reaction. 

Research by M. Majewski et al. showed that the enantioselective ring opening of tropinone allowed for a novel way to synthesize tropane alkaloids such as physoperuvine. The treatment of tropinone with a chiral lithium amide base resulted in an enantioslective deprotonation, which resulted in the facile opening of the five-membered ring to give a substituted cycloheptenone. This enone was subjected to the Wharton transposition by first epoxidation under basic conditions followed by addition of anhydrous hydrazine in MeOH in the presence of catalytic amounts of glacial acetic acid. 

Unsaturated acetals undergo a similar process when NiClj and a chiral phosphine 58 are added." The reaction of enones with diethylzinc is catalyzed by CuCOTf) which is coordinated to 59. Rubidium prolinate acts both as a base and chirality elicitor in reactions involving nitroalkanes, and an azacrown ether constructed out of sugar also induces the... 

An ingenious extension of the Tsuji-Trost reaction was the cornerstone of Oppolzer s enantioselective synthesis of a heteroyohimbine alkaloid, (-t-j-B-isorauniticine (267) [117]. Substrate 263 was prepared from a commercially available glycinate equivalent by Malkylation, installation of the sultam chiral auxiliary followed by a sultam-directed C-alkylation. As illustrated in Scheme 48, the crucial double cyclization was accomplished by the treatment of 263 with Pd(dba), Bu,P, in the presence of carbon monoxide (1 atm) in acetic acid to give enone 264 and two other stereoisomers in a 67 22 11 ratio. In this case, an allyl carbonate, rather than an allyl acetate, was used as the allyl precursor. Since carbonate is an irreversible leaving group, formation of the n-allylpalladium complex occurs readily. In the presence of Pd(0), the allylic carbonate is converted into a n-allylpalladium complex with concurrent release of CO, and... 

During the photocycloaddition of 88 with cyclopentene (Reaction 1), the de of the major isomer 89 increased from 30% in nonpolar solvents up to 68% in a mixture of methanol and acetic acid. When prochiral enone 91 was irradiated in the presence of a cyclopentene linked to the 8-phenylmenthol (Reaction 2), the best selectivity was now obtained in nonpolar solvents. To explain this effect, it was proposed that the facial selectivity is high in every case and that the diastereoselectivity depends on an s-cis s-trans ratio of the conjugated esters influenced by hydrogen bonding [65]. Similar results were obtained with chiral... 

N, P ] and [P,P ] Heathcock and Uehling examined diastereofacial discrimination in the addition of achiral silyl ketene acetals to chiral, racemic a,/ -unsaturated ketones (82). The addition of ketene acetals 47.1-47.3 to enone 47.4 occurs with good selectivity (Scheme 47). For example, the addition of 47.1 gives essentially one diastereomeric 1,4-addition product, along with 8% of 1,2-addition product (Eq. [1]). With the prostereogenic ketene acetals in Eq. [2], the same 1,4-adduct predominates. In these cases, the selectivity shows a curious decrease relative to the addition of the same ketene acetals to simple prostereogenic enones (entry 2, Table 17) and relative to the less substituted 47.1. 

An intemnolecular [2+2] cycloaddition using an enantiomerically pure enone substrate is described by M. Demuth. His menthone derived bicyclic acetal adds to cyclopentene with high diastereoselectivity (with both diastereoisomers obviously being enantiomerically pure). This chiral auxiliary also has been used in several syntheses of (+) and (-)-grandisol, a potent aggregation pheromone of the boll weevil. 

A preliminary examination of asymmetric induction in photochemical [2 + 2] cycloaddition reaction of an enone to an alkene employed a chiral auxiliary attached to the alkene component74. The photocycloaddition of 2-cyclopentenone to the optically active ketene acetal 1 led both to oxetanes and cyclobutanes in the ratio 6.5 3.5 with a total yield of 60%. The m-[2C + 2C] addition of the chiral alkene I to 2-cyclopentenone was completely regioselective and gave four diastereomeric head-to-tail cycloadducts 2-4 in the ratio 6 29 33 32. 

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