Ketenes, prochiral

Alternative catalytic asymmetric acylation reactions studied prochiral silyl imi-noketenes 89 [110] (Fig. 44, top) and silyl ketene acetals 90 [111, 112] (Fig. 44, middle), leading to the formation of quaternary stereocenters. Furthermore, the... 

In addition, azaferrocene catalyst 8 has been utilized by Fu and co-workers to perform enantioselective additions of alcohols to prochiral ketenes [51]. Aryl alkyl ketenes are substituted with MeOH to give a-aryl ester products in good enantioselectivities and very good yields, with higher enantiomeric excesses obtained for products with larger alkyl groups (Scheme 12). Use of 2,6-di-f-butylpyridinium triflate as a proton shuttle substantially enhances the enanti-... 

Alkaloid-catalyzed addition of methanol to a prochiral ketene by Pracejus et al. (ref. 11) ... 

This chapter covers the kinetic resolution of racemic alcohols by formation of esters and the kinetic resolution of racemic amines by formation of amides [1]. The desymmetrization of meso diols is discussed in Section 13.3. The acyl donors employed are usually either acid chlorides or acid anhydrides. In principle, acylation reactions of this type are equally suitable for resolving or desymmetrizing the acyl donor (e.g. a meso-anhydride or a prochiral ketene). Transformations of the latter type are discussed in Section 13.1, Desymmetrization and Kinetic Resolution of Cyclic Anhydrides, and Section 13.2, Additions to Prochiral Ketenes. 

High reactivity was observed for 21b, and 21a was found to be the most selective. In the presence of 10 mol% 21a selectivity factors as high as 6.5 were observed with racemic 1-(1-naphthyl)ethanol as substrate (Scheme 12.6) [18]. The TBS analog of 21a was found to be good catalyst for asymmetric addition of methanol to a variety of prochiral aryl alkyl ketenes [18]. The catalytic asymmetric addition of achiral alcohols to prochiral ketenes is discussed in Section 13.2. 

Attempts to convert prochiral ketenes such an 33 (Scheme 13.15) into enantio-enriched derivatives of a-chiral carboxylic acids (34, Scheme 13.15) are among the earliest examples of asymmetric nucleophilic catalysis in general. 

Pioneering work by Pracejus et al. in the 1960s, using alkaloids as catalysts, afforded quite remarkable 76% ee in the addition of methanol to phenylmethyl-ketene [26-29]. In 1999 Fu et al. reported that of various planar-chiral ferrocene derivatives tried, the azaferrocene 35 performed best in the asymmetric addition of methanol to several prochiral ketenes [30, 31]. In the presence of 10 mol% catalyst 35 (and 12 mol% 2,6-di-tert-butylpyridinium triflate as proton-transfer agent), up to 80% ee was achieved (Scheme 13.16). 

Pracejus et al. also demonstrated that diastereoselective addition of chiral amines to prochiral ketenes is possible [28, 32, 33] whereas attempts to catalytically produce enantiomerically enriched amides were frustrated by rapid uncatalyzed ad-... 

The alkaloid-catalyzed addition of alcohols to prochiral ketenes is one of the very first examples of catalytic asymmetric synthesis. In pioneering work by Pracejus in the 1960s quite remarkable 76% ee was achieved and it was not until 1999 that substantial improvement of enantioselectivity in catalytic asymmetric addition of O- and N-nucleophiles to prochiral ketenes was reported. In particular, the chiral... 

Additions to prochiral ketenes [13.2] Desymmetrization of meso-diols [13.3] Desymmetrization of meso-epoxides [13.4]... 

The original assignment of the absolute configuration (3S) for products 12 based on a comparison of the optical rotation value with a reported one for the phenyl derivative [27] must be considered uncertain. It would contradict the preferred attack of the nucleophile from the unshielded back side and the stereoselectivity observed in the reaction of A -galactosyl imines 7 with prochiral bis-silyl ketene acetals [28]. N-Galactosyl P-amino acids 13 are produced from bis-silylketene acetals in high yields and excellent diastereoselectivity (Scheme 10). The configuration at the P-position is R. 

Yamamoto et al. reported full research details on catalytic enantioselective protonation under acidic conditions in which prochiral trialkylsilyl enol ethers and ketene bis(trialkyl)silyl acetals were protonated by a catalytic amount of Lewis acid assisted Bronsted acid (LBA15 or 16) and a stoichiometric amount of 2,6-dimethylphenol as an achiral proton source [20]. 

The cycloaddition of chiral (-)menthylcarbodiimide with prochiral ketenes affords chi-rally selective cycloadducts In the reaction of an optically active alcohol with dicy-clohexylcarbodiimide complete inversion of the configuration occurs after hydrolysis. " Treatment of arenesulfenic acids with alcohols, thiols or secondary amines in the presence of optically active carbodiimides affords the corresponding optically active arenesulfenic acid derivatives. DCC is used to convert an optically active selenoxide into the corresponding optically active selenimide with TsNHa. ... 

In the reaction of carbodiimides with chiral substituents with prochiral ketenes, /3-lactams are obtained in a highly diastereoselective rnanner. ... 

This technology has been apphed as part of the total synthesis of myx-alamide A (Scheme 56) [139]. The stereoselective aldol reaction between aldehyde 218 and the propionate 219 dehvered, after reduction, protection, and acylation, ester 220 as a single isomer. After -silyl ketene acetal formation a [3,3]-sigmatropic rearrangement accompanied by 1,3-chirality transfer took place. This, together with the uniform prochirality at the double bonds of the... 

Scheme 18). The reaction occurs at the most nucleophilic imine bond C=NMe > 0=NBu > G—N-aryl > d —NSiRs (equation 42). The reaction takes place by an ionic mechanismin which ring closure is the slowest step. In the reaction of prochiral ketenes with chiral carbodiimides, ring closure creates a new chiral center with good selectivity (equation 43). 

The nucleophilic addition on substituted ketenes is a well-known method to generate a prochiral enolate that can be further protonated by a chiral source of proton. Metallic nucleophiles are used under anhydrous conditions therefore, the optically pure source of proton must be added then (often in a stoichiometric amount) to control the protonation. In the case of a protic nucleophile, an alcohol, a thiol, or an amine, the chiral inductor is usually present at the beginning of the reaction since it also catalyzes the addition of the heteroatomic nucleophile before mediating the enantioselective protonation (Scheme 7.5). The use of a chiral tertiary amine as catalyst generates a zwitterionic intermediate B by nucleophilic addition on ketene A, followed by a rapid diastereoselective protonation of the enolate to acylammonium C, and then the release of the catalyst via its substitution by the nucleophile ends this reaction sequence. 

Pracejus also studied the tandem nucleophilic addition/diastereoselective protonation of optically pure (S)-phenylethylamine on phenylmethylketene [11], With the aim of synthesizing amino acids and their derivatives, Calmes and coworkers reinvestigated the reaction of prochiral ketenes (generated in situ from acid chorides in the presence of a tertiary amine) with (R)-pantolactonc, an a-hydroxylactone [12], The authors have shown that the diastereoselectivity is dependent on the base used. Particularly, triethylamine and quinuclidine afforded complementary results and the diasteromeric ratios observed with quinuclidine suggest that the high stereoselections could be observed in nucleophilic additions to prochiral ketenes in the presence of cinchona alkaloids. 

Despite the obvious potential of cinchona alkaloids as bifunctional chiral catalysts of the nucleophilic addition/enantioselective protonation on prochiral ketenes, no further contribution has appeared to date and only a few papers described this asymmetric reaction with other catalysts [13], When the reaction is carried out with soft nucleophiles, the catalyst, often a chiral tertiary amine, adding first on ketene, is covalently linked to the enolate during the protonation. Thus, we can expect an optimal control of the stereochemical outcome of the protonation. This seems perfectly well suited for cinchona analogues and we can therefore anticipate successful applications of these compounds for this reaction in the near future. 

Asymmetric protonations of prochiral ketenes, metal enolates or enamines are performed with chiral alcohols, amines or amine salts [552], Recently, good enantiomeric excesses ( 80%) have been obtained in ketene protonations with the following a-hydroxyesters methyl (R)- or ([Pg.88]

L. Banfi, S. Cardani, D. Potenza and C. Scolastico, Tetrahedron, 1987, 43, 2317 G. Guanti, L. Banfi, E. Narisano and C. Scolastico, Tetrahedron Lett., 1985, 26, 3517. For the addition of nitrogen-substituted silyl ketene acetals to prochiral aldehydes (simple stereoselection), see T. Oesterle and G. Simchen, Synthesis,... 

Largely stimulated by the synthesis of 3-lactam antibiotics, there have been widespread investigations into the stereochemical aspects of imine condensations, mainly involving reactions of enolates of carboxylic acid derivatives or silyl ketene acetals. In analogy to the aldol condensation, stereoselectivity of imine condensations will be discussed in terms of two types in this chapter (i) simple dia-stereoselectivity or syn-anti selectivity, when the two reactants are each prochiral (equation 12) and (ii) diastereofacial selectivity, when a new chiral center is formed in the presence of a pre-existing chiral center in one of the reactants (e.g. equation 13). The term asymmetric induction may be used synonymously with diastereofacial selectivity when one of the chiral reactants is optically active. For a more explicit explanation of these terms, see Heathcock s review on the aldol condensation. ... 

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