Asymmetric allylation substrate reactions

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

As shown in Scheme 2.20, selective lithiation of substrate 2-87 by treatment with LDA in THF at -78 °C triggers an intramolecular Michael/intermolecular aldol addition process with benzaldehyde to give a mixture of diastereomers 2-90 and 2-91. 2-91 was afterwards transformed into 2-92, which is used as a chiral ligand for Pd-catalyzed asymmetric allylic substitution reactions [29]. 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

Racemic conduritol B acetates and carbonates provide very versatile substrates for asymmetric allylic substitution reactions. Re-... 

Baylis-Hillman carbonate is a good substrate for asymmetric allylic substitution reaction, and various nucleophiles have been involved in this transformation. As shown in Scheme 9.36, the intermediate 72 (mechanistically formed by Michael... 

Abstract This account describes the circumstances leading to our group s innovations in the area of decarboxylative asymmetric allylic alkylation reactions and the initial discovery of palladium phosphinooxazoline complexes as efficient enantioselective catalysts. This chapter also chronicles the growth of the methodology to include several substrate classes, the expansion of the project into several other reaction manifolds, and the use of these reactions in natural product synthesis. Finally, important contributions from other research groups involving related methods or products similar to the ot-quatemary products that are the focus of our studies, as well as future directions for asymmetric alkylation reactions, are discussed. 

The use of palladium(II) 7i-allyl complexes in organic chemistry has a rich history. These complexes were the first examples of a C-M bond to be used as an electrophile [1-3]. At the dawn of the era of asymmetric catalysis, the use of chiral phosphines in palladium-catalyzed allylic alkylation reactions provided key early successes in asymmetric C-C bond formation that were an important validation of the usefulness of the field [4]. No researchers were more important to these innovations than Prof. B.M. Trost and Prof. J. Tsuji [5-10]. While most of the early discoveries in this field provided access to tertiary (3°) stereocenters formed on a prochiral electrophile [Eq. (1)] (Scheme 1), our interest focused on making quaternary (4°) stereocenters on prochiral enolates [Eq. (2)]. Recently, we have described decarboxylative asymmetric allylic alkylation reactions involving prochiral enolates that provide access to enantioenriched ot-quatemary carbonyl compounds [11-13]. We found that a range of substrates (e.g., allyl enol carbonates,... 

Table 9 Allyl P-ketoester substrates in the asymmetric allylic alkylation reaction ...

Most asymmetric induction processes with Chital auxiliaries involve a stereo-differentiating reaction that affords one diastereomet as the primary product To obtain the desired enantiomer, the Chiral auxiliary must be removed Highly dia-stereoselective reactions between otganocoppet reagents and allylic substrates with... 

Hie use of tlie cliiral catalyst 19b for asymmetric allylic substitution of allylic substrates bas been studied in some deta d fSdieme 8.18) and, under ji-selective reaction conditions, asymmetric induction was indeed obtained [28, 34]. 

Asymmetric Allylation. One of the recent new developments on this subject is the asymmetric allylation reaction. It was found that native and trimethylated cyclodextrins (CDs) promote enantiose-lective allylation of 2-cyclohexenone and aldehydes using Zn dust and alkyl halides in 5 1 H2O-THF. Moderately optically active products with ee up to 50% were obtained.188 The results can be rationalized in terms of the formation of inclusion complexes between the substrates and the CDs and of their interaction with the surface of the metal. 

Systematic studies of the reactions of tartrate allyl-boronates with a series of chiral and achiral alkoxy-substituted aldehydes show that conformationally unrestricted a- and /f-alkoxy aldehyde substrates have a significant negative impact on the stereoselectivity of asymmetric allyl-boration. In contrast, con-... 

To investigate the effect of the substituents in the arenethiolate structure, four differently substituted copper arenethiolates, 25-28, were tested as catalysts, but very low ees were obtained in all cases [34]. The oxazolidine complex 26, developed by Pfaltz et al. [36] and used successfully in asymmetric conjugate addition reactions to cyclic enones, gave a completely racemic product with allylic substrate 20a. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

Asymmetric allylic C-H activation of more complex substrates reveals some intrinsic features of the Rh2(S-DOSP)4 donor/acceptor carbenoids [135, 136]. Cyclopropanation of trans-disubstituted or highly substituted alkenes is rarely observed, due to the steric demands of these carbenoids [16]. Therefore, the C-H activation pathway is inherently enhanced at substituted allylic sites and the bulky rhodium carbenoid discriminates between accessible secondary sites for diastereoselective C-H insertion. As a result, the asymmetric allylic C-H activation provides alternative methods for the preparation of chiral molecules traditionally derived from classic C-C bond-forming reactions such as the Michael reaction and the Claisen rearrangement [135, 136]. 

The first example of Pd-catalyzed enantioselective allylation to be reported was the reaction of l-(l -acetoxyethyl)cyclopentene and the sodium salt of methyl benzenesulfonylacetate in the presence of 10 mol % of a DIOP-Pd complex, which led to the condensation product in 46% ee (Scheme 85) (200). This reaction used a racemic starting material, but the enantioselection was not a result of kinetic resolution of the starting material, because the chemical yield was above 80%. However, in certain cases, the selectivity is controlled at the stage of the initial oxidative addition to a Pd(0) species. In a related reaction, a BINAP-Pd(0) complex exhibits excellent enantioselectivity the chiral efficiency is affected by the nature of the leaving group of the allylic derivatives (Scheme 85) (201). It has been suggested that this asymmetric induction is the result of the chiral Pd catalyst choosing between two reactive conformations of the allylic substrate. 

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