Asymmetric allylic substitution reactions

In 2001, Imamoto et al. reported the preparation of novel chiral S/P-bidentate ligands containing a chirogenic centre at the phosphorus atom and their stereoinduction capability in palladium-catalysed asymmetric allylic substitution reactions (Scheme 1.14)." ... 

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]. 

Asymmetric allylic substitution reactions have been studied for many years because they provide valuable chiral compounds. Regardless of the alkylating agent used, there are two major goals in these reactions (i) to minimize the amount of Sn2 products, and (ii) to maximize the enantiomeric purity of the Sn2 products. Various approaches have been investigated to achieve these goals. Recently, the efforts of several research groups have been focused on the... 

The moderate ees obtained with the copper arenethiolate ligands discussed above prompted a search for new chiral ligands for use in asymmetric allylic substitution reactions. The binaphthol-derived phosphoramidite ligand 32, used successfully by Feringa et al. in copper-catalyzed 1,4-addition reactions [37], was accordingly tested in the reaction between 21 and n-BuMgl. 

Mechanistic studies showed that metalacycle la is competent to be a catalyst in asymmetric allylic substitution reactions. The reaction of benzylamine with methyl ciimamyl carbonate catalyzed by a mixture of LI and [Ir(COD)Cl]2 occurs with an induction period and forms product in 84% yield and 95% ee, whereas the same reaction catalyzed by a mixture of metalacycle la and [Ir(COD)Cl]2 occurs without an induction period in just 2 hours to form the substitution product in 81% yield and 97% ee. The latter reaction was conducted with added [Ir(COD)Cl]2 to trap the -bound LI after dissociation. This ligand must dissociate to provide a site for oxidative addition of the allylic carbonate. 

Whereas Pd-catalyzed asymmetric allylic substitution reactions, with carbon as well as with heteronucleophiles, are widespread in stereoselective catalysis, it seems unusual that sulfur nucleophiles are less commonly used. Therefore we tested our ligands in such a reaction. We employed ligands 2 and 3 successfully in the reaction of racemic 3-methoxycarbonyloxyhept-4-ene with lithium t-butylsulfinate in the presence of 1.5 mol% of Pd2dba3 and 4.5 mol% of the ligands. In all cases full conversion was achieved, but with marked differences in the product selectivities (Scheme 1.4.9, Table 1.4.7). 

Scheme 5. Diversity-based approaches used in the late nineties in connection to the development of catalytic asymmetric allylic substitution reactions...

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

Optically active ferrocenylbisphosphines, (/J)-N,iV-dimethyl-l-[(5)-1, 2-bis(diphenylphosphino)ferrocenyIJethylamine [(/J)-(5)-BPPFA] and its derivatives, are efficient chiral bisphos-phine ligands for rhodium-catalyzed asymmetric hydrogenation, palladium-catalyzed asymmetric allylic substitution reactions, and gold-catalyzed asymmetric aldol-type reactions of a-isocyano carboxylates. ... 

Intramolecular asymmetric allylic substitution reactions have been applied to the synthesis of optically active cyclic compounds. The high efficiency of the dihydroxylated ferrocenylphosphine 8b has been shown in the cyclization of 2-butenylene dicarbamates 52 to form optically active 4-vinyl-2-oxazolidones 53, which are... 

Recently even asymmetric allylic substitution reactions using optically active Pd catalysts have become known. - An example of an intramolecular allylic substitution with nitrogen is seen in equation (22). 

MeO-PEG-supported soluble polymeric chiral ligands 204 were synthesized and utilized in various asymmetric allylic substitution reactions (Scheme 3.66) [129]. 

Figure 7.11 Chiral phosphorous ligands for asymmetric allylic substitution reactions.

The extraction concept is also applicable to sophisticated syntheses of fine-chemicals as recently shown by Ohe, Uemura and co-workers [35], They prepared a novel amphiphilic phosphinite-oxazoline chiral ligand based on D-glucosamine. The corresponding palladium complex was an efficient catalyst for asymmetric allylic substitution reactions and could be recycled by simple acid/base extraction and reused in the second reaction without loss of enantioselectivity. 

Nemoto and Hamada [50] has described the development of a new class of chiral phosphorus ligand - aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs - and their application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation was initially examined in detail using diaminophosphine oxides 77, resulting in the highly enantioselective construction of quaternary stereocenters. With the use of the Pd-DIAPHOX catalyst system, asymmetric allylic alkylation, asymmetric allylic amination, and enantioselective construction of quaternary carbons were achieved with high ee (up to 97-99% in many cases) (Scheme 24). 

Nemoto T, Hamada Y (2007) Pd-catalyzed asymmetric allylic substitution reactions using P-chirogenic diaminophosphine oxides DIAPHOXs. Chem Record 7 150-158... 

For reviews on Ir-catalyzed asymmetric allylic substitution reactions (a) H. Miyabe and Y. Takemoto, Synlett, 2005,1641 (b) R. Takeuchi and... 

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... 

Ir-Catalyzed Asymmetric Allylic Substitution Reactions - Fundamentais and Appiications in Naturai Products Synthesis... 

Tomohiro, H., Koji, Y., Kouichi, O. and Uemnra, S., A novel amphiphiUc chiral Ugand derived from d-glucosamine. Application to palladium-catalyzed asymmetric allylic substitution reaction in an aqueous or an organic medium, allowing for catalyst recycling, /. Org. Chem., 2000,65, 5197-5201. 

Palladium-catalyzed Allyllation Reactions. Palladium-catalyzed asymmetric allylic substitutions by soft nucleophiles are an extensively studied research area in organic chemistry with huge advances in ligand development and enantiocontrol seen in the past two decades. A typical asymmetric allylic substitution reaction with malonate is shown in eq 29. Diastereo- and enan-tioselective allylation of substituted nitroalkanes has also been reported. BSA has been used as a standard base in these reactions and functions satisfactorily. 

Geurts K, Fletcher SP, van Zijl AW, Minnaaid AJ, Feiinga BL (2008) Copper catalyzed asymmetric allylic substitution reactions with organozinc and Grignaid reagents. Pure Appl Chem 80 1025-1037... 

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