Asymmetric nucleophilic allylic

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

Asymmetric nucleophilic allylic substitution has rarely been studied in its heterogeneous version, probably because of the difficulties encoimtered in properly stabilizing and recycling Pd(0) species. Nevertheless, some promising examples have been pubhshed. Lemaire et al. [143] studied the activity and enantioselectivity of various chiral C2-diamines for the asymmetric Pd-catalyzed transformation of various allyl acetates. The structures tested are represented in Scheme 58. 

Keywords N,N-Containing ligands Asymmetric catalysis Cyclopropanation Diels-Alder reaction Nucleophilic allylic substitution... 

Helquist et al. [129] have reported molecular mechanics calculations to predict the suitability of a number of chiral-substituted phenanthrolines and their corresponding palladium-complexes for use in asymmetric nucleophilic substitutions of allylic acetates. Good correlation was obtained with experimental results, the highest levels of asymmetric induction being predicted and obtained with a readily available 2-(2-bornyl)-phenanthroline ligand (90 in Scheme 50). Kocovsky et al. [130] prepared a series of chiral bipyridines, also derived from monoterpene (namely pinocarvone or myrtenal). They synthesized and characterized corresponding Mo complexes, which were found to be moderately enantioselective in allylic substitution (up to 22%). 

Asymmetric nucleophilic addition of Jt-allyl molybdenum complex as the final route. 

We will discuss each topic below. Later, we will discuss the key reaction, asymmetric nucleophilic addition of a n-allyl Mo complex, in great detail. 

Asymmetric Nucleophilic Addition of a ir-Allyl Mo Complex route... 

A newly developed asymmetric nucleophilic addition of malonate to 7i-allyl Mo complex was the cornerstone for this preparative campaign. 

When we used asymmetric nucleophilic addition of malonate to the Mo tt-allyl complex in our first delivery, the Mo chemistry was not so clearly understood, and our application would be the first large scale example, to the best of our knowledge. Initially our contributions to Mo chemistry were two-fold (i) replacement of non-commercially available (EtCN)3Mo(CO)3 or (C7H8)Mo(CO)3 by more stable and inexpensive Mo(CO)6 by incorporation of proper pre-activating time (ii) simplified preparation of the chiral ligand. Even after we completed the project, we still had a strong interest in Mo chemistry. 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

Schulz E (2005) Use of JV,JV-Coordinaling Ligands in Catalytic Asymmetric C-C Bond Formations Example of Cyclopropanation, Diels-Alder Reaction, Nucleophilic Allylic Substitution. 15 93-148... 

MgBr2-mediated asymmetric nucleophilic addition of Grignard reagents and allyl-tributyltin to aldehydes bearing sugar-derived jS- or y-tetrahydropyranyloxy chiral auxiliaries designed to complex with MgBt2 has been achieved. ... 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

A variation on this asymmetric catalytic allylation scheme employed (3-diketones or (3-keto ester nucleophiles with allyl ethers and a palladium-DIOP catalyst.434 The chiral center generated is now one carbon removed from the allyl ligand. As a result, somewhat lower optical yields were observed (-10% equation 353). A variety of chiral phosphines were evaluated in the cyclization of (3-keto esters. Optical yields up to 48% were measured in these reactions435... 

Although a vast amount of research has been devoted to the asymmetric 7i-allylic subshtuhon of acyclic esters (e.g. 1,3-diphenylpropenyl esters) with carbon and nitrogen nucleophiles, studies on the catalytic asymmehic subshtuhon of cyclic... 

Asymmetric aquacatalytic allylic Cj-subshtuhon was also achieved with nitromethane as a Cl nucleophile by using the PS-PEG resin-supported 23-Pd catalyst in which, under water-based conditions, nitromethane did not explode even under basic conditions (Scheme 6.6) [16]. To the best of the present author s knowledge. 

Catalytic Asymmetric Nucleophilic Addition to Achiral Imines 27 Table 1.12 Allylation of hydrazones. 

Asymmetric hydroboration ofalkenes Asymmetric Nucleophilic Attack Transfer of Allylic Groups from Boron to Carbon... 

Reactions of chiral allylic boranes with carbonyl compounds Reactions of chiral allyl boranes with imines Asymmetric Addition of Carbon Nucleophiles to Ketones Addition of alkyl lithiums to ketones Asymmetric epoxidation with chiral sulfur ylids Asymmetric Nucleophilic Attack by Chiral Alcohols Deracemisation of arylpropionic acids Deracemisation of a-halo acids Asymmetric Conjugate Addition of Nitrogen Nucleophiles An asymmetric synthesis of thienamycin Asymmetric Protonation... 

Significant advances have been made in asymmetric nucleophilic additions to -ir-allyl palladium complexes using chiral ligands. Substitution of allylic acetates in the presence of the chiral phosphine hgand 224 (or other chiral phosphine ligands) can occur with very high levels of enantioselection (1.224). The reaction works best with diaryl-substituted allylic acetates. 

Kanai and colleagues developed an enantioselective synthesis of various 2-(2-hydroxyethyl)indole scaffolds via the amido-cupration of allenes followed by the asymmetric addition of carbonyl compounds. Treatment of allene 88 with a copper catalyst forms a stable and highly nucleophilic allyl-copper species, which then adds into benzaldehyde (89) to furnish indole 90. A range of carbonyl compounds are competent in the sequence, including aryl- and heteroaryl aldehydes, alkyl aldehydes, and aryl ketones. This is reported to be the first example of a combined catalytic indole generation and subsequent enantioselective addition of carbonyl compormds (14CS1585). 

Four reviews on allylic substitution reactions have been published. The first deals with the enantioselective allylic substitutions by carbon nucleophiles, in the presence of both palladium and non-palladium catalysts. The second reviews stere- 0 oselective allylic substitution reactions forming asymmetric C-C, C-N, and C-O bonds. The third review covers new developments in metal-catalysed asymmetric 0 allylic substitution reactions with heteroatom-centred nucleophiles. Several applications of this new methodology are included. Finally, the catalytic 5 2 and 5 2 reactions of allylic alcohols, most of which occur with a very high ee, have been reviewed. ... 

Cyanide addition to the lactamic carbonyl group has been described in a reaction in which the cyanide ion acts as a catalyst (Fig. 14).The intermediate acyl cyanide can be attacked by an added nucleophile (allylic, propargylic, benzylic alcohols, aniline, benzylmercaptan). Comparative experiments were carried out using more classical procedures, such as under catalysis by potassium cyanide with stirring at room temperature, and with sodium alkoxides at -78 C. This last method provides the highest yields, up to 95% in most of the cases tested, but the sonochemical method proceeds under less basic conditions. Both methods preserve the integrity of the asymmetric center. 

The first example of Pd-catalyzed asymmetric nucleophilic substitutions of chiral j8-sulfinyl allylic systems was reported in 1995. The reaction of a chiral olefinic sulfoxide (5s)-l with dimethyl sodiomalonate was carried out in THF at room temperature (r.t.) in the presence of Pd(OAc)2 (0.1 equiv) and a phosphine ligand (0.2 equiv), giving (5,5s)-(Z)-2 with 29-79% de (Scheme 1). The degree of the asymmetric induction was largely dependent on the phosphine ligand used. With dpph as a ligand, the highest enantioselectivity was obtained. 

The use of a prochiral nucleophile in allylic substitution reactions provides an additional opportunity for asymmetric indnction. Allyl acetate itself can be used as the electrophilic partner and the new stereogenic center is positioned further away from the allyl group (Scheme 28). 

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