Palladium asymmetric allylic substitutions

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 palladium-catalyzed asymmetric allylic substitution using seven different phosphano-oxazoline ligands at various ligand-to-metal ratios was also studied.112 An aluminum block containing 27 wells was placed in a dry box in which the reactions were carried out in parallel. Analyses were performed by conventional chiral GC equipped with an autosampler. Such a setup allowed about 33 catalyst evaluations per day. Apparently, only a few dozen were carried out in the study, resulting in the identification of a catalyst showing an ee-value of 74% in the reaction of 4-acyloxy-2-pentene with malonate.112 It is not clear whether further ligand diversification would lead to catalysts more selective than the record set in this case by the Trost-catalyst (92% ee).113... 

Palladium-catalyzed allylic substitution reactions are popular in the chemical community and the number of applications of the reaction, perhaps in particular for asymmetric procedures, continues to grow [53]. The efficiency of asymmetric chemistry is best described in terms of the enantiomeric excess (ee) of the reaction, and it... 

In sharp contrast to a fully developed asymmetric palladium-catalyzed allylic substitution as described in the previous sections of this chapter, similar reactions using transition metal complexes other than palladium have not yet been fully investigated and their application to organic synthesis is quite limited at the present. In this section, examples of Cu-, Ni-, Pt-, Rh-, Ir-, Ru-, Mo-, and W-catalyzed allylic alkylation are summarized including recent developments in this field. 

In an effort to extend the use of the Pyrphos-derived dendrimers to asymmetric Pd-catalyzed coupling reactions, strongly positive selectivity effects were observed upon going to very large multi-site chiral dendrimer catalysts. This enhancement of the catalyst selectivity was observed in palladium-catalyzed allylic substitutions, such as that displayed in Scheme 3, which are known to be particularly sensitive to small changes in the chemical environment of the active catalyst sites [17]. 

Three research groups discovered almost at the same time that non-C2-symmetrical oxazolines of the type 32 can be even more effective ligands for asymmetric catalysis than type 4 ligands (Fig. 11). For the palladium-catalyzed allylic substitutions on 62, record selectivities could be reached using 32 (X = PPhj) [30]. It seems that not only steric but also electronic factors, which cause different donor/acceptor qualities at the coordination centers of the ligand, seem to play a role here [31]. The reaction products can subsequently be converted to interesting molecules, for example 63 (Nu = N-phthalyl) can be oxidized to the amino acid ester 64 [32]. 

Planar chiral phosphaferrocene-oxazolines (379) constitute another family of complexes that are usefiil as ligands in asymmetric catalysis. Preparation of these takes advantage of a modified Friedel-Crafts acylation of (373) and an unusual conversion of the resulting trifluoromethyl ketone into an amide that is then cyclized to an oxazoline. The diastereomeric complexes thus formed are chromatographically separable and are used in a palladium-catalyzed asymmetric allylic substitution. Modification of this complex by using the anion derived from 3,4-dimethyl-2-phenylphosphole gives more... 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

Reactions with Sulfur Nucleophiles. The use of sulfur nucleophiles in palladium-catalyzed allylic substitution reactions is less well documented than that of carbon, nitrogen and oxygen nucleophiles. The asymmetric synthesis of allylic sulfones utilizing a catalytic phase transfer system has been used to produce (35)-(phenylsulfonyl)cyclohex-l-ene on a 45 g scale (eq 10). In many cases, it has been reported that allylic carbonates are more reactive than allylic acetates in asymmetric allylic substitution... 

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. ... 

Kellogg, R. M. Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and palladium-catalyzed allylic substitution reactions. Chemtracts 2002, 15, 69-73. 

Helmchen, G. Enantioselective palladium-catalyzed allylic substitutions with asymmetric chiral ligands. J. Organomet. Chem. 1999, 576, 203-214. 

Saitoh, A., Achiwa, K., Tanaka, K., Morimoto, T. Versatile Chiral Bidentate Ligands Derived from a-Amino Acids Synthetic Applications and Mechanistic Considerations in the Palladium-Mediated Asymmetric Allylic Substitutions. J. Org. Chem. 2000, 65, 4227 240. 

An S—P-type chiral phosphinooxathiane was developed as an effective ligand for palladium-catalyzed allylic substitution reactions [131]. A polymer-supported chiral phosphinooxathiane 208 was also prepared and applied to asymmetric alkylations and aminations of acetate 201 [132]. Enanhoselechvihes of up to 99% ee were obtained in asymmetric Pd-catalyzed allylic amination of acetate 201 using the polymeric catalyst prepared from a PS-diethylsilyl support (Scheme 3.68). 

Heterogeneous aquacatalytic palladium-catalyzed allylic substitution with nitromethane as the Cl nucleophile has been developed by Uozumi (Scheme 3.71). By using an amphiphilic PS-PEG polymer-supported chiral palladium complex, the asymmetric allyhc nitromethylation of cycloalkenyl esters proceeded smoothly in water. For example, when polymer-supported palladium complex 214 was employed in the asymmetric nitromethylation of cycloheptenyl carbonate 215... 

Allylic substitutions are among the most important carbon-carbon bond-forming reactions in organic synthesis. Palladium-catalyzed allylic substitutions and their asymmetric version have been extensively studied and widely used in a variety of total syntheses [78]. The palladium catalysis mostly requires soft nucleophiles such as malonate carbanions to achieve high stereo- and regioselectivity. 

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. 

A. Saitoh, K. Achiwa, K. Tanaka, and T. Morimoto, Versatile chiral bidentate ligands derived from a-amino acids. Synthetic applications and mechanistic considerations in palladium-mediated asymmetric allylic substitutions, J. Org. Chem., 65 (2000) 4227-4243. 

Synthesis and application in palladium-catalysed asymmetric allylic substitution... 

SYNTHESIS AND APPLICATION IN PALLADIUM-CATALYSED ASYMMETRIC ALLYLIC SUBSTITUTION OF ENANTIOPURE CYCLIC p-IMINOPHOSPHINE LIGANDS... 

In summary, a new simple method for the preparation of axially chiral diphosphine complexes has been developed. The presence of the planar chiral ferrocenyl unit avoids the need of resolution since only one diastereomer is formed in a metal complexation. The new ligand is useful for asymmetric palladium-catalysed allylic substitutions with malonates and amino derivatives (Schemes 1 and 2). 

Most of the asymmetric allylic substitution processes start from racemic allylic components rac-l-R (where for 1-R, R designates the general group of the compound, e.g. 1-Me is 1 with R = Me), which in the absence of chiral ligands form meso complexes of the type 2 with palladium(O). Since a nucleophile can attack at either of the two ends of the allylic component, the enantiomers 3-R and ent-3-R are formed. The degree of the enantioselecti-vity of a reaction depends on how well a chiral ligand in 2 can direct the attack of the nucleophile (Nu) to one of the two allylic termini. 

A new class of chiral amidine-phosphine and -sulfide hydrid ligands with a variety of modifications is used for the palladium mediated allylic substitutions of both acyclic and cyclic compounds [74] (Figure 3.5). High levels of asymmetric induction were achieved for both substrates. 

Some ferrocenylphosphine-amidine ligands (Figure 3.6) with central and planer chirality were prepared and their efficiency and diastereomeric impact in the palladium catalysed asymmetric allylic substitution were examined [75]. Up to 96% ee with 98% yield was achieved by the use of a ligand with a methyl-substituted ligand. 

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