Stereoselective allylic alkylations

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

Martin et al. disclosed that [Rh(CO)2Cl]2 catalyzes highly regio- and stereoselective allylic alkylation using a-substituted sodiomalonates. The new C - C bond was formed at the carbon bearing the leaving group [22]. Owing to the known ability of Rh(I) complexes to catalyze carbocyclizations such as the Pauson-Khand reaction (PKR) [23,24] or [5 + 2] cycloadditions [25], Martin anticipated that the aforementioned reaction could be the first step of... 

Scheme 12.15 Regio- and stereoselective allylic alkylation of a chelated ester enolate [16].

Palladium remains the most widely recognized transition metal to effect stereoselective allylic alkylation reactions. Consequently, diastereoselective and enantioselective Pd-catalyzed processes are extensively discussed in Sections 14.2 and 14.3. More recent advances in the field of metal-catalyzed al-lylation reactions include the use of chiral iridium complexes, dealt with in Section 14.4 [33, 34]. Section 14.5 describes selected stereoselective copper-catalyzed SN2 -allylation reactions [33, 35-37], while a brief presentation of allylation reactions with other transition metals including Mo and Rh is given in Section 14.6 [8, 13, 33, 38, 39]. The closing Section 14.7 deals with selected methods for asymmetric ring-opening reactions of unsaturated heterocycles [38, 40, 41]. 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

The catalytic enantioselective addition of vinylmetals to activated alkenes is a potentially versatile but undeveloped class of transformations. Compared to processes with arylmetals and, particularly alkylmetals, processes with the corresponding vinylic reagents are of higher synthetic utility but remain scarce, and the relatively few reported examples are Rh-catalysed conjugate additions. In this context, Hoveyda et al. reported very recently an efficient method for catalytic asymmetric allylic alkylations with vinylaluminum reagents that were prepared and used in Thus, stereoselective reactions... 

Allyl acetates are more commonly used as electrophiles for the palladium-catalyzed allylic alkylation than allylic nitro compounds.20 However, the reaction of allylic nitro compounds has found wider applications. Allylic nitro compounds are readily available by nitration of alkenes. The regio- and stereoselective introduction of electrophiles and nucleophiles into alkenes is possible as outlined in Eq. 7.19. In fact, this strategy is applied to the synthesis of terpenoids.21... 

Tab. 11.8 Representative examples of the regio- and stereoselective tandem n-allyl alkylation and PK reaction.

An NOE study of the intermediate [Pd(ti -PhCHCHCHPh)(Binap)], 82, thought to be involved in the Pd-catalyzed allylic alkylation of a 1,3-diphenylpropene, revealed that two phenyl rings, one from the auxiliary, D, and one from the substrate, F, are forced to take up parallel positions, i.e, they are 7i-stacked, as shown in 83 [103]. Since the ti-stacking is repulsive, and thus selectively weakens one of the two Pd-C(allyl) bonds, the reaction becomes stereoselective. The D and F rings do not show inter-ligand NOEs. 

The chiral nonracemic bis-benzothiazine ligand 75 has been screened for activity in asymmetric Pd-catalyzed allylic alkylation reactions (Scheme 42) <20010L3321>. The test system chosen for this ligand was the reaction of 1,3-diphenylallyl acetate 301 with dimethyl malonate 302. A stochiometric amount of bis(trimethylsilyl)acetamide (BSA) and a catalytic amount of KOAc were added to the reaction mixture. A catalytic amount of chiral ligand 75 along with a variety of Pd-sources afforded up to 90% yield and 82% ee s of diester 303. Since both enantiomers of the chiral ligand are available, both R- and -configurations of the alkylation product 303 can be obtained. The best results in terms of yield and stereoselectivity were obtained in nonpolar solvents, such as benzene. The allylic alkylation of racemic cyclohexenyl acetate with dimethyl malonate was performed but with lower yields (up to 53%) and only modest enantioselectivity (60% ee). 

Intermediate for the preparation of vinyloxazolines for stereoselective nitrile oxide cycloaddition Intermediate for polymer 225 supported catalyst for asymmetric allylic alkylation... 

As described above, the phosphorus atom generally plays an important role for the stereoselection in the allylic alkylation. However, other types of chelating compotmds not having phosphorus are also revealed to work as effective chiral ligands. Some N-S chelating ligands 99-103 bearing an oxazoline moiety provide an excellent enantioselectivity... 

Considerable attention was given to the stereochemistry for the alkylation of metal enolates of y-butyrolactones during the past 1980 s decade. It is well recognized that electrophihc attack on the enolates of -substituted y-butyrolactones is controlled exclusively by the -substituent leading to the trans addition products . However, Iwasaki and coworkers reported the reverse diastereofacial differentiation in the alkylation of the enolates of a, S-dibenzyl-y-butyrolactones. These authors proposed that the factor controlling the selectivity in this case was allylic strain. Also, y-substituted y-lactones give stereoselective trans alkylation . ... 

Evans and Leahy reported on a method for the rhodium-catalyzed allylic alkylation using copper enolates, generated by transmetalation of the corresponding lithium enolates (equation 19). These enolates are softer and less basic nucleophiles than lithium enolates and therefore problems typically associated with enolate nncleophiles in metal-allyl chemistry can be avoided. A copper(I) enolate, derived from acetophenone derivative 63, was used as nucleophile in a regio- and stereoselective rhodinm-catalyzed alkylation of the in situ activated allylic alcohol 62. Thereby, the synthesized ketone 64, a key intermediate in the total synthesis of (—)-sugiresinol dimethyl ether (65), was produced as the only detectable regioisomer with complete conservation of enantiomeric excess. 

Braum M, Meier T. New developments in stereoselective palladium-catalyzed allylic alkylations of preformed enolates. 

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