Allylic substitutions enantioselective Tsuji allylation

The formation of chromane derivatives has also been realised in the palladium catalyzed intramolecular nucleophilic substitution of allyl carbonates (Tsuji-Trost reaction). In most cases the reaction is accompanied by the formation of a new centre of chirality. Using Trost s chiral ligand the ring closure was carried out in an enantioselective manner. The asymmetric allylation of the phenol derivative shown in 4.20. was achieved both in good yield and with excellent selectivity.23... 

One distinguishes palladium(0)- and palladium(ll)-catalysed reactions. The most common palladium(O) transformations are the Mizoroki-Heck and the cross-coupling transformations such as the Suzuki-Miyaura, the Stille and the Sonogashira reactions, which allow the arylation or alkenylation of C=C double bonds, boronic acid derivates, stan-nanes and alkynes respectively [2]. Another important palladium(O) transformation is the nucleophilic substitution of usually allylic acetates or carbonates known as the Tsuji-Trost reaction [3]. The most versatile palladium(ll)-catalysed transformation is the Wacker oxidation, which is industrially used for the synthesis of acetaldehyde from ethylene [4]. It should be noted that many of these palladium-catalysed transformations can also be performed in an enantioselective way [5]. 

In their enantioselective total synthesis of the alkaloid cephalotaxine (246), Tietze and Schirok [127] used a combination of a Tsuji-Trost and a Mizoroki-Heck reaction (Scheme 8.62). It was necessary to adjust the reactivity of the two palladium-catalysed transformations to allow a controlled process. Reaction of 243a using Pd(PPh3)4 as catalyst led to 244, which furnished 245 in a second palladium-catalysed reaction. In this process, the nucleophilic substitution of the allylic acetate is faster than the oxidative addition of the arylbromide moiety in 243a however, if one uses the iodide 243b, then the yield drops dramatically due to an increased rate of the oxidative addition. 

Thanks to the fundamental studies of Tsuji, Trost, and others, palladium-catalyzed allylic substitution has become a versatile, widely used process in organic synthesis [40]. The search for efficient enantioselective catalysts for this class of reactions is an important goal of current research in this field [41]. It has been shown that chiral phosphine ligands can induce substantial enantiomeric excesses in Pd-catalyzed reactions of racemic or achiral allylic substrates with nucleophiles [42]. Recently, promising results have also been obtained with chiral bidentate nitrogen ligands [43]. We have found that palladium complexes of neutral aza-semicorrin or methylene-bis(oxazoline) ligands are effective catalysts for the enantioselective allylic alkylation of l,3-diphenyl-2-propenyl acetate or related substrates with dimethyl malonate (Schemes 18 [25,30] and 19 [44]). 

Transition metal-catalyzed allylic substitution reactions with carbon nucleophiles are among the most important carbon-carbon bond formation methods in modem organic synthesis, because of their broad substrate scope under mild reaction conditions. In addition, they are applicable to enantioselective reactions, as well as exhibiting versatility towards the alkene functionality adjacent to the chiral centre for stereoselective derivatization. Tsuji-Trost allylic substitution, involving a (Ti-allyl) metal intermediate, has provided a particular advance in this regard [34, 35]. Most recently, Sawamura et al. [36, 37] have improved the regioselectivity of this reaction with unsymmetrically substituted allylic esters, and thus opened a new approach to sertraline. 

The protocols for the utilization of ketone-derived silyl enol ethers in Tsuji-Trost reactions were preceded by a report of Morimoto and coworkers on the enantioselective allylation of sUyl ketene acetals 88. Without external activation, they reacted with the allylic substrate 19d in the presence of the palladium complex derived from the amidine ligand 89 to give y,5-unsaturated esters 90 in moderate chemical yield but high enantiomeric excess (Scheme 5.29) [46]. Presumably, the pivalate anion hberated during the oxidative addition functions as an activator of the silyl ketene acetal. The protocol is remarkable in view of the fact that asymmetric allylic alkylations of carboxylic esters are rare. Interestingly, the asymmetric induction originates from a ligand with an uncomplicated structure. The protocol seems however rather restricted with respect to the substitution pattern of allylic component and sUyl ketene acetal. 

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