Stille coupling enantioselective reactions

In 1998, Yamamoto et al. reported the first catalytic enantioselective allylation of imines with allyltributylstannane in the presence of a chiral 7i-allylpalladium complex 23 (Scheme 9) [15]. The imines derived from aromatic aldehydes underwent the allylation with high ee values. Unfortunately, the allylation reaction of aliphatic imines resulted in modest enantioselectivities. They proposed that a bis-Jt-allylpalladium complex is a reactive intermediate for the allylation and reacts with imines as a nucleophile. The bis-Jt-allylpalladium complex seemed the most likely candidate for the Stille coupling [16]. Indeed, the Stille coupling reaction takes place in the presence of triphenylphosphine even if imines are present, whereas the allylation of imines occurs in the absence of the phosphine [17]. They suggested the phosphine ligand played a key role in controlling the... 

The first enantioselective total synhesis of (-)-strychnine was achieved by L.E. Overman and co-workers. The carbon skeleton of the main precursor for the key aza-Cope rearrangementMannich cyclization was assembled by applying a Pd ° -catalyzed carbonylative Stille coupling reaction. Thus, the cyclic vinylstannane was coupled with the triazinone-protected ortho-iodoaniline to afford 80% yield of the aromatic enone using Pd2(dba)3 as the catalyst in the presence of carbon monoxide. 

The enantioselective syntheses of ircinol A (38) and the related manzamine alkaloids ircinal A and manzamine A were accomplished by Martin (Scheme 5.4.9). The concise synthesis of ircinol A (38) highlights the strategy for assembling the tricyclic ABC ring core via a domino Stille coupling/Diels-Alder reaction. 

In most of the palladium-catalysed domino processes known so far, the Mizoroki-Heck reaction - the palladium(0)-catalysed reaction of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - has been apphed as the starting transformation accordingly to our classification (Table 8.1). It has been combined with another Mizoroki-Heck reaction [6] or a cross-coupling reaction [7], such as Suzuki, Stille or Sonogashira reactions. In other examples, a Tsuji-Trost reaction [8], a carbonylation, a pericyclic or an aldol reaction has been employed as the second step. On the other hand, cross-couphng reactions have also been used as the first step followed by, for example, a Mizoroki-Heck reaction or Tsuji-Trost reactions, palladation of alkynes or allenes [9], carbonylations [10], aminations [11] or palladium(II)-catalysedWacker-type reactions [12] were employed as the first step. A novel illustrative example of the latter procedure is the efficient enantioselective synthesis of vitamin E [13]. 

Heterogenization of homogeneous metal complex catalysts represents one way to improve the total turnover number for expensive or toxic catalysts. Two case studies in catalyst immobilization are presented here. Immobilization of Pd(II) SCS and PCP pincer complexes for use in Heck coupling reactions does not lead to stable, recyclable catalysts, as all catalysis is shown to be associated with leached palladium species. In contrast, when immobilizing Co(II) salen complexes for kinetic resolutions of epoxides, immobilization can lead to enhanced catalytic properties, including improved reaction rates while still obtaining excellent enantioselectivity and catalyst recyclability. 

The advantage of fluorescence-based assays is their high sensitivity. It is therefore perhaps surprising that few such systems have been developed for evaluating the enantioselectivity of enzyme-catalyzed reactions. Fluorescence as a detection method is used in an enzyme-coupled assay [26] (see Section 9.3.4.3) and in the capillary array electrophoresis [25] (see Section 9.3.6.5). If several substrates need to be screened simultaneously, fluorescence-based substrate arrays as enzyme fingerprinting tools can be used, although enantioselectivity still needs to be addressed [26e],... 

This is mainly due to the fact that by means of chiral ligands it is comparatively facile to transfer absolute stereochemical information to a cat-alytically active metal center. However, the success of some of these reactions (e.g. the Sharpless asymmetric epoxidation or the Noyori hydrogenation) must not hide the fact that the number of powerful transition metal-catalyzed C-C coupling reactions, which proceed reliably with high enantioselectivity, is still rather small. 

Han, X., Stoltz, B.M. and Corey, E.J., Cuprous chloride accelerated Stille reactions. A general and effective coupling system for sterically congested substrates and for enantioselective synthesis, J. Am. Chem. Soc., 121, 7600, 1999. 

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]. 

More than 20 years ago Stille and Tunney reported a Pd-catalysed coupling of achiral silylphosphines with aryl iodides. Bergman, Toste and Chan recently described a modification of this reaction as a new route to prepare P-stereogenic phosphines by enantioselective arylation of tertiary racemic silylphosphines (Scheme 6.28). 

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