Asymmetric Heck-type reaction

In a very recent work, the Pd-catalysed cross-coupling reactions with arenediazonium salts under aerobic conditions in the presence of a chiral monothiourea ligand were reported (Scheme 25) [106]. Even if this Hgand bears four chiral centres, no test in asymmetric Heck-type reaction has been described so far. 

For an intramolecular asymmetric Heck-type reaction of alkenyl iodide 73 to form an optically active indolizidine derivative, a palladium catalyst coordinated... 

Sato, Y., Sodeoka, M. and Shibasaki, M. (1990) On the role of silver salts in asymmetric Heck-type reaction. A greatly imrpoved catatytic asymmetric synthesis of cis-decalin derivatives. 

A similar procedure was employed in the asymmetric Heck-type coupling of iodonium salt 81 with 2,3-dihydrofuran (Scheme 38) [65]. When carried out in the presence of the chiral bidentate ligand (R)-BINAP, this reaction afforded optically active (up to 78% ee) coupling product 82 in moderate yield. 

The palladium-catalyzed arylation and alkenylation of olefins, which were first discovered in the 1970 s by Heck (7,2) and Mizoroki (3) and have been often called the "Heck reaction", are versatile synthetic means for making a carbon-carbon bond. These reactions have been extensively used for organic synthesis during the past two decades (4-7). However, no reports on the "asymmetric Heck reaction" have been appeared until very recently. Shibasaki reported an asymmetric intramolecular cyclization of alkenyl iodides to give c/j-decalin derivatives of 80-91% ee (8-10). Overman reported an intramolecular cyclization of alkenyl triflate, giving a chiral quaternary carbon center of 45% ee (77). We report herein the first example of intermolecular asymmetric Heck-type arylation of cyclic olefins catalyzed by (7 )-BINAP-coordinated palladium complexes (Scheme 1) (12,13). 

A wide variety of synthetic processes have been rendered asymmetric through the use of a chiral catalyst. In addition to the types of reaction described above, chiral transition metal catalysts have been used to influence the stereochemical course of isomerization, cyclization, and coupling reactions. As an example, an approach towards the natural product (-)-epibatidine (158) was recently reported by Namyslo and Kaufmann (166). Epibatidine is a potent analgesic and a nicotinic receptor agonist. The synthesis involves an asymmetric Heck-type hydroarylation between the bicyclic alkene (155) and pyridyl iodide (156). A number of bidentate chiral li-... 

In the same year, a series of Ci-symmetric chiral triazolium Pd(II) complexes were prepared by Enders et al. As typically reported with the use of Ci-symmet-ric ligands, their NHC-metal complexes were obtained as diastereomeric mixtures due to the restricted rotation around the carbene-metal bond [6]. Without further elaboration, the authors stated that these complexes were used in an enantioselective Heck-type reaction achieving low asymmetric inductions. Soon thereafter, the authors investigated the coordination behavior of chiral triazolium salts 35 with [Rh(COD)Cl]2 and obtained a mixture of axially chiral complexes 36 with a diastereomeric excess of up to 94% (Scheme 3.20). These complexes were used as catalysts in asymmetric hydrosilylation reactions, achieving up to 44% ee for aromatic and ahphatic ketones [38,39]. 

To account for the differences in reactivity and enantioselectivity observed in Heck reactions of unsaturated triflates and halides, two distinct mechanistic pathways have been proposed (as shown in the margin). The "cationic" pathway is generally invoked to describe asymmetric Heck reactions of unsaturated triflates or halides in the presence of Ag(I) or T1(I) additives. In the absence of such additives the Heck reaction is expected to proceed through a "neutral" reaction pathway. The modest enantioselectivity often observed in Heck reactions of this type has been attributed to the formation of a neutral palladium-alkene complex by partial ligand dissociation. ... 

The first examples of asymmetric Heck cyclizations that form quatemaiy carbon centers with high enantioselectivity came from our development of an asymmetric synthesis of the pharmacologically important alkaloid (—)-physostigmine (184) and congeners (Scheme 6-31) [68]. In the pivotal reaction, (Z)-2-butenanilide iodide 182 was cyclized with Pd-(5)-BINAP to provide oxindole 183 in 84% yield and 95% ee after hydrolysis of the intermediate silyl enol ether. With substrates of this type, cyclizations in the presence of halide scavengers took place with much lower enantioselectivity [68]. 

Catalytic asymmetric arylation of alkenes.4 This arylation can be effected by a Heck-type arylation of 2,3-dihydrofuran with an aryl triflatc catalyzed by Pd(OAc)2/(R)-BINAP in the presence of 1,8-bis(dimelhylamine)naphthalcnc (proton sponge) as base. This reaction was used to prepare an antagonist (4) of platelet activating factor. 

Transition metal enolate complexes have been prepared with most or all transition metals, and the enolate ligands have been shown to adopt a variety of bonding modes. Bofli early and late transition metal enolate complexes are intermediates in a number of important catalytic processes. Early transition metal enolates are important intermediates in asymmetric aldol reactions that exploit the Lewis acidic character of early metals. Late transition metal enolates are intermediates in aldol and Michael addition processes, -Saegusa oxidations,Heck-type processes, catalytic asymmetric conjugate additions, - and cross coupling of enolate nucleophiles. - ... 

In 1999, Mikami s group reported the first example of an intermolecular asymmetric Fujiwara-Moritani reaction of benzene with cyclic alkenes using a Pd catalyst co-ordinating to a chiral sulfonylamide-oxazoline ligand (Scheme 7.24). With PhCOs Bu as the oxidant, the coupling reaction occurred with moderate enantioselectivity (up to 49% ee), although the chemical yield was low. The reaction is considered to involve the formation of a phenyl-Pd species via electrophilic C-H substitution by Pd(ii), and Heck-type cyclization followed by re-oxidation of the resultant Pd(0) species. 

After the initial reports by Banerjee et al. on the intramolecular reductive Heck reaction in the synthesis of abeo-abietane-type diterpenoids, " Node et al. adopted the intramolecular asymmetric Heck reaction for the synthesis of (—)-dichroanal B, (—)-dichroanone, and taiwaniaquinone H. Palladium cyclization of triflate 18 using (/ )-Synphos as ligand and successive hydrogenation afforded the key intermediate (5)-19 in 86% yield and 94% ee. Significantly, both E/Z triflates of 18 gave the desired Heck product 19 indicating an equilibrium between the two isomers (Scheme 13.7). 

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