Asymmetric Heck reactions, use

A novel phosphinito dipeptido ligand series were prepared, and fully characterized. These ligands readily form metal complexes with Pd(H) and Pt(II) precursors. The Pd(II) complexes were investigated for their suitability in asymmetric Heck reaction using 3,4-dihydrofuran as a substrate. 

The Heck reaction has proven to be an extremely useful method for the formation of C-C bond at a vinyl carbon centre. There are numerous reported examples of enantioselctive Pd catalyzed C-C bond forming reactions.10"13 Surprisingly, reports of Heck transformations using amino acid based phosphine, phosphinite ligands are rare. Recently Gilbertson reported a proline derived phosphine-oxozoline ligand in a catalytic asymmetric Heck reaction.5 In this paper we present some novel amino acids derived ligands as part of a catalytic system for use in asymmetric Heck reactions. 

Palladium-catalyzed arylation of olefins and the analogous alkenylation (Heck reaction) are the useful synthetic methods for carbon-carbon bond formation.60 Although these reactions have been known for over 20 years, it was only in 1989 that the asymmetric Heck reaction was pioneered in independent work by Sato et al.60d and Carpenter et al.61 These scientists demonstrated that intramolecular cyclization of an alkenyl iodide or triflate yielded chiral cyclic compounds with approximately 45% ee. The first example of the intermolecular asymmetric Heck reaction was reported by Ozawa et al.60c Under appropriate conditions, the major product was obtained in over 96% ee for a variety of aryl triflates.62... 

One active field of research involving the Heck reaction is asymmetric Heck reactions (AHR). The objective is to achieve enantiomerically-enriched Heck products from racemic substrates using a catalytic amount of chiral ligands, making the process more practical and economical Although intermolecular Heck reactions that occurred onto carbocyclic arenes are rare, they readily take place onto many heterocycles including thiophenes, furans, thiazoles, oxazoles,... 

A fluorous version of the chiral bis-phosphine BINAP has been developed for asymmetric Heck reactions [5], Several fluorous-derivatized binaphthols and BINAP derivatives have been reported, (Scheme 10.4) [6], The silane spacer group present in one of the ligands was used to maximize the percentage fluorine on the molecule. Even so, the partition coefficient1 between FC-72 (see Chapter 3) and benzene was only 2.85, and not surprisingly, the reuse of the catalyst was poor. 

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). 

In an interesting example of the first asymmetric Heck reaction,6 using sulfoxides as chiral auxiliaries, Carretero et al.145 have recently used a new chiral sulfoxide, obtained by the DAG methodology. The palladium-catalyzed arylations of 4-arylsulfinyl-2,3-dihydrofurans 102 have shown that the stereochemical outcome of the reaction is highly dependent on the substitution of the sulfoxide. Thus, independently of electronic substitution of the aryl iodide, different aryl sulfoxides... 

Excellent enantioselectivity and double-bond regioselectivity can be achieved in an asymmetric Heck reaction between 2,3-dihydrofuran and aryl triflates by using a combination of chiral diphosphine-oxazoline ferrocenyl ligand and Pd catalyst <03CEJ3073>, as shown below. Chiral diphosphine-containing (arene)tricarbonylchromium(O) complexes were also used as ligands for this reaction to obtain the 2,3-isomer, however, both the yield and enantioselectivity were modest <03TA1455>. 

A variety of chiral phosphine ligands are frequently used for asymmetric Heck reactions. The oxidative insertion is favored by basic ligands whereas bidentate ligands with a small bite angle enable good to excellent chirality transfer (>90 % ee). Some selected ligands which meet these requirements for asymmetric Heck reactions are shown in the margin. 

Figure 3-1 Some chiral ligands used in asymmetric Heck reactions (see Table 3-8).

Table 3-8 Some chiral li gands used in asymmetric Heck reactions [208] (Figure 3-1) ...

Intramolecular asymmetric Heck reactions. The usefulness of the As analog of BINAP as a ligand for the cyclization of iodoalkenylcyclohexadienes has been demonstrated. 

There has also been considerable interest and progress in the development of asymmetric Heck reactions (AHR) [68], This methodology allows for the preparation of enantiomerically enriched products from achiral substrates using a catalytic amount of a chiral palladium complex, making the process practical and economical. For example, treatment of triflate 71 with catalytic Pd(OAc)2/(R)-BlNAP provided oxindole 72 in 96% yield and 88% ee [69]. 

The intramolecular asymmetric Heck reaction has featured in the synthesis of complex heterocyclic compounds. Bidentate ligands, such as diphosphines (especially BINAP) and phosphine—oxazolines, have been used as a chiral ligand of the asymmetric Heck reaction. Imbos et al. demonstrated that the mono-dentate phosphoramidite 513 was an effective ligand for the asymmetric Heck reaction of the prochiral cyclohexadienone 511 (Scheme 153).227 The reaction of 511 in the presence of catalytic amounts of Pd-(OAc)2 and the chiral phosphoramidite 513 gave the 4a-methoxy-4a//-benzo[c]chromen-2(6E/)-one 512 in 71% yield with 96% ee. By contrast, the reaction of... 

The palladium catalyzed arylation of 1,3-dioxin has been used in the preparation of 4-aryldioxins (42). The use of these compounds as )S-formylvinyl synthons means that access to aryl derivatives, inaccessible by lithiation and alkylation, is possible (Scheme 15). Use of the asymmetric Heck reaction allowed the synthesis of optically active dioxin derivatives, albeit in modest enantiomeric excess <92TL6845). 

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