BINAP, asymmetric Heck reaction

A short five-step synthesis of a bifuran, namely ( )-2,2 -bis(diphenylphosphino)-3,3 -binaphtho[2,l-I>]furan (BINAPFu) from naphthofuranone via a low-valent titanium-mediated dimerization was reported. The newly developed resolution procedure for phosphines was utilized to provide the optically active bidentate phosphine ligands (BINAPFu), which consistently outperforms BINAP in the asymmetric Heck reaction between 2,3-dihydrofuran and phenyl triflate . Another way in which a benzofuranone can be converted into benzo[7 ]furan is by treatment of the former with 1-BU2AIH at -78°C followed by an acidic work up <00TL5803>. 

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). 

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

For intermolecular asymmetric Heck reaction between aryl triflates and 2,3-dihydrofuran the hindered diphosphine 1 is superior to BINAP. Improved enantioselectivity is due to the bulky f-butyl substituents to create a more ideal chiral pocket in the metal complexes. 

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... 

Asymmetric Heck reaction.3 Treatment of the vinyl triflatc I with tclrabulylam-monium acetate (1.7 equiv.) and a catalytie amount of Pd(OAc) and (S)-BINAP in DMSO at 20° results in the fused bicyclic pentanoid 2 in 80% ee, formed by a Heck reaction followed by an anion capture process. This product can be converted into 3, an... 

In the presence of a chiral ligand, asymmetric Heck reactions can be carried out. The axially-chiral bisphosphine ligand (/ )- or (5)-BINAP promotes good to excellent levels of enantioselectivity in intramolecular Heck reactions. For example, insertion of palladium into the aryl iodide 214 followed by cyclization gave the indolinone 215 in high enantiomeric excess, used in a synthesis of physostigmine (1.215). ... 

Nakamura and co-workers synthesized a heavily fluorinated chiral BINAP, (R)-6,6 - bis(tris (1H, 1 H,2 H,2 H-perfluorooctyl) srlyl]-2,2 -bis (diphenylphosphino)-1,1 -binaphthyl ((R)- FJ3BINAP) (F content = 54%, partition coefficient benzene/FC-72 = 26 74, CH3CN/FC-72 = 2 98) and applied it to an asymmetric Heck reaction [12). The reaction between 2,3-dihydrofuran and 4-chlorophenyl triflate was carried out under the same conditions as those of original nonfluorous reaction by using FjjBlNAP in BTF or benzene to provide the corresponding product, 2-(4-chloro-phenyl)-2,3-dihydrofuran, in 59% chemical yield or in 90% ee and 92% ee, respectively (71% chemical yield and 91% ee in the original reaction in benzene [13]) [Eq. (3)]. 

The asymmetric Heck reaction is catalysed by enantiomerically pure palladium catalysts formed with chelatingbiphosphines, especially BINAP, and this has proved an effective method for the synthesis of sterically constrained carbon centres, including quaternary centres. This chapter concludes with a brief discussion of enantioselective alkylmetallations using Grignard and organoaluminium species, which have proved useful in the diastereo- and enantioselective synthesis of polyene systems. 

Dihydrofuran (10.137) has also proved to be a popular substrate for the asymmetric Heck reaction. Hayashi has reported that using a Pd/BINAP catalyst not only is the initial addition enantioselective, but that the diastereomeric intermediates, i.e. of structure (10.119) preferentially give different regioisomeric products (10.138) and (10.139). This effect is similar to that of a kinetic resolution (see Section 4.1). ... 

Compared to very extensive studies on Heck reactions, examples of successful asymmetric Heck reactions (abbreviated to AHR in this section) are rather limited, showing that AHRs are not easy to carry out, and careful tuning of conditions is crucial. Most of the HRs proceed by using monodentate ligands. On the other hand, chiral bidentate ligands are mainly required for AHRs. This may be a reason for the difficulty in achieving efficient AHRs. The ligands most extensively used are BINAP, its derivatives, and phosphinooxazolines [116]. 

The Pd((R)-binap)2 species, which was an active catalyst for asymmetric Heck reaction, was prepared. However, little is known about its characterization. Only the H and... 

With this step accomplished as desired, probes of the key step of the sequence, the tandem asymmetric Heck reaction, could now commence in earnest. Based on several years of intensive research in developing appropriate systems to accomplish asymmetric Heck reactions with the ability to form all-carbon quaternary carbon centers, the Overman group expected that the exposure of 10 to a 1 2 mixture of Pd(OAc)2 and (/ )-BINAP would lead to the desired... 

Nakamura, Y., Takeuchi, S., Zhang, S. et al. (2002) Preparation of a fluorous chiral BINAP and application to an asymmetric Heck reaction. Tetrahedron Lett., 43, 3053-6. 

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