Heck reaction enantioselectivity

Enantioselective Hydroarylation/Hydroalkenylation of Alkene C=C Bonds (Heck Reaction). Enantioselective in-... 

Use of Qi-acetamidoacrylate esters in the Heck reaction allows for the introduction of a dehydroalanine side-chain. The dehydrotryptophans can be reduced catalytically, and this reduction can be done enantioselectively[17]. 

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

Larhed et al. investigated enantioselective Heck reactions with 2,3-dihydrofuran as alkene [86]. In the coupling with phenyl triflate, conditions previously reported by Pfaltz [87] were attempted under microwave irradiation. Interestingly, the catalytic system Pd2(dba)3/(4S)-4-t-butyl-2-[2-(diphenylphosphanyl)phenyl]-4,5-dihydro-l,3-oxazole, identified by the Swiss team, was found suitable for high-temperature microwave-assisted enantioselective Heck reactions (Scheme 76). Using a proton sponge as a base and benzene as a solvent gave the best conversions (Scheme 76). At tempera-... 

Although sulfur is unHkely to chelate the metal in this case, it is worth mentioning the axially chiral diphosphine Hgands, based on hz-thienyl systems which increase the electronic density at phosphorus such as 159 (used in Ru-catalyzed reduction of /1-keto esters with 99% ee) [llla],BITIANP 160,andTMBTP 161 (in a Pd-catalyzed Heck reaction, the regio- and enantioselectivity are high with 160 but low with 161) [mb]. 

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

The Shibasaki group [27] developed an enantioselective total synthesis of (+)-xes-toquinone (6/1-38) using an asymmetric double Heck reaction with BINAP as chi-... 

Scheme 6/1.17. Influence of the substitution pattern on the enantioselectivity in intramolecular double Heck reaction.

Shibasaki and coworkers [87] described the first enantioselective combination of this type in their synthesis of halenaquinone (6/1-162) (Scheme 6/1.43). The key step is an intermolecular Suzuki reaction of 6/1-159 and 6/1-160, followed by an enantioselective Heck reaction in the presence of (S)-BINAP to give 6/1-161. The ee-value was good, but the yield was low. 

The most important reaction based on Pdn-catalysis is the Wacker oxidation [171], which is used industrially for the synthesis of acetaldehyde, starting from ethane. This process can be combined with a Heck reaction and has been used by Tietze and coworkers [172] for an efficient enantioselective synthesis of vitamin E (6/1-... 

Other enantioselective reactions performed by microwave heating include asymmetric Heck reactions (Scheme 6.53 a) [109] and ruthenium-catalyzed asymmetric hydrogen-transfer processes (Scheme 6.53 b) [110]. 

Novel C2-symmetric thiophene-containing ligands have recently been prepared and utilized in asymmetric synthesis. Dithiophene 158 was utilized as a ligand in the asymmetric reduction of p-ketoesters (prostereogenic carbonyl) and acrylic acids (carbon-carbon double bond) <00JOC2043>. Dibenzo[b]thiophene 159 was utilized as a ligand in enantioselective Heck reactions of 2-pyrrolines <00SL1470>. 

Phosphino-imidazoline ligands of this type were originally synthesized by Bu-sacca and coworkers and used in an enantioselective Heck reaction [28]. 

In these Heck reactions some degree of enantioselectivity (up to 83% ee) is achieved in the presence of (/ )-BINAP, although the yields of Heck products are often very low in the highest degree of enantioselectivity (e.g., 19% isolated yield at 83% ee) [93]. An example of a tandem Heck reaction is shown below involving the arylation of dihydropyrrole 132 with 1-naphthyl triflate (133) [92]. Complete chirality transfer is observed for the arylation of 134 to 135. 

Scheme 16. Results from the enantioselective Heck reaction using BINAP and PHOX.

O. Loiseleur, M. Hayashi, M. Keenan, N. Schmees, A. Pfaltz, Enantioselective Heck Reactions using Chiral PN-Ligands, J. Organomet. Chem. 1999, 576,16-22. 

Intermolecular, enantioselective Heck reactions require a cyclic olefin as substrate, since syn carbopal-ladation of a cyclic olefin results in a geometrically defined a-alkyl-palladium compound. By necessity, the subsequent syn dehydropalladation must take place away from the newly formed chiral centre, thereby affording a chiral product. 

Regio- and enantioselective Heck reactions of 2 3-dihydrofuran with aryl and alkenyl triflates in the presence of the chiral ligand (R)-BITIANP provides 2-substituted 23-dihydro-furans with complete regioselectivity, high enantioselectivity (86-96% ee) and good yields (76-93%) <99CC1811>. A catalytic oxyselenylation-deselenylation reaction of alkenes offers a stereoselective one-pot conversion of alkenes into 2 -dihydrofurans <99EF0797>. 

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