BINAP enantioselective 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. 

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

The Shibasaki cychzation of mc.vo-cyclohexa-1,4-dienes in the presence of a chiral palladium complex and silver carbonate in l-methyl-2-pyrrolidinone is probably the first example of an enantioselective Heck reaction (Scheme 10.34).60 The enantiomeric excess could be slightly improved by replacing the chiral phosphine ligand BINAP with the corresponding less coordinating arsine ligand, as well as replacing silver carbonate with silver phosphate.61,62... 

These and other enantioselective Heck reactions were performed with a variety of chiral ligands (Table 3-8 and Figure 3-1). However, high enantioselectivities could so far only be achieved with BINAP (accessible in both enantiomeric forms) or oxazoline ligands (preferably the bulky 208). The latter is easily obtained as the (S )-enantiomer. 

Binap 3.43 is also a good ligand for palladium complexes. Although 71-allyl palladium-binap complexes have met limited applications in asymmetric allylation of malonate like derivatives [872], binap-PdCl2 complexes induce enantioselective Heck reactions [902] and 1,4-disilylations of a-enones [903],... 

Shibasaki (Equation 19.36) and Overman first reported the enantioselective Heck reaction. A few substrate combinations react intermolecularly with high enantiose-lectivity (Equation 19.37),but most enantioselective Heck reactions used in S)mthetic applications have been conducted intramolecularly. The asymmetric Heck reaction in Equation 19.37 has begun to be a test-bed for new chiral ligands. Although most Heck reactions that occur with high enantioselectivity have been conducted with BINAP as ligand, a phosphinooxazoline ligand has been used successfully (vide infra). Overman has applied an intramolecular version of the Heck reaction to form oxindoles (Equation 19.38) in the synthesis of a variety of natural products. ... 

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. °... 

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-... 

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. 

Benzamido-cinnamic acid, 20, 38, 353 Benzofuran polymerization, 181 Benzoin condensation, 326 Benzomorphans, 37 Benzycinchoninium bromide, 334 Benzycinchoninium chloride, 334, 338 Bifiinctional catalysts, 328 Bifiinctional ketones, enantioselectivity, 66 BINAP allylation, 194 allylic alcohols, 46 axial chirality, 18 complex catalysts, 47 cyclic substrates, 115, 117 double hydrogenation, 72 Heck reaction, 191 hydrogen incorporation, 51 hydrogen shift, 100 hydrogenation, 18, 28, 57, 309 hydrosilylation, 126 inclusion complexes, oxides, 97 ligands, 19, 105 molecular structure, 50, 115 mono- and bis-complexes, 106 NMR spectra, 105 olefin isomerization, 96... 

Use of the allylsilanes as the alkene components in the Heck reaction is illustrated in the regioselective intramolecular cyclization of 120 (equation 98)180. In addition, a high enantioselectivity of 90 %ee is obtained when the chiral phosphine (S)-BINAP is employed. The propargylsilane analog undergoes a similar reaction181. 

The remarkable affinity of the silver ion for hahdes can be conveniently applied to accelerate the chiral palladium-catalyzed Heck reaction and other reactions. Enantioselectivity of these reactions is generally increased by addition of silver salts, and hence silver(I) compounds in combination with chiral ligands hold much promise as chiral Lewis acid catalysts for asymmetric synthesis. Employing the BINAP-silver(I) complex (8) as a chiral catalyst, the enantioselective aldol addition of tributyltin enolates (9) to aldehydes (10) has been developed." This catalyst is also effective in the promotion of enantioselective allylation, Mannich, ene, and hetero Diels-Alder reactions. 

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. 

Another example of a pronounced positive pressure effect on enantioselectivity was found by Hillers and Reiser [82] for the Heck reaction of 2,3-dihydrofuran (180) and phenylperfluorobutylsulfonate (phenylnonaflate) (181) in the presence of (R)-BINAP (cf. Chapter 7) Under normal pressure and at 60 °C an enantiomeric excess of 47 % ee for 183 was achieved when 1.0 GPa was applied, the enatio-selectivity for 183 was improved to 89 % ee under otherwise unchanged conditions. On the other hand the ratio of 182 to 183 was only 1 1.6 at high pressure and 182 was obtained with an enantiomeric excess of only 5 % ee. Apparently, a very effective kinetic resolution had taken place under high pressure. It should be noted that the use of new chiral ligands for the described Heck reaction of tetrahydrofuran now allows an enantioselectivity of 96 % ee with complete regiocontrol at atmospheric pressure [83]. 

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