BINAP ligand formation

An unusual feature of this complex was that one of the phosphorus-naphthyl bonds in the BINAP ligand was ruptured. Based on the mechanisms elucidated for die P-C bond cleavage on Rh-phosphine complexes (14), we speculated a possible path for the formation of 3 via oxidative addition of the phosphorus-naphthyl bond to the Ru center (Figure 3). 

Asymmetric hydrogen transfer from EtOH, /-PrOH or triethylammonium formate to Z-a-acetamidocinnamic acid Z-3.32 (R = Ph, Z = COMe, R = H) or to itaconic acid 7.7 (R = H) is highly enantioselective when the catalyst is a binap-Ru complex [873, 1333] (Figure 7.14). The relationship between the absolute configuration of the saturated add and the binap ligand is the same as in the catalytic hydrogenation. However, hydrogen transfer to other a,P-unsaturated acids, such as the precursor of naproxen (7.15), is less enantioselective [1333],... 

Chiral morpholines and piperazines. The ring formation by tandem allylic substitutions of l,4-diacetoxy-2-butene with 1,2-amino alcohols and 1,2-diamines is promoted by Pd(0) complexes. In the presence of a chiral BINAP ligand this reaction gives optically active products. 

The normal neutral pathway (22 24 25 27) was ruled out by conducting the reaction with monodentate phosphine BINAP ligand mimics (Scheme 12.5). The products obtained were of low enantiomeric excess relative to reactions employing BINAP. The direct cationic pathway (24-> 26) was also eliminated due to the fact that the opposite stereochemistry was obtained under cationic conditions with the addition of silver salts. The switch in stereoselectivity in the presence of silver salts, moreover, indicates that oxidative insertion is not the enantioselective step. j8-Hydride elimination was also discounted as the enantioselective step due to the influence of the double-bond geometry of the starting material on the enantioselectivity of the cyclization. The proposed enantioselective step is the formation of the cationic intermediate 26 by an associative displacement (24-> 28-> 26). In the case of square planar pafladium(n) complexes, substitution chemistry can occur through associative processes. Axial coordination of the alkene would form the pentacoordinate pafladium(II) complex 28. Reports of isolated and characterized pentacoordinate palladium(II) species provide support for this proposed intermediate. 

Several studies were performed in order to establish the mechaiusm (5-7). The currently accepted mechartism, presented in Scheme 26.1 for the Pd(BINAP) catalyzed amination, involves the formation of a complex, Pd(BINAP)2 from a catalyst precursor (usually Pd(OAc)2 or Pd2(dba)3) and ligand this complex lies outside the catalytic cycle and undertakes dissociation of one BINAP to form Pd(BINAP) the following steps are the oxidative addition of the aryl halide to the Pd(BINAP), reaction with amine and base, and the reductive elimination of the product to reform Pd(BlNAP). 

A palladium-catalyzed protocol for carbon-sulfur bond formation between an aryl triflate and para-methoxybenzylthiol was introduced by Macmillan and Anderson (Scheme 6.66) [138], Using palladium(II) acetate as a palladium source and 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) as a ligand, microwave heating of the two starting materials in N,N-dimethylformamide at 150 °C for 20 min in the presence of triethylamine base led to the formation of the desired sulfide in 85% yield. 

Due to the potential problems associated with f3-H elimination, the first examples that were reported involved the intramolecular formation of G-O bonds between tertiary alcohols and aryl bromides using Pd(OAc)2 with 2,2 -bis(di-/>-tolylphosphino)-l,l -binapthyl (tol-BINAP) or bis(diphenylphosphino)ferrocene (dppf) as the ligands (Equation (12)).91 Although the coupling with primary and secondary alcohols was troublesome with this system, the more recent introduction of ligands 23-28 (Figure 3) has ameliorated many of these difficulties (Equation (13)).92... 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

Chirality transfer in catalytic asymmetric hydrogenation can be achieved not only by using powerful chiral ligands such as BINAP or DuPhos but also by the formation of a dynamic conformational isomer. The availability of many enantiomerically pure diols allows the production of electron-deficient, bi-dentate phosphate in the form of 27. The backbone O-R -O can define the chirality of the 0-R2-0 in complex 28, hence realizing the chirality transfer.44... 

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