Pd 2, BINAP

The reaction of a halide with 2-butene-1,4-diol (104) affords the aldehyde 105, which is converted into the 4-substituted 2-hydroxytetrahydrofuran 106, and oxidized to the 3-aryl-7-butyrolactone 107[94], Asymmetric arylation of the cyclic acetal 108 with phenyl triflate[95] using Pd-BINAP afforded 109, which was converted into the 3-phenyllactone 110 in 72% ee[96]. Addition of a molecular sieve (MS3A) shows a favorable effect on this arylation. The reaction of the 3-siloxycyclopentene 111 with an alkenyl iodide affords the. silyl... 

For the activation of a substrate such as 19a via coordination of the two carbonyl oxygen atoms to the metal, one should expect that a hard Lewis acid would be more suitable, since the carbonyl oxygens are hard Lewis bases. Nevertheless, Fu-rukawa et al. succeeded in applying the relative soft metal palladium as catalyst for the 1,3-dipolar cycloaddition reaction between 1 and 19a (Scheme 6.36) [79, 80]. They applied the dicationic Pd-BINAP 54 as the catalyst, and whereas this type of catalytic reactions is often carried out at rt or at 0°C, the reactions catalyzed by 54 required heating at 40 °C in order to proceed. In most cases mixtures of endo-21 and exo-21 were obtained, however, high enantioselectivity of up to 93% were obtained for reactions of some derivatives of 1. 

Concerning enantioselective processes, Fujihara and Tamura have proved that palladium NPs containing (S)-BINAP (2,2 -bis(diphenylphosphino)-l,l -binaphthyl) as chiral stabiliser, catalyse the hydrosilylation of styrene with trichlorosilane, obtaining (S)-l-phenylethanol as the major isomer (ee = 75%) [42]. In contrast, the palladium complex [Pd(BINAP)(C3H5)]Cl is inactive for the same reaction [43]. 

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). 

Scheme 26.2 Amination of aryl halides catalyzed by Pd(binap).

We can see from Figure 26.3 that a complex arises at the beginning, showing peaks in both the phosphoras and fluorine NMR it is the same previously observed during the benzophenone reaction when the hexylamine reaction starts, and its product begins to form, this complex disappears and a single peak in the P is visible, referring to the Pd(BINAP)2. 

The initial dominance of path b in the competitive reaction arises because the concentration ratio [6 )]/[4] is large enough to overwhelm the reactivity ratio j[rirX]/, which would favour the more reactive path a. This supports previous suggestions that the Pd(BINAP), which has never been isolated or observed spectroscopically, exists only fleetingly in stoichiometric and catalytic reaction networks. 

Singh, U., Strieter, E., Blackmond, D., and Buchwald, S. Mechanistic insights into the Pd(BINAP)-catalyzed amination of aryl bromides kinetic studies under synthetically relevant conditions. J. Am. Chem. Soc. 2002, 724, 14104-14114. 

Aldol reactions of silyl enolates are promoted by a catalytic amount of transition metals through transmetallation generating transition metal enolates. In 1995, Shibasaki and Sodeoka reported an enantioselective aldol reaction of enol silyl ethers to aldehydes using a Pd-BINAP complex in wet DMF. Later, this finding was extended to a catalytic enantioselective Mannich-type reaction to a-imino esters by Sodeoka s group [Eq. (13.21)]. Detailed mechanistic studies revealed that the binuclear p-hydroxo complex 34 is the active catalyst, and the reaction proceeds through a palladium enolate. The transmetallation step would be facilitated by the hydroxo ligand transfer onto the silicon atom of enol silyl ethers ... 

Furukawa and co-workers (368,369) succeeded in applying the softer dicationic Pd-BINAP 260 as a catalyst for the 1,3-dipolar cycloaddition between 225 and 241a (Scheme 12.82). In most cases, mixtures of endo-243 and exo-243 were obtained, however, enantioselectives of up to 93% ee were observed for reactions of some derivatives of 225. A transition state structure has been proposed to account for the high selectivities obtained for some of the substrates (368). In the structure shown in Scheme 12.82, the two phosphorous atoms of the Tol-BINAP ligand and the two carbonyl oxygens of the crotonoyl oxazolidinone are arranged in a square-planar fashion around the palladium center. This leaves the ii-face of the alkene available for the cycloaddition reaction, while the re-face is shielded by one of the Tol-BINAP tolyl groups. 

Zinc dibenzyl malonate complex 129, prepared by the action of Et2Zn on dibenzyl malonate, was found to be superior to alkali metal dibenzyl malonates, in terms of enantiomeric control, in the allylic substitution with ( )-130 catalysed by an in situ prepared Pd-(/ )-BINAP complex (equation 73)164. 

For this particular cis-decalin synthesis, it was eventually found that best results were obtained with the corresponding vinyl triflates and Pd(BINAP) (Scheme 8G.5) [l 3). As illustrated in these examples, the reaction of unsaturated triflates under cationic conditions typically is done in a nonpolar solvent, in the presence of an inorganic base such as K2C03 or a tertiary amine Pd(OAc)2 and Pd dba CHC have been the most widely used palladium sources. 

Their most detailed investigations focused on the Heck cyclization of iodide 18.1c to form oxindole 17.3a (Scheme 8G.18) [38a,b]. A chiral-amplification study [47] established that the catalytically active species is a monomeric Pd-BINAP complex, a conclusion also corroborated by NMR studies by Amatore and co-workers [42d,43], In addition, two possibilities for the enantioselective step of the neutral pathway were easily eliminated [38a], Oxidative addition was precluded as the enantioselective step, because iodides cyclize with very different enantioselectivities in the presence of Ag(I) salts. A scenario where migratory insertion is reversible and [l-hydridc elimination is the enantioselective step was also ruled out, because this is not consistent with the dependence of enantioselectivity on the geometry of the double bond of the cyclization precursor. 

Enones are also bis-silylated. Asymmetric 1,4-bis-silylation of the enone 505 catalyzed by Pd-BINAP afforded the silyl enol ether 507, and the keto alcohol 509 with 87% ee was obtained after hydrolysis and oxidation of 508 [195]. In this case, the unsymmetric disilane 506 should be used. 

Treatment of a benzene solution of Pd(OAc)2 and 3 equivalents of (/ )-BINAP with an excess amount of Et3N resulted in change in the color of the solution from yellow to red. 31P lYL] NMR study of the resulting solution revealed the formation of [Pd (/ )-BINAP 2] and (/ )-BINAP monoxide ((fl)-BINAP(O)) in a 1 1 ratio. Labeling experiments showed the participation of 1 equivalent of residual water in the reduction system. Thus, the reaction carried out in solution saturated with 18OH2 gave lsO-labeled (fl)-BINAP(l80). 

Some optically active 3-alkoxycarbonyl-2-methylisoxazolidines were obtained by asymmetric decomposition in the presence of catalytic amount of Pd-BINAP complex. For instance, the kinetic resolution of racemic 105 by 106 afforded (+)-105 in 48% yield and with... 

The quadrant model which has been described for [Ru-BINAP] can normally be applied analogously with [Pd-BINAP] [15] and [Rh-BINAP] complexes. A new example for the latter is the hydroacylation of 4-substituted 4-pentenal 27 to 3-substituted cyclopentenones 28 using the [Rh-BINAP]C104 catalyst (Scheme 6). However, the strong dependence of the selectivity upon the nature of the substituents R suggests that stereoelectronic factors have to be taken into account as well [16]. 

Similarly, Lemi re utilized the Pd/BINAP-protocol to prepare the amino-flavone below in 50% yield over two steps from the corresponding triflate, Eq.(133) [113]. 

The asymmetric Heck cyclization of 5.15 takes place with high enantioselectivity (71-98%) with the Pd-BINAP catalyst to form the corresponding 3-alkyl-3-aryloxindole ° 5.16. A wide variety of aryl and heteroaryl substituents can be introduced into an oxindole by this method. This asymmetric synthesis of 3-aryl- or 3-heteroaryl oxindoles is very useful for the enantioselective synthesis of a range of indole alkaloids k... 

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