Asymmetric palladium

Trost and co-workers have explored asymmetric transidon metal-catalyzed allylic alkyla-dons. Details on this subject have been well reviewed by Trost and others. With the use of asymmetric palladium-catalyzed desymmetrizadon of meso-2-ene-l,4-diols, cii -l,4-dibenzoy-loxy-2-cyclopentene can be converted to the enandometrically pure cii -4-rfirr-butoxycar-bamoyl-l-methoxycarbonyl-2-cyclopentene. The product is a usefid and general building block for synthesis of carbocyclic analogs of nucleosides as presented in Scheme 5.12. 

In an extension of this work, the Shibasaki group developed the novel transformation 48—>51 shown in Scheme 10.25c To rationalize this interesting structural change, it was proposed that oxidative addition of the vinyl triflate moiety in 48 to an asymmetric palladium ) catalyst generated under the indicated conditions affords the 16-electron Pd+ complex 49. Since the weakly bound triflate ligand can easily dissociate from the metal center, a silver salt is not needed. Insertion of the coordinated alkene into the vinyl C-Pd bond then affords a transitory 7t-allylpalladium complex 50 which is captured in a regio- and stereocontrolled fashion by acetate ion to give the optically active bicyclic diene 51 in 80% ee (89% yield). This catalytic asymmetric synthesis by a Heck cyclization/ anion capture process is the first of its kind. 

In addition, various chiral (p-A -sulfonylaminoalkyl)phosphine ligands were earlier employed by Achiwa et al. for the asymmetric palladium-catalysed hydrosilylations of cyclopentadiene and styrene, affording the corresponding... 

Equation 11.37 Asymmetric palladium-catalyzed allylic alkylation (BSA = N,0-bis(trimethylsilyl)acetamide). 

Used in Asymmetric Palladium-Catalyzed Allylic Alkylations 320... 

Structural Identification of a Palladium Complex with a Chiral Sulfoxide Ligand Used in Asymmetric Palladium-Catalyzed Allylic Alkylations... 

Asymmetric Palladium-catalyzed Allylic Alkylation of Allylic Alcohols... 

In sharp contrast to a fully developed asymmetric palladium-catalyzed allylic substitution as described in the previous sections of this chapter, similar reactions using transition metal complexes other than palladium have not yet been fully investigated and their application to organic synthesis is quite limited at the present. In this section, examples of Cu-, Ni-, Pt-, Rh-, Ir-, Ru-, Mo-, and W-catalyzed allylic alkylation are summarized including recent developments in this field. 

Hallberg and his co-workers reported in 1999 the first microwave-promoted asymmetric palladium-catalyzed allylic alkylation of acyclic and cyclic allylic esters with dimethyl malonate, using some chiral ligands 57 and 118 (Equations (65) and (55))3 s,l6Sa,i6Sb both cases, microwave irradiation reduces reaction time without any loss of enantio-selectivity. The same group successfully applied this reaction system to the molybdenum-catalyzed allylic alkylation (Equation ((,7)) 60.160 -l60. 

An approach to the related natural product, (-t-)-xestoquinone (11.3), has been reported by Keay and co-workers in which an asymmetric palladium-catalyzed polyene cyclization is used... 

Kaneko, S. Yoshino, T. Katoh, T. Terashima, S. A novel enantioselective synthesis of the key intermediate of (—)-huperzine A employing asymmetric palladium-catalyzed bicycloannulation. Tetrahedron-Asymmetry, 1997, 8(6) 829-832. 

Trost has reported enhanced enantioselectivity in the desymmetrization of mero-biscarbamates in the presence of triethylamine. Under these conditions, high yields (>80%) and enantiomeric excesses (93-99% ee) are obtained. This methodology has been applied to the synthesis of (—)-swainsonine. a-Amino esters have been used as nucleophiles in the reaction with acyclic allylic esters and isoprene monoepoxide, providing access to diastereoselective N-alkylated a-amino esters. By employing the feature ligand, asymmetric palladium(0)-catalyzed cychzation of 2-(tosylamino)phenol with ( -l,4-bis[(methoxycarbonyl)oxy]but-2-ene provides 2-vinylbenzomorpholine in 79% ee. A number of alternative diphosphine ligands were studied and found to be inferior. 

The stereoselective allylation of aldehydes was reported to proceed with allyltrifluorosilanes in the presence of (S)-proline. The reaction involves pentacoordinate silicate intermediates. Optical yields up to 30% are achieved in the copper-catalyzed ally lie ace-toxylation of cyclohexene with (S)-proline as a chiral ligand. The intramolecular asymmetric palladium-catalyzed allylation of aldehydes, including allylating functionality in the molecules, via chiral enamines prepared from (5)-proline esters has been reported (eq 15). The most promising result was reached with the (S)-proline allyl ester derivative (36). Upon treatment with Tetrakis(triphenylphosphine)palladium(0) and PPh3 in THF, the chiral enamine (36) undergoes an intramolecular allylation to afford an a-allyl hemiacetal (37). After an oxidation step the optically active lactones (38) with up to 84% ee were isolated in high chemical yields. The same authors have also reported sucessful palladium-catalyzed asymmetric allylations of chiral allylic (S)-proline ester enamines" and amides with enantiomeric excesses up to 100%. 

In a recent study, a significant improvement was accomplished in the asymmetric palladium-catalyzed 1,4-hydrosilylation of cyclic 1,3-dienes with the use of chiral ligand (/ )-MOP-phen (Scheme 8-2) [18]. Thus hydrosilylation of cyclopentadiene gave 5 in 99% yield with an enantiomeric excess of 80%, which is the highest reported ee value for Pd-catalyzed hydrosilylations of 1,3-dienes. With 1,3-cyclohexadiene, the yield of the... 

Stephenson, G. R. Asymmetric palladium-catalyzed coupling reactions (ed. Stephenson, G. R.) (Chapman Hall, London, 1996) 275-298. 

Miyaura, N., Suzuki, A. Paiiadium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457-2483. Stephenson, G. R. Asymmetric palladium-catalyzed coupling reactions (ed. Stephenson, G. R.) (Chapman Hall, London, 1996) 275-298. Browning, A. F., Greeves, N. Palladium-catalyzed carbon-carbon bond formation (eds. Beller, M.,Bolm, C.) (Wiley-VCH, Weinheim, New York, 1997) 35-64. 

The coordination chemistry of many chiral ligands is directed towards preparing complexes with catalytically useful metals, most notably late transition metals. Some Rh, Pd, Pt, and Ag complexes of Diop (149) (and also (150)) have been described,327,328,381,382 along with the use of palladium Diop complexes in asymmetric palladium catalysed cross-couplings383 and alkene hydrocyanation reactions. 

Subsequently, better ligands than 44 have been designed for the asymmetric palladium-catalyzed reaction of 1,3-diphenylallyl acetate with sodium mal-onate. Both the bis-(phosphaferrocene) 48 synthesized as shown in Eq. (32) [77] and the phosphaferrocene-oxazolines 49 [78] perform this condensation with much higher ees (79% in the first case and up to 82% in the second case). In the second case, the stereochemical outcome of the reaction is determined by the planar chirality at the phosphaferrocene, rather than the chirality of the oxazo-line [78] ... 

FIGURE 13.15. Microwave acceleration of an asymmetric palladium-catalyzed alkylation... 

The effects of temperature and cathode material and the use of aluminium electrodes on the electrolysis of phosphonium salts have been studied. Miscellaneous. Patent specifications have appeared for the convenient resolution of tertiary phosphines by complexation with the asymmetric palladium(n) complex (20). 

DIYL)BIS[(4S)-4-PHENYL-2-OXAZOLINE] AS A LIGAND FOR ASYMMETRIC PALLADIUM-CATALYSED ALKYLATION OF ALLYLIC ACETATES IN FLUOROUS MEDIA... 

Asymmetric palladium(0)-catalysed substitution of racemic allylic substrates with malonate and benzylamine as nucleophiles were performed using new enantiopure cyclic (3-iminophosphine ligands namely (2,6-dimethyl-phenyl)-( 1 -phenyl-2, 3,3a, 8a-tetrahydro- 1H-1 -phospha-cyclopenta[-a]inden-8-ylidene)-amines 1 (RP)... 

In summary, a new simple method for the preparation of axially chiral diphosphine complexes has been developed. The presence of the planar chiral ferrocenyl unit avoids the need of resolution since only one diastereomer is formed in a metal complexation. The new ligand is useful for asymmetric palladium-catalysed allylic substitutions with malonates and amino derivatives (Schemes 1 and 2). 

Early investigations on the asymmetric palladium(0)-catalyzed allylation of prostereogenic nucleophiles with allyl phenolates and acetates as electrophiles achieved up to 10% ee using Diop [4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-l,3-dioxolane] as the chiral ligand6. Other ligands like Prophos [1,3-bis(diphenylphosphino)propane]7 and sparteine8 also provided only poor stereoselectivities. 

Tertiary phosphines have been partially resolved by complexation with the asymmetric palladium(ii) complex (16), Treatment of this complex with racemic phosphine gave (17), phosphine of low rotation being recovered from the mother liquor. The enantiomeric phosphine can be... 

Phosphorous-containing amidine was prepared through several steps from L-valine and evaluated as a new ligand for asymmetric palladium (Pd) catalysed allylic alkylation of 1,3-diphenylprop-2-enyl acetate and pivalate [73]. The results with the nucleophile derived from dimethyl malonate are summarized in Table 3.5 [73a]. Excellent asymmetric inductions up to 95% ee were achieved along with an efficient conversion. 

Proton Sponge (1) sometimes drastically affects the enantiomeric excess and yield in the asymmetric palladium catalysed Heck reaction. 

Asymmetric palladium-catalyzed alkylation of various allylic acetates occurred in water or in an aqueous/organic biphasic medium, using as ligands phosphines derived from carbohydrates [29], amphiphilic resin-supported MOP and P,N-chelating ligands [30, 31], or BINAP in the presence of surfactants [32] enantio-selectivities up to 85%, 98%, and 92% have been obtained in the alkylation of 1,3-diphenyl-2-propenyl acetate, respectively. 

Scheme 20.13 Ligands for use in Trost asymmetric palladium-catalysis technology.

With their efficient procedure for deracemization of MBH adducts, Trost and coworkers have applied dynamic asymmetric kinetic transformation (DYKAT) to the total synthesis of furaquinodn E. As shown in Scheme 5.28, the asymmetric palladium-catalyzed alkylation of phenols combined with a reductive Heck reaction delivered an effident approach to the synthesis of the key synthon, which is the core structure of the furaquinocins. A general synthetic route to furaquinocin E was established in 14 steps from MBH adduct 159. Their work highlighted the ability to use racemic MBH adducts for asymmetric synthesis. They further extended the scope of their strategy by developing the synthesis of three more analogs of... 

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