Chiral Pd-complex

An asymmetric variant of this reaction was developed using chiral Pd complex 111 with either silanes or disiloxanes [66-68]. Both relative and absolute stereochemistries were controlled in this system and good yields (60-85%) were obtained after oxidation (Eq. 18). Formation of the silane-containing product was inhibited by the presence of water due to competitive formation of the palladium hydrides and silanols [68]. The use of disiloxanes as reductants, however, provided expedient oxidation to the alcohol products without decreasing the isolated yields enantioselectivity was 5-15% lower in this more robust system [66]. Benzhydryldimethylsilane proved to be a good compromise between high yield and facile oxidation [66]. Palladium com-... 

Figure 4 Chiral Pd complexes (a) PdBr(p-CNC6H4)( S -MeO-Biphep) (b) PdBr(C6F5)( S -MeO-Biphep). Potential aromatic 7r-7r stacking interactions are indicated by arrows.

Unlike CO, it is possible to polymerize isocyanides (R—N=C), isoelectronic analogs to CO. When R is a bulky group, such as tert-Bu, the polymer forms a stable helical structure. Asymmetric catalytic polymerization has been reported for t-Bu-NC using [Ni(T 3-allyl)(iV-trifluoroacetyl-proline)]2 providing (M)-helical polymer with 69% ee. The more stable helical polymer was prepared from 1,2-diisocya-nobenzene derivative initiated by a chiral Pd complex. (See Scheme 4.19.)... 

Bicyclic hydrazines have also been ring-opened using 7t-allyl chemistry. Treatment of meio-bicyclic hydrazine 88 with a chiral Pd complex in the presence of phenol provides the allyl phenyl ether 89 in good yield and moderate enantios-electivity ... 

Asymmetric hydroalkoxycarbonylation of a-methylstyrene is also examined, leading to 3-phenyl-butanoic acid, the //< r///< /-product. The highest ee is at best 60% for this substrate.When an allylic alcohol is treated with a chiral Pd complex under GO, cyclohydrocarbonylation takes place to give the corresponding 7-butyrolactone in an asymmetric manner (Equation (6)). Similarly, chiral -lactones and other lactams can also be synthesized. 

A novel system for the enantioconvergent decarboxylative protonation of racemic /3-kclo esters has been developed.48 The reaction tolerates a variety of substitution and functionality and delivers products of high enantiopurity in excellent yield. The enan-tioinduction in the observed protonated products is consistent with the intermediacy of an enolate that is intimately associated with a chiral Pd complex. 

Catalytic enantioselective fluorination using chiral Pd complexes (59) and (60) has been reported.166,167 This method has provided various fluorinated compounds, includ- ing /3-keto phosphonates, oxindoles, and phenylacetate derivatives, in a highly enantioselective manner (75-96% ee). 

A very useful extension of the de Mayo reaction has been recently introduced by Blechert et al. (Scheme 6.26) [78]. The retro-aldol fragmentation was combined with an intramolecular enantioselective allylation (asymmetric ring-expanding allylation) catalyzed by a chiral Pd complex. Bicycloheptane 68, for example, was accessible by intermolecular [2 + 2]-photocycloaddition of cyclopentenone 67 with allene. Further transformation in the presence of Pd2(dba)3 (dba = dibenzylideneacetone) and the chiral oxazoline ligand 69 (tBu-phox) resulted in the enantioselective formation of cycloheptadione 70. 

Scheme 22. Asymmetric metallo-ene cyclization catalyzed by chiral Pd complex...

Development of novel catalytic asymmetric reactions mediated by chiral Pd complexes as acid-base catalysts and their application to synthesis of drug candidates 06CPB1351. 

The reaction of secondary phosphine boranes 211 with anisyl iodide, catalyzed by chiral Pd complex with (S,S)-Chiraphos, proceeded with retention of absolute configuration at phosphorus [135]. Addition of Pd((S,S)-Chiraphos)(o-An) to enantioenriched secondary phosphine 211 in the presence of NaOSiMc3 led to the formation of complex 212, stable at ambient temperature. This complex at +50°C in excess of diphenylacetylene allowed the formation of (/ p)-213 in yield of 70% and with enantiomeric purity of 98% ee (Scheme 68). 

This asymmetric transformation includes neither racemization nor epimerization. Both enantiomeric substrates, S, and Sj, are converted to a single enantiomeric intermediate I having two diastereotopic reaction sites through the interaction with a chiral catalyst or reagent. The selectivity is determined only by the rate ratio in the two reaction pathways to Pj and Pj, while the rate of formation of I from Sf, and Sj and their equilibrium affect only the overall rate of the reaction Scheme 5.54 shows a typical example [143]. A chiral Pd complex reacts with racemic 2-cyclohexenyl acetate to form a chiral tr-allyl intermediate, in which the stereogeruc centre of the substrate is lost The reaction with a lithium salt of dimethyl malonate gives the alkylated malonate in 91% yield and 98% ee. 

In cases where either addition or substitution proceeding via double bond migration is involved, one or more asymmetric carbon centers may be generated. Thus, face selective TT-complexation with chiral Pd complexes can, in principle, lead to asymmetric processes [15],[16] (Sect, V.3.1.1), although this possibility has not yet been extensively investigated. 

The use of chiral Pd complexes for asymmetric synthesis is another clear-cut case requiring specially designed ligands. For the asymmetric Heck reaction, both (a) mixtures of conventional Pd complexes, such as Pd(OAc)2 and Pd2dba3, and chiral ligands, such as BINAP, and (b) preformed chiral Pd complexes, such as Cl2Pd(BINAP), have been used. 

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