Catalyzed ligand substitution reactions

It may be concluded from die different examples sliown here tiiat die enantio-selective copper-catalyzed allylic substitution reaction needs ftirdier improvemetiL High enantioselectivities can be obtained if diirality is present in tiie leaving group of die substrate, but widi external diiral ligands, enantioselectivities in excess of 9096 ee have only been obtained in one system, limited to die introduction of die sterically hindered neopeatyl group. 

Complexes derived from the oxazolinylpyridine ligand Ph-Pybox and [Ir(COD)Cl]2 catalyze allylic substitution reactions of several oxygen and nitrogen nucleophiles... 

Except for one recent example, all iridium-catalyzed allylic substitution reactions have been performed under an inert atmosphere with dry solvent and reagents. The iridium metalacycle is sensitive to protonation, which opens the metalacycle and results in the formation of a less-active complex containing a K -phosphoramidite ligand. A paper by Helmchen et al. addressed this issue [107]. Nearly all iridium catalysts used for allylic substitution consist of an iridium fragment chelated by COD. In the presence of a catalyst containing dibenzo[a,c]cyclooctatetraene (dbcot) in place of COD, allylic substimtion reactions occur in air with results that are comparable to those of reactions performed under an inert atmosphere (Scheme 35). 

Figure 1.10 Ligands and allylic substrates for Ir-catalyzed allylic substitution reactions.

Scheme 6. Parallel screening of ligand libraries indicates that pyridyl dipeptides can serve as effective ligands for Cu-catalyzed allylic substitution reactions that afford quaternary carbon centers enantioselectively...

Amino acids can be accessed by a palladium-catalyzed allylic substitution reaction (Scheme 22.19).145 Some ligand screening is necessary to obtain high selectivity in a specific case. Indeed, a wide range of ligands has been proposed for this and analogous reactions.145 143... 

From a practical standpoint, it is of interest to devise a one-step synthesis of the catalyst. Since both reactions 2 and 3 are ligand substitution reactions, it is quite conceivable that both steps can be carried out at the same time. When we reacted [Ru(COD)Cl2]n with BINAP and sodium acetate in acetic acid, we indeed obtained Ru(BINAP)(OAc)2 in good yields (70-80%). Interestingly, when the reaction was carried out in the absence of sodium acetate, no Ru(BINAP)(OAe)2 was obtained. The product was a mixture of chloro-ruthenium-BINAP complexes. A 3ip NMR study revealed that the mixture contained a major species (3) (31P [ H] (CDCI3) Pi=70.9 ppm P2=58.3 ppm J = 52.5 Hz) which accounted for more than 50% of the ruthenium-phosphine complexes (Figure 2). These complexes appeared to be different from previously characterized and published Ru(BINAP) species (12,13). More interestingly, these mixed complexes were found to catalyze the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid with excellent rates and enantioselectivities. 

Though largely unstudied, it has recently been shown that Ir-catalyzed allylic substitution reactions where a strong n-acceptor ligand, for example, triphenylphosphite, is present... 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

An S—P-type chiral phosphinooxathiane was developed as an effective ligand for palladium-catalyzed allylic substitution reactions [131]. A polymer-supported chiral phosphinooxathiane 208 was also prepared and applied to asymmetric alkylations and aminations of acetate 201 [132]. Enanhoselechvihes of up to 99% ee were obtained in asymmetric Pd-catalyzed allylic amination of acetate 201 using the polymeric catalyst prepared from a PS-diethylsilyl support (Scheme 3.68). 

Allylic ethers and alcohols have long been known to react with Grignard reagents in the presence of an appropriate Ni-based complex containing phosphine ligands [26]. These reactions are related to the well-studied Pd-catalyzed allylic substitution reactions that utilize soft nucleophiles [27], and a number of important mechanistic studies on the stereochemical outcome of this class of transformations have been carried out [28]. 

Activated methylene compounds such as dimethyl malonate have found substantial utility in palladium catalyzed allylic substitution reactions. Accordingly, the Krapcho decarboxylation is often used in conjunction with these reactions. As an example, the first total synthesis of enantiomerically pure (-)-wine lactone has utilized the sequence of reactions.27 First, the allylic substitution reaction of 2-cyclohexen-l-yl acetate (49) with alkali sodium dimethylmalonate yielded 51 with high enantioselectivity, as a result of the use of chiral phosphine ligand 50. The malonate was then subjected to Krapcho decarbomethoxylation using NaCl, H2O, and DMSO at 160 °C to yield 52. This reaction has been used similarly following the allylic substitution reaction with other malonate derivatives.28-30... 

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