Enantioselective reactions allylic substitutions

The configuration of the chiral BlNOLate backbone of the phosphoramidite ligand affects the rates and enantioselectivities of allylic substitution reactions. Hartwig and coworkers found that allylic substitution conducted with a catalyst derived from the simplified ligand (5a,/ )-L4 occurred more slowly than that conducted with a catalyst derived from (/ a,/ )-L4 [74]. Complexes of the mismatched (5a,/ )-L4 undergo cyclometalation slowly. The products formed from reactions catalyzed by complexes of (5a,/ )-L4 and (/ a,/ )-L4 have the opposite absolute configuration. 

Abstract Chiral ferrocenyl phosphine ligands are certainly one of the most developed and successful classes of chiral ligands used in asymmetric catalysis. The literature describing their synthetic and coordination chemistry, as well as their metal-mediated applications in the field of catalysis, is extremely rich and varied. Moreover, they represent a rare example in which enantioselective chemical catalysts were used in industrial processes. The present chapter provides an account of the planar-chiral ferrocene ligands developed in the Authors laboratory, including their coordination chemistry with various metals as well as their use in different asymmetric catalytic reactions (allylic substitution, Suzuki coupling, methoxycarbonylation of alkenes, hydrogenation of ketones). 

Although the limited examples of AE reactions on 2,3Z-substituted allyl alcohols appear to give product epoxides in good enantioselectivity, the highly substituted nature of these olefins can have a deleterious effect on the reactivity. For example, Aiai has shown that the 2,3E-substituted allyl alcohol 30 can be epoxidized with either (-)-DET or (+)-DET in good yields and enantioselectivity. However, the configurational isomer 32 is completely unreactive using (-)-DET, even after a 34 h reaction time. 

S ]2 -selective reactions between primary allylic substrates and otganocoppet reagents testiU in the creation of new Chirality in previously aChital molecules, and it is tempting to try to take advantage of this for the development of enantioselective allylic 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. 

Since Pd complexes are well-known catalysts for enantioselective allylic substitution reactions, here the catalytic behaviour of palladium NPs for this reaction is examined (Scheme 1). One example involving a chiral phosphite with a carbohydrate backbone, able to coordinate firmly at the surface of NPs together with oxygen atoms capable to interact weakly with this surface, is presented. In particular. 

Since carbohydrates constitute an inexpensive and highly modular chiral source for preparing chiral ligands," Claver et al. have reported the use of a series of thioether-phosphite" and thioether-phosphinite furanoside ligands" in the test palladium-catalysed allylic substitution reaction. In the first type of ligand, a systematic variation of the donor group attached to the carbon atom C5 indicated that the presence of a bulky phosphite functionality had a positive effect on the enantioselectivity. Indeed, the enantioselectivity was controlled mainly by the phosphite moiety. This was confirmed by the use of a ligand... 

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

The first enantioselective, iridium-catalyzed allylic substitution was reported by Helmchen and coworkers soon after the initial report by Takeuchi. Helmchen studied catalysts generated from phosphinooxazoline (PHOX) ligands and [Ir(COD)Cl]2 for the reactions of sodium dimethylmalonate with cinnamyl acetates (Scheme 2) [50]. The alkylation products were isolated in nearly quantitative yield and were formed with ratios of branched-to-Unear products up to 99 1 and with enantioselectivities up to 95% ee. In this and subsequent studies with PHOX ligands [51,52], Helmchen et al. demonstrated that the highest yields and selectivities were obtained with a PHOX ligand containing electron-withdrawing substituents and... 

As previously discussed, activation of the iridium-phosphoramidite catalyst before addition of the reagents allows less basic nitrogen nucleophiles to be used in iridium-catalyzed allylic substitution reactions [70, 88]. Arylamines, which do not react with allylic carbonates in the presence of the combination of LI and [Ir(COD)Cl]2 as catalyst, form allylic amination products in excellent yields and selectivities when catalyzed by complex la generated in sim (Scheme 15). The scope of the reactions of aromatic amines is broad. Electron-rich and electron-neutral aromatic amines react with allylic carbonates to form allylic amines in high yields and excellent regio- and enantioselectivities as do hindered orlAo-substituted aromatic amines. Electron-poor aromatic amines require higher catalyst loadings, and the products from reactions of these substrates are formed with lower yields and selectivities. 

---