Asymmetric reactions nucleophilic substitution, allylic derivatives

Although Helmchen et al. showed that asymmetric iridium-catalyzed allylic substitution could be achieved, the scope of the reactions catalyzed by iridium complexes of the PHOX ligands was limited. Thus, they evaluated reactions catalyzed by complexes generated from [lr(COD)Cl]2 and the dimethylamine-derived phosphoramidite monophos (Scheme 8) [45,51]. Although selectivity for the branched isomer from addition of malonate nucleophiles to allylic acetates was excellent, the highest enantiomeric excess obtained was 86%. This enantiomeric excess was obtained from a reaction of racemic branched allylic acetate. The enantiomeric excess was lower when linear allylic acetates were used. This system catalyzed addition of the hthium salts of A-benzyl sulfonamides to aUylic acetates, but the product of the reaction between this reagent and an alkyl-substituted linear aUylic acetate was formed with an enantiomeric excess of 13%. 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

The formation of chromane derivatives has also been realised in the palladium catalyzed intramolecular nucleophilic substitution of allyl carbonates (Tsuji-Trost reaction). In most cases the reaction is accompanied by the formation of a new centre of chirality. Using Trost s chiral ligand the ring closure was carried out in an enantioselective manner. The asymmetric allylation of the phenol derivative shown in 4.20. was achieved both in good yield and with excellent selectivity.23... 

The various possibilities for the preparation of chiral allylic amines or a aryl substituted amines are outlined in Figure 1.9. Although the addition reaction of a carbon nucleophile to an imine derived from an aryl substituted aldehyde is very efficient (B), the related addition to an a,p unsaturated imine (A) can sometimes proceed via a 1,4 addition pathway. Similarly, the asymmetric C=N reduction reaction (C and D) is sometimes hampered by the possibility of either obtaining conjugate reduction (in the case of C) or low enantioselectivities (in D when R = aryl). The addition of sp hybridized carbanions to imines (E) is a particularly effective... 

Asymmetric Allylation Reactions. Enantioselective allylic alkylation is used extensively in asymmetric synthesis with chiral nonracemic phosphines often serving as the source of enantio-discrimination. A monodentate phosphabicyclononane derivative in conjunction with Pd(dba)2 was found to be effective in promoting the asymmetric allylation of 2-substituted cyclopen-tenyl and cyclohexenyl carbonates with malonate and sulfonamide nucleophiles with ee s ranging from 50 to 95% (eq 16). ... 

KHMDS has been used to effect a-deprotonation of O-sUyl protected cyanohydrins derived from 2-/7-tolylsulfinyl henzalde-hyde followed by trapping of the C-nucleophile with diverse C-electrophiles, providing a powerful alternative approach to cyanohydrins of ketones. The remote 1,4-asymmetric induction was equally effective for either epimer (diastereomer) of the 0-TIPS protected cyanohydrin, and an equimolar mixture of the two epimers was employed. Both KHMDS and LHMDS bases provided the substituted cyanohydrins from reactions with highly reactive electrophiles (ClCOOMe and ClCOMe) in excellent yields and diastereoselectivities (dr > 98 2) (eq 65). The deprotonation induced by KHMDS led to more reactive nucleophiles, shortening the reaction times. Notably, in alkylations of Eschen-moser s salt, and benzyl and allyl bromides, the application of LHMDS instead of KHMDS improved the diastereoselectivity. The stereoselectivity of the alkylations mediated by KHMDS could be increased by the inclusion of the 18-crown-6 ether... 

Catalytic reactions of allylic electrophiles with carbon or heteroatom nucleophiles to form the products of formal S 2 or S 2 substitutions (Equation 20.1) are called "catalytic allylic substitution reactions." Tliese reactions have become classic processes catalyzed by transition metal complexes and are often conducted in an asymmetric fashion. The aUylic electrophile is typically an allylic chloride, acetate, carbonate, or other t)q e of ester derived from an allylic alcohol. The nucleophile is most commonly a so-called soft nucleophile, such as the anion of a p-dicarbonyl compound, or it is a heteroatom nucleophile, such as an amine or the anion of an imide. The reactions with carbon nucleophiles are often called allylic alkylations. 

The Pd-catalyzed reactions of allylic electrophiles with metal nucleophiles can produce the corresponding allylmetal derivatives (Sect. V.233), which can, in turn, serve as allylic nucleophiles. This protocol provides a means of utilizing allylpalladium and related derivatives as nucleophiles rather than electrophiles (Sect. V.23.4). Many of the substitution reactions mentioned above can be asymmetric. Because of their special significance in organic synthesis, Pd-catalyzed asymmetric allylation and related reactions are discussed in Sect. V.2.4. 

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