Substitution reactions allylic substrates

Hie use of tlie cliiral catalyst 19b for asymmetric allylic substitution of allylic substrates bas been studied in some deta d fSdieme 8.18) and, under ji-selective reaction conditions, asymmetric induction was indeed obtained [28, 34]. 

The stereochemistry of the direct substitution reaction has been the subject of some debate. Most recently, it has been reported that reactions of alkylheterocuprates proceed with high syn selectivity, while inversion of allenyl configuration, or anti selectivity, is observ in reactions of phenylcopper reagents. The degree of selectivity is variable and may be a reflection of product isomerization under the reaction conditions. Predominant anti stereoselectivity (anti syn ratios range from 91 9 to >99 1) is observed also in Sn2 reactions of allenyl halides (see Scheme 3), a finding that is consistent with the known preference for anti substitution of allylic substrates (see Section I.5.2.4.5). This method for al-kyne preparation has found application in the leukotriene area, and also for the synthesis of alkoxy al-kynes. ... 

A similar triarylphosphane was introduced by Leitner for the performance of transition metal catalyzed reactions in supercritical CO2 [24]. Recently, this phosphane was used for palladium catalyzed substitutions of allylic substrates in perfluorinated solvents under fluorous biphase conditions [25], Therefore, the reaction of cinnamyl methylcarbonate (36) with several nucleophiles (Nu-... 

Palladium-catalyzed nucleophilic substitution of allylic substrates (Tsuji-Trost coupling) is a most important methodology in organic synthesis and therefore it is no wonder that such reactions have been developed also in aqueous systems. Carbo- and heteronucleophiles have been found to react with allylic acetates or carbonates in aqueous acetonitrile or DMSO, in water or in biphasic mixtures of the latter with butyronitrile or benzonitrile, affording the products of substitution in excellent yields (Scheme 6.19) [7-11,14,45,46], Generally, K2C03 or amines are used as additives, however in some cases the hindered strong base diazabicycloundecene (DBU) proved superior to other bases. 

The palladium-mediated substitution of allylic substrates proceeds in two independent steps. For stabilized carbanions both oxidative addition and the nucleophilic displacement occur with inversion of configuration. Thus, overall retention results, in contrast to the corresponding reactions of nonstabilized carbanions as nucleophiles (see Section D.l. 5.6.3.). The steric course of the reaction is proved by the absence of racemization in Lhe conversion of chiral substrates into chiral alkylated products. Furthermore, chiral n-allylpalladium complexes formed with inversion from stoichiometric reactions of palladium(O) with allyl substrates have been isolated. Coupling of these stereodefined complexes with soft carbanions yields the chiral alkylated products, again with inversion of configuration. 

An example that appears to be electronically controlled involves the allylic substitution reactions of substrate 112 and related structures (Scheme 20). The para-substituents exert a strong electronic influence but are expected to be similar on steric grounds. The nucleophiles attack selectively away from the electron-deficient nitro group. 

Chlorobutyl rubber is prepared by chlorination of butyl rubber (chlorine content is about 1 wt%). This is a substitution reaction produced at the allylic position, so little carbon-carbon double unsaturation is lost. Therefore, chlorobutyl rubber has enhanced reactivity of the carbon-carbon double bonds and supplies additional reactive sites for cross-linking. Furthermore, enhanced adhesion is obtained to polar substrates and it can be blended with other, more unsaturated elastomers. 

Hie use of chiral catalysts as an approach to enantiomer icaliy enriched products by means of coppet-mediated substitution reactions is covered in this chapter. Reactions in which a chiral auxiliary resides in the leaving group of the substrate w ill also he dealt with, since these reactions provide direct and efBcient routes to single enantiomers of the desired products. Most studies so far have been concerned with allylic substrates, with a new chiral center being produced in the course of a selec-... 

Depending on the substrate and the other reaction parameters, very higli re-gioselectivilies towards either a or y suhstilution can he obtained. In cetLain cases, the regioselectivity can easily he switclied between the two modes by changing the reaction conditions [11]. Compared to, for example, palladiumiO)-catalyzed allylic substitution reactions, the possibility of switching between S j2 and S j2 selectivity... 

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. 

Denniatk and co-wotkets teporied tlie brst example in 1990 [16], using substrates 1, s7ntliesized Grom adiital allylic alcohols and tead dy ava dable optically active amine auxdiaries. Substrates 1 were tlien employed in coppet-niediaied allylic substitution reactions, as shown in Sdienie 8.4. 

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. 

Scheme 1.47 Arenethiolatocopper(I)-catalysed substitution reactions of RMgX with allylic substrates.

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... 

More recently, Backvall et al. have reported the use of arenethiolatocopper(I) as a catalyst for the analogous substitution reaction of Grignard reagents with allylic substrates. In this case, the crosscoupling reaction could occur in an a(SN2) or y(Sn2 ) manner, depending on the reaction conditions. In all cases, the y-product was isolated as the sole product with moderate to quantitative... 

As shown in Scheme 2.20, selective lithiation of substrate 2-87 by treatment with LDA in THF at -78 °C triggers an intramolecular Michael/intermolecular aldol addition process with benzaldehyde to give a mixture of diastereomers 2-90 and 2-91. 2-91 was afterwards transformed into 2-92, which is used as a chiral ligand for Pd-catalyzed asymmetric allylic substitution reactions [29]. 

---