Steric effects allylic substitution

Examples of effects of reactant stmcture on the rate of nucleophilic substitution reactions have appeared in the preceding sections of this chapter. The general trends of reactivity of primaiy, secondary, and tertiaiy systems and the special reactivity of allylic and benzylic systems have been discussed in other contexts. This section will emphasize the role that steric effects can pl in nucleophilic substitution reactions. 

The reaction of aryldiazoacetates with cyclohexene is a good example of the influence of steric effects on the chemistry of the donor/acceptor-substituted rhodium carbenoids. The Rh2(reaction with cyclohexene resulted in the formation of a mixture of the cyclopropane and the G-H insertion products. The enantios-electivity of the C-H insertion was high but the diastereoselectivity was very low (Equation (31)). 0 In contrast, the introduction of a silyl group on the cyclohexene, as in 15, totally blocked the cyclopropanation, and, furthermore, added sufficient size differentiation between the two substituents at the methylene site to make the reaction to form 16 proceed with high diastereoselectivity (Equation (32)).90 The allylic C-H insertion is applicable to a wide array of cyclic and acyclic substrates, and even systems capable of achieving high levels of kinetic resolution are known.90... 

The acyclic version of Larock s heteroannulation was successfully applied to the synthesis of highly substituted pyridines [166]. The annulation of rert-butylimine 210 with phenyl propargyl alcohol produced pyridine 211 regioselectively in excellent yield. The regiochemistry obtained was governed by steric effects. Furthermore, the choice of imines was crucial to the success of the heteroannulations. terr-Butylimine was the substrate of choice, since all other imines including methyl, isopropyl, allyl and benzyl imines failed completely to produce the desired heterocyclic products. 

Similarly to the triphenylmethyl system, captodative-substituted 1,5-hexa-dienes, which can be cleaved thermally in solution into the corresponding substituted allyl radicals [15], dissociate more easily than dicaptor-substituted systems (Van Hoecke et al., 1986). Since ground-state and radical substituent effects cannot be separated cleanly, not only because of electronic but also because of steric effects, a conclusive answer cannot be provided. 

Finally, steric effects have an important influence on regioselectivity. This is very clearly demonstrated, for example, in the case of allyl carbanions substituted with silyl groups16. Therefore, despite wide investigation of this topic17, understanding of regiocontrol is still very poor, due to the complexity of the situation. 

Steric effects similar to those shown in equations (39) and (40) are found when the substitution pattern leads to tetrahydropyran systems through 6-endo cyclization. Cyclizations of systems with an allylic oxygen and a syn alkene substituent give products rationalized by cyclization through H-in-plane conformations as shown earlier in equations (31) and (32).105 128 Examples with allylic methyl substitution have been reported also.1040... 

Three research groups discovered almost at the same time that non-C2-symmetrical oxazolines of the type 32 can be even more effective ligands for asymmetric catalysis than type 4 ligands (Fig. 11). For the palladium-catalyzed allylic substitutions on 62, record selectivities could be reached using 32 (X = PPhj) [30]. It seems that not only steric but also electronic factors, which cause different donor/acceptor qualities at the coordination centers of the ligand, seem to play a role here [31]. The reaction products can subsequently be converted to interesting molecules, for example 63 (Nu = N-phthalyl) can be oxidized to the amino acid ester 64 [32]. 

Related chemistry of a cationic rf-a- yrm Mo(ll) complex is shown in Scheme 28. Hydride addition to the cationic reactant complex gives a neutral allyl-Mo that is oxidized by pyridinum dichromate (PDC) to a cation. Nucleophilic addition of water and oxidative decomplexation of the Mo fragment gives an enone. Substituted a-pyran hgands follow one of two paths depending on the electronic and steric effects of the substituent, as shown. 

Chirahty transmission can also be induced in thio-Claisen reactions by a chiral center adjacent to the allyl vinyl sulfide core. The group of Metz-ner examined the diastereoselectivity of the rearrangement of acyclic S-allyl ketene dithioacetals bearing a chiral center adjacent to carbon 6. hi these substrates, the sigmatropic shift proceeded smoothly and with modest syn anti diastereoselectivity [74]. In contrast, higher selectivities are foimd for thio-Claisen precursors bearing a chiral center adjacent to carbon 1 mainly due to steric effects and allylic strain [75]. In 1991, the group of Beslin examined the effect of a hydroxyl substituted chiral center attached to C-1 of Z and E S-allyl ketene dithioacetals [76,77] (Scheme 7). Under the reaction conditions, these... 

Pd-catalyzed allylic substitutions such as the Tsuji-Trost reaction have been investigated widely, essentially in their asymmetric version [44]. This represents a valuable tool in organic synthesis since the catalyst can accommodate various functionalities on the substrate and it is possible to tune the coordination sphere through the electronic and steric effects of the ligands. Those which contain a sulfur atom are based on an oxazoline backbone, and an ee as high as 96 % has been... 

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