Transition states allylic halide reactions

The high reactivity of allylic halides in SN2 reactions indicates some special stabilization of the transition state ascribable to resonance involving the adjacent tt bond. We can express this in terms of the valence-bond structures, 2a-2c, for the transition state of the reaction of iodide ion with 3-chloropropene (Section 8-7A). The extra stabilization over the corresponding transition state for the reaction of iodide with a saturated chloride (e.g., CH3CH2CH2C1 + 1 ... 

When we are considering a question involthng reaction rates, the answer can always be found through an analysis of the transition states. The rate is dependent on the activation energy for the reaction, which is the height of the transition state relative to the starting halide. Let s compare the transition state for the reaction of a 1-propyl halide with that for the reaction of an allyl halide (Fig. 12.49). 

Benzyl halides are also especially reactive in the Sn2 reaction. The reason is the same as that for the enhanced reactivity of allyl chloride (p. 543).The transition state for Sn2 displacement is delocalized, and therefore especially stable. If the transition state for a reaction is at relatively low energy, the activation energy for the reaction will also be relatively low and the reaction will be fast (Fig. 13.73). 

When Lewis acids such as SnCU and TiCU are used to promote additions of allylic trialkyltin reagents to aldehydes several reaction outcomes are possible, depending on stoichiometry and the mode of addition. If the Lewis acid is added to the aldehyde followed by the allylic stannane, the typical product (syn for crotylstannanes) derived from an acyclic transition state is formed. If, however, the stannane and Lewis acid are premixed and left to equilibrate, metathesis can occur forming the allylic halome-tal compound which reacts with the subsequently added aldehyde to give products (anti for crotyl) consistent with a cyclic transition state (Eq. 22). The initially formed allylic halostannane gives rise to the linear adduct, but if aldehyde addition is delayed, this initial secondary allylic metal halide can equilibrate to the primary isomer which then reacts with the aldehyde to afford the branched product. 

Butyltin halides have also been used to mediate this process. One of the first examples involved addition of a 3 1 mixture of tram- and ds-crotyl tributyltin and a variety of conjugated aldehydes to Bu2SnCl2 without solvent to form (Z) homoallylic linear adducts (Table 22) [39], In this reaction, addition of the initially formed secondary allylic dibutylchlorostannane to the aldehydes must be faster than that of the tributyl crotylstannanes, and faster than 1,3-isomerization of the chlorostannane. Formation of the (Z) isomer is consistent with a chair transition state in which the allylic methyl group of the stannane adopts an axial orientation to avoid steric interactions with the adjacent stannane substituents (Eq. 23). 

The accidental observation in 1957 that allyl halides reacted with tin hydrides not by addition across the double bond, but by replacement of the halogen by hydrogen, provided the basis for the extensive use which the tin hydrides (Section 15.3.5), distannanes (Section 18.2.3), allylstannanes (Section 9.1.3.3), and related compounds now find in organic synthesis. The reaction involves bimolecular homolytic substitution (Sh2) at the halogen centre, and ab initio calculations indicate that, when R = H, R = Me, and X = Cl, Br, or I, the transition state is colinear, as illustrated in equation 20-18.58... 

As mentioned in the discussion of the pathways to indoles (Scheme 27), a detailed indole synthesis with two points of diversity based on the Heck reaction has been reported [164]. The indole core structure was synthesized via a 5-exo-tng transition state, which provided the exocyclic double bond that subsequently underwent exo to endo double-bond migration. The anthranilate building block was prepared in solution and immobilized by a method previously described for the loading of 2-aminobenzophenones [Ij. After Fmoc cleavage, the resulting 4-bromo-3-amino-phenyl ether was treated with acid chlorides and pyridine in CH2CI2. As outlined in Scheme 29, alkylation of the anilide with substituted allyl bromides was achieved in the presence of lithium benzyloxazoHdinone in THF. The reaction mixture was treated with base for 1 h and then an aUylic halide was added and the mixture was vortexed for 6 h at room temperature. The alkylation reactions were... 

In other words, neopentyl bromide reacts even more slowly than the tertiary bromide because the transition state is more sterically crowded and higher in energy. The result with neopentyl bromide stands in sharp contrast to both allyl bromide (3-bromo-l-propene, CH2=CHCH2Br) and benzyl bromide (PhCH2Br note the use of Ph to abbreviate the benzene ring), which show increased rates of the reaction. If it is assumed that the activation energy is lower for these reactions, why is it lower The 7r-bond in both of these molecules helps to expel the bromide, as illustrated by 15. In other words, the 7i-bond participates in the reaction, in the transition state. This 7t-bond-assisted increase in the rate of the reaction makes the Sn2 reaction for both the allylic halide and the benzyl halide faster than a simple primary alkyl halide. 

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