Allylic selectivity rules

More than a decade of experience on Sharpless asymmetric epoxidation has confirmed that the method allows a great structural diversity in allylic alcohols and no exceptions to the face-selectivity rules shown in Fig. 10.1 have been reported to date. The scheme can be used with absolute confidence to predict and assign absolute configurations to the epoxides obtained from prochiral allylic alcohols. However, when allylic alcohols have chiral substituents at C(l), C(2) and/or C(3), the assignment of stereochemistry to the newly introduced epoxide group must be done with considerably more care. 

Kinetic resolution of chiral aUylic alcohols.7 Partial (at least 60% conversion) asymmetric epoxidation can be used for kinetic resolution of chiral allylic alcohols, particularly of secondary allylic alcohols in which chirality resides at the carbinol carbon such as 1, drawn in accordance with the usual enantioface selection rule (Scheme I). (S)-l undergoes asymmetric epoxidation with L-diisopropyl tartrate (DIPT) 104 times faster than (R)-l. The optical purity of the recovered allylic alcohol after kinetic resolution carried to 60% conversion is often > 90%. In theory, any degree of enantiomeric purity is attainable by use of higher conversions. Secondary allylic alcohols generally conform to the reactivity pattern of 1 the (Z)-allylic alcohols are less satisfactory substrates, particularly those substituted at the /1-vinyl position by a bulky substituent. 

The selection rules can be applied to charged species as well as to neutral molecules. The only requirement is that the reaction be a concerted process involving electrons in overlapping p orbitals. For example, the conversion of a cyclopropyl cation to the allyl cation can be considered as a tt -electrocyclic process. For this process, the selection rules predict a disrotatory process. 

These predictions involve some assumptions and approximations when applied in a generalised form. Thus symmetry is lacking in most reactants in cycloadditions, either because of different substitution at identical atoms (for instance vinyl derivatives instead of ethylene) or because different atoms are present as reactions centers (as in most 1.3-dipoles). In the former case the substance of the previous considerations should be unaltered , but in the latter case the selection rules (e.g. derived for the allyl anion taken as model of 1,3-dipole) may be less stringent when applied only on the basis of analogy. 

As is the case for other pericyclic reactions, the selection rules for a thermal [i, ] sigmatropic reaction are reversed for the photochemical reaction. If irradiation of a 1,5-hexadiene produces the electronically excited state of one and only one of the two allyl components, then the HOMO of one component is (/f3, and the HOMO of ihe other component is suprafacial-suprafacial reaction (Figure 11.46) is forbidden (as is the antarafacial-antar-afacial pathway), but the antarafacial-suprafacial and suprafacial-antarafacial pathways are allowed (Figure 11.47). Analysis of higher sigmatropic reactions shows that the selection rules also reverse with the addition of a carbon-carbon double bond to either of the n systems. Thus, the [3,5] sigmatropic reaction is thermally allowed to be suprafacial-antarafacial or antarafacial-suprafacial and photochemically allowed to be suprafacial- suprafacial or antarafacial-antarafacial. Two of these reaction modes are illustrated in Figure 11.48. 

It is important to note that the selection rule in Table 11.1 refers to the number of electrons in the systems undergoing pericyclic change, not for the number of orbitals. Thus, the addition of an allyl anion to an alkene, the addition of an allyl anion to an allyl cation, and the addition of a pentadienyl cation to an alkene are all [4 -I- 2] cycloadditions (Figure 11.71). ... 

Normally, the addition of C-nucleophiles to chiral a-alkoxyaldehydes in organic solvents is opposite to Cram s rule (Scheme 8.15). The anti-Cram selectivity has been rationalized on the basis of chelation control.142 The same anti preference was observed in the reactions of a-alkoxyaldehydes with allyl bromide/indium in water.143 However, for the allylation of a-hydroxyaldehydes with allyl bromide/indium, the syn isomer is the major product. The syn selectivity can be as high as 10 1 syn anti) in the reaction of arabinose. It is argued that in this case, the allylindium intermediate coordinates with both the hydroxy and the carbonyl function leading to the syn adduct. 

This disadvantage can be ruled out by spacers between the allylic and the acrylic group [15], but the selectivity in favor of the allylic group is not improved. An acetylenic triple bond instead helps to clarify the situation. 2-Propynoxyethyl acrylate, available in 90 % yield from ethoxylated propargylic alcohol by esterification, is hydrosilylated very smoothly only at the triple bond, leaving the acrylic side virtually untouched (Eq. 5). 

BM Trost. New rules of selectivity allyl alkylations catalyzed by palladium. Acc Chem Res 13, 385, 1980. 

The presence of a stereogenic center at Cj of an allylic alcohol introduces an additional factor into the asymmetric epoxidation process in that now both enantiofacial selectivity and dias-tereoselectivity must be considered. It is helpful in these cases to examine epoxidation of each enantiomer of the allylic alcohol separately. Epoxidation of one enantiomer proceeds normally and produces an erythro epoxy alcohol in accord with the rules shown in Figure 6A.1. 

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