Stereochemistry with cyclic transition structures

The observed activation of allyltrihalosilanes with fluoride ion and DMF and the proposition that these agents are bound to the silicon in the stereochemistry-determining transition structures clearly suggested the use of chiral Lewis bases for asymmetric catalysis. The use of chiral Lewis bases as promoters for the asymmetric allylation and 2-butenylation of aldehydes was first demonstrated by Denmark in 1994 (Scheme 10-31) [55]. In these reactions, the use of a chiral phos-phoramide promoter 74 provides the homoallylic alcohols in high yield, albeit modest enantioselectivity. For example, the ( )-71 and benzaldehyde affords the anti homoallylic alcohol 75 (98/2 antUsyn) in 66% ee. The sense of relative stereoinduction clearly supports the intermediacy of a hexacoordinate silicon species. The stereochemical outcome at the hydroxy center is also consistent with a cyclic transition structure. 

The methyl ester was crystallized and its absolute stereochemistry was determined by x-ray diffraction to be as in equation 8.37. This product corresponds to an in-line attack. When incubated with ribonuclease in aqueous solution, the methyl ester re-forms the original cyclic phosphorothioate (structure 8.36). This result is expected from the principle of microscopic reversibility, since the forward and reverse reactions must go through the same transition state. But it does show directly that the cyclization step involves an in-line attack an adjacent attack of the ribose hydroxyl in the cyclization of the methyl ester as in the right-hand structure 8.38 would give the enantiomer of structure 8.36. 

The reaction of racemic 147 with (R)-carvone, initially at -78 °C followed by warming to room temperature for 1 h, gave the vinylcyclopropane 151 in 72% yield and moderate diastereoselectivity (d.r. = 75 25). The stereochemistry of the major diastereoisomer shown in structure 151 from H NMR studies was that expected based on the stereochemical outcome of the reaction of racemic 147 with the achiral cyclic enones 146 and is consistent with our previously proposed chelated transition state90 for cyclic enones (compare with the transition state B). 

Three levels of explanation have been advanced to account for the patterns of reactivity encompassed by the Woodward-Hoffmann rules. The first draws attention to the frequency with which pericyclic reactions have a transition structure with (An + 2) electrons in a cyclic conjugated system, which can be seen as being aromatic. The second makes the point that the interaction of the appropriate frontier orbitals matches the observed stereochemistry. The third is to use orbital and state correlation diagrams in a compellingly satisfying treatment for those cases with identifiable elements of symmetry. Molecular orbital theory is the basis for all these related explanations. 

Kinetic studies of the Midland reduction confirmed that the reduction of aldehydes is a bimolecular process and the changes in ketone structure have a marked influence on the rate of the reaction (e.g., the presence of an EWG in the para position of aryl ketones increases the rate compared to an EDG in the same position). However, when the carbonyl compound is sterically hindered, the rate becomes independent of the ketone concentration and the structure of the substrate. The mechanism with sterically unhindered substrates involves a cyclic boatlike transition structure (similar to what occurs in the Meerwein-Ponndorf-Verley reduction). The favored transition structure has the larger substituent (Rl) in the equatorial position, and this model correctly predicts the absolute stereochemistry of the product. 

The ring closure of cyclic 2-but-3-enylcycloalkyl radicals (Fig. 7.3) is similar to that of the open-chain system, except that the constraints of the ring impose an almost exclusive 1,2-cis stereochemistry [3, 4]. The critical 1,5-selectivity is still largely cis, and it is this selectivity that has found the most use in the synthesis of polycyclic natural products [5, 6]. In the context of the 2-but-3-enylcyclopentyl radical cyclization, it was argued [7] that the l,5-c stereochemistry is favored because the chair-like transition structure 8a (Fig. 7.4) can achieve effective overlap between the SOMO and the radical center and the olefin n orbitals, with less strain than the other possible chair Sb. 

Another use of stereochemistry is a technique known as the endocyclic restriction test. In this procedure a cychc molecule is constructed so that two substituents might react with each other in a mechanism analogous to a bimolecular reaction. However, because the transition structure for the reaction must be cyclic, only one of two possible mechanisms is sterically feasible. Determining whether the intramolecular reaction can occur for transition structures with various ring sizes provides some insight into the probable geometry of the reactants in the bimolecular reaction. For an example, see Li, J. Beak, P. /. Am. Chem. Soc. 1992,114,9206. See also Beak, P. Acc. Chem. Res. 1992, 25, 215 Pure Appl. Chem. 1993, 65, 611. 

If an alkene has a hydroxyl (or other functional group capable of donating a proton in a hydrogen bonding interaction) in the allylic position, that group can affect the stereochemistry of the epoxide product. For example, reaction of cyclic allylic alcohols produces a 10 1 ratio of product with the epoxide cis to the alcohol fimction (equation 9.55) relative to the trans product. This diastereoselectivity has been attributed to hydrc en bonding in the transition structure for the epoxidation (Figure... 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

The transition-state structure must be the distorted chair-like species which most likely generated the cyclic diene from cw-l,2-divinylcyclobutane. This would, therefore, preserve the stereochemistry of groups attached to the terminal vinyl groups. Thus, this reaction could not be responsible for Berson s observation with CCC (see part 1 of this section). 

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