Primary stereoelectronic effect

Intermediate 69 can either yield aZ (hydroxy-ester) or an E (lactone) ester. Intermediate 70 can only yield an E ester (lactone) whereas intermediate 7 can produce two esters, the hydroxy-ester having an E conformation and the lactone. Thus, primary stereoelectronic effects allow the cleavage of intermediates 69-71 to produce either the hydroxy-ester or the lactone prod-... 

Goodman, R. M., Kishi, Y. Experimental Support for the Primary Stereoelectronic Effect Governing Baeyer-Villiger Oxidation and Criegee Rearrangement. J. Am. Chem. Soc. 1998, 120, 9392-9393. 

Reiser, O. A demonstration of the primary stereoelectronic effect in the Baeyer-Villiger oxidation of -fluorocyclohexanones. Chemtracts 2001, 14, 94-99. 

Examples of the primary stereoelectronic effect have been demonstrated in the literature. Chandrasekhar and Roy showed that rearrangement of 2-oxo-cyclohexyl-peroxyacetic acid 35, derived from acid 34, proceeded via intermediates 36 and 37 to 38 in 62% overall yield.17 Migration of bond a was the only bond which migrated being antiperiplanar to the peroxide no product of migration of bond b was observed. 

The trans bicyclic orthoester must exist in the conformation 95 and the primary stereoelectronic effects permit the ejection of the methoxy group Ohly, yielding the bicyclic lactonium ion which after hydration (-97) and cleavage will give the hydroxy-lactone % only. The process 97 - 90 cannot occur with stereoelectronic control its energy barrier must therefore be higher than in other cases. Kaloustian and Khouri (61) have shown that the reaction of sodium methoxide with the bicyclic salt % gave the trans orthoester specifically. 

The stereoelectronic components of the reaction have already been discussed above. For a long time it was assumed that the migrating group occupied an anti-periplanar position with respect to the dissociating oxygen-oxygen bond of the peroxide (see representation B in Scheme 9.3). Recent experimental studies confirmed this primary stereoelectronic effect (B ) and revealed that it is indeed, at least in part, responsible for the selectivity of the migration step [295]. 

The stereoelectronically controlled reaction of hydroxide ion with an 0-labeled tertiary amide(J8 ) (Fig. 3) should give the intermediate 19 which can fragment in only two ways, yielding the starting labeled amide J8 or the hydrolysis products direct cleavage of W to give unlabeled amide 18 cannot take place with the help of the primary electronic effect. In order to form the unlabeled amide J8 with stereoelectronic control, intermediate Jj) must first be converted into another conformer such as 20. Oxygen... 

The principle of microscopic reversibility predicts that the reverse process must follow the same path which is indeed stereoelectronically allowed the oxygen atom in T has two secondary electronic effects (n-o ) (one electron pair of the oxygen atom is anti peri planar to the C-N bond while the other is antiperiplanar to C —Y bond) and the nitrogen has one (the nitrogen electron pair is antiperiplanar to the C —Y bond). Thus, there are three secondary electronic effects (n-o ) in ] and by the ejection of Y to form 4, two of these (due to the two electron pairs antiperiplanar to the C—Y bond) have been transformed into primary electronic effects (n- ) in the product 4. The third secondary electronic effect remains a n-o interaction in the product. The ejection of Y can therefore take place with the help of the primary and one secondary electronic effects. 

A detailed examination of the cleavage in conformers A, B, and C follows. Interestingly these three are the only conformers generated directly from reaction of alkoxide ion on a tertiary amide, with stereoelectronic control. Cleavage of conformer A can only lead to the tertiary amide, as the ejection of the amino group cannot occur with the help of the primary electronic effect (the 0 —R bond is antiperiplanar to the C-N bond). Conformer J3... 

In this publication the author describes the phenomenon that most times the thermodynamically less stable product (see 29) of the two possible rings (e.g. 5-exo and 6-endo) is formed. Today looking at the 5-exo cyclization it is known that, although the generated primary radical is less stable than a secondary one, stereoelectronic effects favor reaction to the kinetically controlled product. According to MO-calculations, for a successful cyclization, an angle of 70° of the incoming radical to the plane of the alkene-/alkyne-bond is necessary.11... 

In another study, tertiary secondary primary relative reactivity data (TSP selectivity) for the deprotonation reactions of alkylbenzene radical cations [ 153] showed that with both intra- and intermolecular TSP selectivity the order S > T > P is usually observed, suggesting that the combination of steric and stereoelectronic effects makes an /Pr group less reactive than Et, but still more reactive than Me. 

Lactone is reacted with trimethyloxonium tetrafluoroborate (Me30+BF4 ). The produce is next refluxed with sodium iodide in acetone until complete disappearance of the 5-lactone. By taking entropy effects, stereoelectronic effects and the relative ease of SN2 reaction on primary versus secondary v.v tertiary carbons into consideration, comment on the possible product(s) profile. 

While the primary and secondary stereoelectronic effects have been invoked to rationalize products,21 there have been reports in series of polycyclic ketones in which regiochemistry of migration was not explained by these effects.22... 

The cyclization of the 5-hexenyl radical to cyclopentylmethyl (Entry 33) is a commonly observed reaction. The is 6 kcal/mol. The cyclization shows a preference for exo cyclization to a five-membered ring over endo cyclization to a six-membered ring/ even though it results in formation of a less stable primary radical. The cause for this preference has been traced to stereoelectronic effects. In order for a bonding interaction to occur, the radical center must interact with the it orbital of the alkene. According to MO calculations, the preferred direction of attack is from an angle of about 70° with respect to the plane of the double bond. ° ... 

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