Displacement reactions involving participation

Goodman has reviewed neighboring-group participation in Volume 22 of this Series,366 and this subject will therefore not be discussed comprehensively in the present article. However, Goodman specifically excluded from his review the formation of anhydro sugars by oxide ion displacements, and also the formation of anhydronucleosides ( cyclonucleosides ). These topics will therefore be discussed, together with ring contractions and alkoxyl participations, because most of the literature on these subjects has not been reviewed previously. 

Hartman and Barker have examined intramolecular displacements of p-tolylsulfonyloxy groups by oxide ions, and have concluded that 

A secondary p-tolylsulfonyloxy group is displaced most readily by an alkoxide ion derived from a primary a-OH. 

The determination of optimal reaction-conditions (greatly facilitated by the use of thin-layer chromatography) is often critical, as initial products may undergo further reactions this was demonstrated in syntheses of 2,3 4,5-dianhydro-D-iditol from 3,4-di-O-sulfonyl-D-mannitol derivatives.368 389 

Although most of the following subsections on oxide-ring formation deal with bi- and tri-cyclic systems which impose additional, and often overriding, steric constraints, cognizance should be taken of these fundamental considerations. 

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Kinetic isotope effect for lysozyme. A secondary kinetic isotope effect is expected because a molecule with H in the number 1 position can be converted to the corresponding oxocarbenium ion somewhat more easily than the molecule with 2H in the same position (Eq. 12-13). For example, in the nonenzymatic acid-catalyzed hydrolysis of a methyl- glucoside, a reaction also believed to proceed through a carbocation intermediate,41 75 the ratio h / h, is 1.14 for the a anorner and 1.09 for the (3 anorner.53 In the base-catalyzed hydrolysis of the same compound, which is believed to occur by a double-displacement reaction involving participation of the neighboring OH group on C-2, the ratio /c1h / /c2h is 1.03. The corresponding ratio measured... 

The initial suggestion that a remote double bond could be involved in a displacement reaction was made by Shoppee in 1946 in order to account for the stereochemical results of the transformations of 3-cholesteryl derivatives Building on the considerable work then underway on neighbouring group participation in ionization reactions Shoppee suggested that the double bond in the cholesteryl system, 1, could function in a similar manner to Lewis base containing groups such as acetate or alkoxy, etc. 

The first example of methoxyl participation reported in carbohydrate chemistry was the migration454 of a methoxyl group from C-l to C-4 during an attempted benzoate displacement reaction with 2,3,5-tri-O-benzyl-4-O-p-tolylsulfonyl-D-ribose dimethyl acetal (185). Instead of the 4-O-benzoyl-L-lyxose derivative expected, the isomeric l-0-benzoyl-2,3,5-tri-0-benzyl-4-0-methyl-L-lyxose methyl hemi-acetal (187) was obtained, presumably by way of the cyclic, oxonium ion 186. Solvolysis of the related aldehydo sugar, namely, 2,3,5-tri-O-benzyl-4-O-p-tolylsulfonyl-D-ribose, readily gives 2,3,5-tri-O-benzyl-L-lyxofuranose, and the reaction probably involves participation by the free aldehyde group.455... 

A number of ring transformations and reactions involving the displacement of substituents such as SMe-group in trifluoromelhyl containing 1,2,4-triazines have been described. A-substituted cyanamides participate in cycloaddition exclusively across C-5/N-2 of the 1,2,4-triazine nucleus 103 yielding the bicycle 104 as nonisol-able intermediate. Elintination of trifluoroacetonitrile leads to the 1,3,5-triazines 105 as the main reaction products. Besides, the 1,2,4-triazines 106 are formed by loss of methyl thiocyanate (Scheme 44) [28]. 

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