Acetate, neighbouring group participation

You ve already met the most important ones—sulfides, esters, carboxylates. Ethers and amines (you will see some of these shortly) can also assist substitution reactions through neighbouring group participation. The important thing that they have in common is an electron-rich heteroatom with a lone pair that can be used to form the cyclic intermediate. Sulfides are rather better than ethers—this sulfide reacts with water much faster than rc-PrCl but the ether reacts with acetic acid four times more slowly than rc-PrOSC Ar. 

Another of the four examples we started with shows that even the n electrons of a C C double bond can participate. Retention of stereochemistry in the product (the starting tosylate and product acetate are both anti to the double bond) and the extremely fast reaction (1011 times that of the saturated analogue) are tell-tale signs of neighbouring group participation. 

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. 

Neighbouring-group participation by a 5a-acetoxy-group in the substitution of a 3fi-OR group is paralleled by Sa-acetylthio-groups. The crystalline 3a,5a-cyclic onium perchlorate (31) was generated by reaction of the 3j9-hydroxy-compound (29) with acetic anhydride-sulphuric acid [via the 3/1-acetyl sulphate (30)], followed by the addition of perchloric acid. Hydrolysis of the onium salt gave the 3a-acetoxy-5a-thiol (32). 

An unusual substitution with neighbouring-group participation occurred when the 3o -chloro-2)S,19-oxido compound (51) was treated with either zinc metal or sodium acetate in acetic acid. ° j8-Face participation by the ether oxygen (52) led to nucleophilic attack at the 2a- and 3a-positions, forming both the 3a-acetoxy-2j8,19-oxido- (53) and the 2a-acetoxy-3) ,19-oxido-compounds (54). 

A number of non-stereospecific acetate and xanthate pyrolyses have been observed " . /4 t/-elimination is rationalised by invoking neighbouring-group participation by an appropriately situated methyl ester group in one case . The array of products arising from one of the xanthate pyrolyses can be accounted for in terms of competing heterolytic and homolytic eliminations . The pyrolyses of isothiocyanates and thiocyanates bear a close resemblance to the ester eliminations " . 

A novel variation on the Hanesslan-type reaction of certain benzylldene acetals with N -bromosuccinimide involves neighbouring-group participation by a trichloroacetlmidoyl group in the opening of an intermediate dloxolanylium ion. The reaction has been applied to the synthesis of the 3-amino-l,6-anhydro-3-deoxy-6-D-... 

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