Nitrile effect

The stereodirecting nitrile effect [131,327-330] is also applicable to sulfoxide glycosylations with activation by triflic anhydride (Scheme 4.41) [279], even if selectivities remain modest for the formation of the 1,2-ds-equatorial class of glyco-sidic bond [329,331]. 

Furthermore, treatment of 438 with a series of nitriles effects cyclization to a variety of 2-substituted compounds 441 in low to modest yields (Equation 165) <1994IJB436>. 

Utilizing MeCN there is the possibility of a special solvent effect, directing to this converse selectivity, named nitrile effect.28,29 30... 

Starting with phosphite 59 stannous triflate catalyzes the formation of an oxenium ion 60, which is stabilized by the solvent (61). The complex 61 is more favored than 63, justified by the reverse anomeric effect until now. But as it is shown there is no possibility for 61 to react in an SN2 reaction to 62. The intermediate 63 can be attacked by the alcohol functionality of the glycosyl acceptor, and with MeCN as leaving group you get 64. Ultimately the equilibrium between 61 and 63 shifts completely to 63. This kind of stereocontrol during a glycosylation is known as the nitrile effect.28... 

Because of the absence of a participating group at C-2 of donor 57, and in order to obtain the f>-( 6) linkage, glycosylation was performed in a participating solvent such as acetonitrile (nitrile effect).116 The condensation of benzyl (2,3,5,6-... 

In addition, this reaction is an auto-catalyzed reaction, as demonstrated by the reaction between / -bromotoluene and CuCN, which at 250°C completes only 15% within the first 60 min, while 60% more product is formed in the subsequent 30 min of reaction. Moreover, the presence of a small amount of nitrile effectively reduces the induction period. Some nitrogenous bases such as tertiary amine and pyridine also promote this reaction. It has been found that CUSO4 has a catalytic effect for this reaction, whereas hydroquinone retards the formation of aromatic nitrile, indicating that this reaction involves the divalent copper ion. However, this reaction also has a few associated problems the requirement for extreme reaction conditions (150-280°C) a harsh work-up process by heating with HCl and FeCb a stoichiometric amount of cuprous cyanide which leads to the formation of equivalent amount of copper halide which may complicate the product separation and cause the problem of waste disposal as well. ... 

Hence, it was decided to increase the reactivity of the first sugar residue by replacing the phthalimido group by the azido group which showed the desired effect (49). However, introduction of glucosamine residues at the nonreducing end would be hampered because the stereocontrol with the help of the nitrile effect (50) was less pronounced on solid support than in solution (48). 

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