Activations orthoesters

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

When neighboring-group participation is a feature of the glycosylation reaction, the use of a base in this manner frequently results in the isolation of orthoesters rather than the desired glycosides. In the case of activation by triflic anhydride, it is possible to avoid this problem by simply omitting the base. Alternatively, with more sensitive substrates, the hindered base may be retained and boron trifluoride ethe-rate be added to promote the rearrangement of the orthoester to the glycoside, as in... 

This class of donor is activated by soft Lewis acids, such as copper triflate at room temperature, and despite their hydrolytic instability, they appear inert to conditions of sulfoxide activation, TMSOTf or Tf20 (Scheme 4.53). Activation is achieved with stoichiometric promoter in the presence of the acceptor alcohol, and although the mechanism has not been investigated, presumably it proceeds via coordination followed by collapse to a stabilized oxacarbenium ion. The method is compatible with standard glycosidation solvents such as dichloromethane, acetonitrile and diethyl ether, and ester-directed couplings do not lead to orthoesters, perhaps as a result of the presence of the Lewis acid promoter [303,304]. 

The peptidyltransferase reaction. It has been difficult to establish whether the 2 or the 3 of the terminal adenosine of tRNA carries the activated aminoacyl or peptidyl group. Rapid equilibration between the two via an orthoester may occur (Eq. 29-10), and EF-Tu of E. coli binds to either the 2 or 3 isomer.386 3863 However, reaction of the 3 -aminoacyl-tRNA at the peptidyltransferase site is probable.387 3873 4 ... 

The cyclization of a-hydrazono oximes (635) with orthocarboxylates is an excellent way of preparing 1,2,4-triazine 4-oxides (636) (73TL1429,7lLA(750)12,77LA1713). Using aldehydes or ketones instead of orthoesters provides 2,3-dihydro derivatives (637 Scheme 22) (75S794). Cyclization of a-hydrazonocarboxamides (638) with carbonic acid derivatives such as ethyl chloroformate affords l,2,4-triazine-3,5-diones (639) (68M1808). The a-hydrazonocarboxamides (638) can be prepared by the reaction of diazonium salts with a-activated acetamides such as cyanoacetamide as shown. 

Mannosides of phosphatidylinositol are important serologically active components of Mycobacterium tuberculosis. For the synthesis of the 2-O-mannosyl derivative (421), Stepanov et al. [291] treated the chiral prop-l-enyl ether (414) [and the corresponding racemic prop-l-enyl ether and racemic benzoate (415)] with the orthoesters (416) or (417) to give the disaccharide (418) [from chiral (414) and acetate (416)] in moderate yield. The disaccharide obtained from racemic (414) contained a high proportion of (418) as a result of asymmetric synthesis. Acidic hydrolysis of (418) gave in low yield (30%) the alcohol (419). 

---