Esters Orthoester

The epoxy ester-orthoester rearrangement occurs in acidic medium through the intermediacy of a dioxycarbenium ion, which forms an orthoester by intramolecular quenching. The mechanism is an example of neighboring group participation of... 

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). 

Acid moieties include formic acid itself, formates and orthoesters, formamide, DMF dimethyl acetal and ethyl diethoxyacetate, acids, acid chlorides and anhydrides, the last including a rare [3,4-oxalate esters, 2-acyl or 2-ethoxycar-bonyl derivatives e.g. 180) are formed. 

Deep fluorinalion of alkanes, ethers, acid fmlides, esters, alkyl chlorides, most ketones, ketals, orthoesters, and combinations of these functional groups produces principally the perfluonnated analogues (Table 2) Chlorine substituents (or chloro groups) usually survive fluorination... 

The orthoester, 2-(triethoxyprop-1-ynyl)quinoxaline (63), gave the regular ester, 2-ethoxycarbonylethynylquinoxaline (64) (TsOH, PhH, 20°C, 1 h 19%) ... 

There are several synthetically important adaptations of the reaction. It can be applied to orthoesters (Section 6.4.2.2) or silyl ketene acetals (Section 6.4.2.3), in which case the products are y,8-unsaturated acids or esters. An analogous reaction using amide... 

Both the exchange and elimination are catalyzed by the addition of a small amount of a weak acid, such as propanoic acid. These reactions are usually conducted at the reflux temperature of the orthoester, which is about 110°C for the trimethyl ester and 140° C for the triethyl ester. Microwave heating has been used and is reported to greatly accelerate orthoester-Claisen rearrangements.232... 

The synthesis93 of N-(2,4-dinitrophenyl)-3-0-(tetra-0-acetyl-/ -D-glu-copyranosyl)-L-threonine methyl ester (131) involved a two-step procedure. First, formation of the intermediate, L-threonine orthoester 130 was achieved by treatment of tetra-O-acetyl-a-D-glucopyranosyl bromide (128) with the methyl ester of N-(2,4-dinitrophenyl)-L-threonine94 (129) under the conditions of the Koenigs-Knorr reaction (see next paragraph), and this was then converted into the L-threonine glycoside 131. 

As in Section 5.06.9.1, the assignments are sometimes arbitrary. Important routes to oxadiazoles, aminooxadiazoles, oxadiazolinones, and oxadiazolinethiones involving the reaction of hydrazides RCONHNH2 with carboxylic acids, acyl chlorides, alkyl esters, or trialkyl orthoesters are described in Section 5.06.9.2.1, reactions with carbon disulfide... 

Compared to the well-known OBO esters [81], the ABO esters are more stable towards protic acids but less stable towards the Lewis acid Cp2ZrCl2/AgC104, which isomerizes the ABO orthoester to a tetrahydrofuranyl ester. Selective deprotection is therefore possible (Scheme 8.41). 

Pyrrolo[l,2-rf [l,2,4]triazinones 21 were synthesized from methyl ester of /ra j-4-hydroxy-L-proline 72. The synthetic route involved formation of hydrazones followed by cyclisation with orthoesters <1998BMC349>. Similar reactions have been developed with 3-benzylindole-2-carbohydrazides 73 in reaction with triethyl orthoformate, giving the corresponding ring systems indolo[l,2-r][ 1,2,4]triazin-4-oncs 74 <2004JHC7>. 

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]. 

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