Intramolecular reactions nitrile trapping

Nitrile ylides derived from the photolysis of 1-azirines have also been found to undergo a novel intramolecular 1,1-cycloaddition reaction (75JA3862). Irradiation of (65) gave a 1 1 mixture of azabicyclohexenes (67) and (68). On further irradiation (67) was quantitatively isomerized to (68). Photolysis of (65) in the presence of excess dimethyl acetylenedicar-boxylate resulted in the 1,3-dipolar trapping of the normal nitrile ylide. Under these conditions, the formation of azabicyclohexenes (67) and (68) was entirely suppressed. The photoreaction of the closely related methyl-substituted azirine (65b) gave azabicyclohexene (68b) as the primary photoproduct. The formation of the thermodynamically less favored endo isomer, i.e. (68b), corresponds to a complete inversion of stereochemistry about the TT-system in the cycloaddition process. 

Nitrile ylids generated in this way can be trapped with methanol108 Thus, on irradiation in methanol, the azirine 137 was converted to the methoxy-imine (138). The intramolecular equivalent reaction leading to the oxazoline 139 has also been observed on irradiation of the 2//-azirine (140 R = OH),... 

The most widely used, and often most convenient reagents for such one-pot reactions are sodium hypochlorite (45) or hypobromite (16). These reactions are performed in the presence of an organic base (generally triethylamine) that normally enhances the yield of cycloaddition products (45). This method was employed for many intermolecular reactions (71) and also seems especially suited for intramolecular ones (72-77) as well as for the solid-phase synthesis (78) of 2-isoxazolines. Hypohalite can also be replaced by sodium broruite in combination with a catalytic amount of tri-u-butyltin chloride (79). In a related method, O-tributylstannyl oximes were treated with tert-butyl hypochlorite to produce nitrile oxides that were trapped with aUcenes or alkynes to afford the corresponding isoxazolines or isoxazoles in moderate to good yield (80). 

Intramolecular [4 + 2] cycloaddition reactions are illustrated by thermolysis of the benzocyclo-butene (144) to the tetracyclic system (145), via trapping of a quinodimethane by the nitrile group. 

Fused or spiro sugar oxazolines have been synthesized by treating D-fructopyranose or D-fructofuranose 1,2-0-acetonides with nitriles in triflic acid773 (Scheme 5.73). First the activation of the anomeric center takes place with simultaneous isopropy-lidene cleavage to form the oxocarbenium ion intermediate, which is attacked by the nitrile. The resulting nitrilium ion is then trapped by the hydroxyl group in an intramolecular Ritter-like reaction to yield the final product. 

Bromine-lithium exchange applied to the sulfide obtained from the reaction between 2-fluorobenzonitrile and 2-bromothiophenol promotes an intramolecular attack on the nitrile function. Hydrolysis of the resulting tricyclic lithio-imine produces thioxanthone (Scheme 209). Alternatively, the imine can be trapped with electrophiles... 

Benzylic carbocations are also stabilized by complexation to chromium and a number of interesting reactions have been reported. Again, reaction of the carbocations with nucleophiles occurs from the exo face of the complex, relative to the metal. Carbocations are readily formed by treatment of benzylic alcohols with a strong acid, such as sulfuric acid, tetrafluoroboric acid, or borontrifluoride etherate. The cation can be trapped with water, alcohols, nitriles, and mono-or disubstituted amines to form alcohols, ethers, amides, and di- or trisubstituted amines respectively. Scheme 96 illustrates the formation of a benzylic carbocation followed by intramolecular trapping, resulting in a net inversion of stereochemistry. Benzylic acetates react with trimethyl aluminium introducing a methyl group from the opposite face of the metal. 

Aldoximes 419 are selectively oxidized by (diacetoxyiodo)benzene in methanol containing a catalytic amount of trifluoroacetic acid to give nitrile oxides 420, which can be trapped in situ with olefins in a bimolec-ular or an intramolecular mode to give the synthetically valuable isoxazoline products 421 (Scheme 3.169) [509]. A similar reaction of a-oxo-aldoximes with PhI(OAc)2 affords a-oxo-nitrile oxides, which can be further trapped with norbornene or styrene [510]. 

In contrast to the diverse insertion chemistry of vinylpalladium intermediates discussed in Sects. IV.3 and IV.5, the reactions of vinylpalladium complexes with electrophiles had not been reported until recently. Although a single report on the annulation of the o-mer-curio benzaldehyde with diphenylacetylene into the corresponding indenols and inde-nones catalytic in palladium and stoichiometric in copper had been communicated in 1992, the more synthetically useful protocol for the catalytic version of this type of transformation remained unknown until 1999. In this section the intermolecular carbopalladation of alkynes with aryl halides followed by the intramolecular trapping of the formed vinylpalladium species with ketones, aldehydes, and nitriles will be discussed. 

A ready method for generating oxycaihinyl radicals for radical cyclization reactions involves adding di-/-butyl hyponitrite to refluxing solutions of precursors. For example the 6-bromide 26 gives a radical which is intramolecularly trapped by the nitrile group to pve an imine from which the product 27 is obtained on hydixdysis. ... 

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