Heterocyclics adducts

The first application of microwave irradiation in conjunction with dry media in the generation of nitrile oxide intermediates was reported by Hamelin [29]. In this example, methyl nitroacetate (170) was mixed with a dipolarophile in the presence of catalytic amounts of toluene-p-sulfonic acid (PTSA) (10% weight). Subsequent microwave irradiation led to the formation of the corresponding heterocyclic adducts (Scheme 9.52). Reactions were performed in an open vessel from which water was continuously removed [103], Likewise, irradiation in a domestic oven of a mixture of ethyl chloro(hydroxyimino)acetate (173) and a dipolarophile over alumina led to the same results in only a few minutes (Scheme 9.52) [103]. 

Diaz-Ortiz described the microwave-induced 1,3-dipolar cycloadditions of the me-sitonitrile oxide 10 with aliphatic and aromatic nitriles in solvent-free conditions [99]. The procedure allowed the corresponding heterocyclic adducts, the 1,2,4-oxadia-zoles 187, to be obtained in a domestic oven. The reaction times were shorter and the yields better than those seen with the classical homogeneous reactions (Scheme 9.57). 

The rates of adduct formation follow an inverted trend with respect to that found to the related stabilities. For example, the reaction of MeO with 3,5-dinitropyridine is slightly slower than that with 1,3,5-trinitrobenzene. The higher stability of the heterocyclic adduct 1 results in this case from a relatively low reverse rate. 

If there is stereochemistry in the alkene, it is faithfully reproduced in the heterocyclic adduct as we should expect.for a concerted cycloaddition. 

The reaction of simple 277-azirines with heterocumulenes proceeds to give a wide range of heterocyclic adducts. For example, treating 277-azirine-3-methylacrylate 794 with diphenylketene afforded 5-pyrrolin-2-one 795 in 70% yield (Scheme 193) <1997T7089>. A related reaction occurred using A -sulfonylimines to give 1,2,5-thiodiazoles <1996J(P1)1629>. 

Diels-Alder reactions of heterodienophiles have been known for decades, but only recently has this methodology become widely accepted by the synthetic community. There is enormous diversity in the structural types of compounds which can act as heterodienophiles, and a wide array of heterocyclic adducts can be prepared via these [4 + 2] cycloadditions. It seems clear that hetero Diels-Alder reactions span a range of mechanism from concerted to stepwise ionic processes. In many instances, mechanistic information is totally lacking. The discussion below therefore classifies heterodienophiles by structural rather than mechanistic class. Only the major types of synthetically useful heterodienophiles have been included. Moreover, the significant regio- and stereo-chemical features of the reactions have been exemplified as much as possible using recently reported cases. Other more comprehensive and more specialized reviews should be consulted for older material and more obscure hetero Diels-Alder cycloadditions. 

These intermediates have been intensively studied and characterized by the addition to reactive multiple bonds giving 5-membered heterocyclic adducts . The decomposition of 2,5-diphenyltetrazole follows first order kinetics, with a rate nearly independent of the nature of the solvent . This precludes an interaction with the medium prior to elimination of the nitrogen molecule and confirms that the nitrile imine is an intermediate. Alkylated tetrazoles also undergo elimination of nitrogen on heating. With 2-methyl-5-phenyl-tetrazole however, thermolysis does not occur below about 220 °C and proceeds in competition with a second mode of decomposition which leads to benzonitrile and methylazide , viz. 

A -heterocyclic adducts have also been reported for piperidine, quinoline, isoquinoline, imidi-zoles, dipyridylamines, 2,2-bipyridine, and 1,10-phenanthroline. 

As you might expect, this [3 -1- 2] cycioaddition is a reaction invoiving the HOMO of the alkene and the LUMO of the nitriie oxide so that the ieading interaction that determines the structure of the product is the one in the margin. If there is stereochemistry in the alkene, it is faithfully reproduced in the heterocyclic adduct as is usual for a concerted cycioaddition. 

Very recently, the Chi group disclosed the NHC-catalysed [4 + 3] (ycload-dition of enals and azomethine imines to provide seven membered heterocyclic adducts 132 with excellent diastereoselectivity and enantioselectivity (Scheme 20.56). ... 

Benzannulated enyne isocyanates 524 undergo a cycloaromatization reaction on heating in the presence of PhMe2SiCl to give the heterocyclic adduct 525 in 82 % yield. 

In the reaction of bis-trifluoromethylthioketene with diazomethane, two isomeric heterocyclic adducts 58 (59 %) and 59 (41 %) are obtained, resulting from rearrangement of the initially formed [3+2] cycloadducts... 

The rearrangement of 2-phenyl-3-butyn-2-ol to 3-phenybut-2-en-l-al was examined computationally. The carbocation PhMeC+-C=CH is considered an intermediate or, under some conditions, a transition state. The stepwise Diels-Alder reaction of 1-trimethylsiloxy-1,3-butadiene and 4,6-dinitrobenzofuroxan was studied by computational methods. A stepwise mechanism with a persistent intermediate is supported. However, this intermediate is suggested to be a heterocyclic adduct and not the zwitterionic allyl cation/furoxan anion adduct proposed in the previous studies. 

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